Kidney/Renal Cancer

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A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SNS-101 (Anti VISTA) as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors


Condition: Solid Tumor, Adult, Advanced Solid Tumor, Head and Neck Cancer, Breast Cancer, Colon Cancer, Pancreatic Cancer, Gastric Cancer, Esophageal Cancer, Prostate Cancer, Uterine Cancer, Cervix Cancer, Ovarian Cancer, Kidney Cancer, Bladder Cancer, Thyroid Cancer, Melanoma, Sarcoma, Advanced Cancer, Metastatic Cancer, Refractory Cancer, Non Small Cell Lung Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05864144

Sponsor: Sensei Biotherapeutics, Inc.

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Key Inclusion Criteria:

  • Histologically or cytologically documented locally advanced, unresectable or metastatic solid tumor.
  • Having received and failed or was intolerant to standard of care for advanced disease or not eligible for standard of care therapy with the following tumor types for patients in Phase 1 dose expansion cohorts: 1. Microsatellite Stable (MSS) CRC (both monotherapy and combination cohorts); no more than 3 lines of prior systemic therapy for metastatic disease. 2. H&N cancer (combination cohort only); no more than 2 lines of prior systemic therapy for metastatic disease. 3. Melanoma (combination cohort only); no more than 3 lines of prior systemic therapy for metastatic disease, including at least 1 prior treatment with a BRAF inhibitor for patients with a BRAF mutation. 4. NSCLC (combination cohort only); no more than 2 lines of prior systemic therapy for metastatic disease, including at least 1 prior treatment with a targeted therapy for patients with a mutation such as EGFR, ALK, KRAS, or RET. 5. Patients with H&N cancer, melanoma, and NSCLC must not have demonstrated primary refractory disease to a prior PD-1/PD-L1 agent where the best response to that therapy was progressive disease. Additional tumor types and doses may be considered.
  • Measurable disease.
  • ECOG performance status 0 or 1.
  • Life expectancy of ≥ 3 months.
  • Willing to provide pre-treatment (archival or fresh) and on-treatment tumor biopsy samples.
  • Adequate organ function
  • Women of childbearing potential and fertile males with WOCBP partners must use highly effective contraception during the study and for 180 days after the study. Patients must agree not to donate eggs (ova, oocytes) or sperm during the study.

Key Exclusion Criteria:

  • Use of anti-PD-1/PD-L1 targeting monoclonal antibody therapy, monoclonal antibody therapy, chemotherapy, biologic, investigational, or radiotherapy within 2 weeks of Cycle 1 Day 1.
  • Clinically significant unresolved toxicities from prior anticancer therapy.
  • Grade 3 or higher immune-related adverse event on prior PD-1/PD-L1 blockade or prior agents targeting stimulatory or co-inhibitory T cell receptor.
  • Known other previous/current malignancy requiring treatment within ≤ 2 years except for limited disease treated with curative intent, such as carcinoma in situ, squamous or basal cell skin carcinoma, or superficial bladder carcinoma.
  • Known asymptomatic or symptomatic brain metastasis or leptomeningeal disease.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  • Women who are pregnant or breastfeeding.

View trial on ClinicalTrials.gov


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A Phase 1/2 Open-label Trial of KVA12123 Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors


Condition: Cancer, Solid Tumor, Melanoma, Carcinoma, Sarcoma, Lung Cancer, Prostate Cancer, Breast Cancer, Colo-rectal Cancer, Uterine Cancer, Pancreatic Cancer, Gastric Cancer, Esophageal Cancer, Thyroid Cancer, Ovarian Cancer, Kidney Cancer, Head and Neck Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05708950

Sponsor: Kineta Inc.

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. Willing and able to provide informed consent.
  2. Be at least 18 years of age at the time of consent.
  3. Has histologically or cytologically confirmed, locally advanced or metastatic solid tumor that has progressed or was non-responsive to standard of care therapy and for which no available curative therapy exists.
  4. Has expected survival ≥16 weeks.
  5. Presence of measurable disease by iRECIST.
  6. Has an ECOG performance status score of 0 or
  7. Has adequate organ function within 10 days prior to the start of study treatment.
  8. Has normal thyroid function or hypothyroid with stable supplementation.
  9. Has consented to the collection of archival tissue prior to study treatment initiation.
  10. Participants with prior exposure to systemic anticancer therapy including investigational agents following a 4-week washout period are eligible. Participants with prior small molecule targeted therapy or other short half-life drugs are eligible following a 2-week washout period.
  11. Participants having prior curative radiation therapy completed 2 weeks prior to study drug administration or prior palliative radiation therapy to non-CNS disease completed at least 1 week prior to study drug administration are eligible.
  12. HIV-infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease.
  13. Participants with a history of HBV infection having durable HBsAg loss and undetectable serum HBV DNA no longer requiring treatment are eligible.
  14. Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening and participants have completed curative antiviral therapy.
  15. Post-menopausal women and surgically sterile men and women are permitted.
  16. Patients of childbearing potential are permitted to participate under the following conditions:
  17. Must have negative urine pregnancy test result within 72 hrs prior to the first dose of any study drug
  18. Must agree not to become pregnant during the study and for 120 days after the final dose of any study drug
  19. Must agree not to breastfeed or donate ova, starting at time of informed consent and continuing through 120 days after the final dose of any study drug
  20. If sexually active in a way that could lead to pregnancy, must consistently use 2 acceptable methods of birth control (contraception), at least 1 of which must be highly effective starting at time of informed consent and continuing throughout the study and for 120 days after the final dose of any study drug.
  21. Patients who can father children are permitted to participate under the following conditions:
  22. Must agree not to donate sperm starting at the time of informed consent and continuing throughout the study period and for 120 days after the final dose of any study drug
  23. If sexually active with a person of childbearing potential in a way that could lead to pregnancy, must consistently use 2 acceptable methods of birth control (contraception), at least 1 of which must be highly effective starting at the time of informed consent and continuing throughout the study and for 120 days after the final dose of any study drug
  24. If sexually active with a person who is pregnant or breastfeeding, must consistently use a condom starting at time of informed consent and continuing throughout the study and for 120 days after the final dose of any study drug.
  25. Must be willing and able to comply with the trial procedures and the follow-up schedule.

Exclusion Criteria:

  1. Untreated CNS metastatic disease, leptomeningeal disease, or cord compression.
  2. Concurrent cancer other than disease under study requiring systemic treatment. Participants with basal cell or squamous cell skin cancer treated with curative intent, carcinoma in-situ of the cervix or breast treated with curative intent, RAI stage 0 Chronic Lymphocytic Leukemia, monoclonal gammopathy of undetermined significance, superficial bladder cancer or very low and low risk prostate cancer (localized Gleason score ≤ 6) under active surveillance are eligible.
  3. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
  4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg QD of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
  5. History of (non-infectious) pneumonitis/interstitial lung disease (ILD) that required steroids or current pneumonitis/ILD.
  6. Prior treatment with VISTA-targeted therapy.
  7. Prior history of allogeneic, solid organ or stem cell transplant, or adoptive T-cell transplant.
  8. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, LAG-3, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE).
  9. Active known or suspected autoimmune disease that has required systemic treatment within the past year. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  10. Prior systemic anticancer therapy, including investigational agents, within 4 weeks of treatment. Participants with prior small molecule targeted therapy or other short half-life drugs are eligible following a 2-week washout period.
  11. Has received prior radiation therapy within 2 weeks of start of study treatment or has a history of radiation pneumonitis.
  12. Has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study treatment.
  13. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
  14. Any requirement for daily supplemental oxygen.
  15. Any condition requiring systemic treatment with corticosteroids (>10 mg QD prednisone equivalents) or other immunosuppressive medications within 14 days before the first dose of study drug.
  16. Serious or poorly controlled cardiovascular disease.
  17. Chronic hepatitis B or C.
  18. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
  19. Has an active infection requiring systemic therapy.
  20. Known active or latent tuberculosis.
  21. If the participant had major surgery, must have recovered adequately from the procedure and/or any complications.
  22. Toxicities arising from prior cancer therapy that have not resolved to Grade 1 or baseline.
  23. Red blood cell or platelet infusion within the preceding 2 weeks.
  24. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
  25. Known hypersensitivity to any excipient contained in the drug formulation of KVA121
  26. Any significant history of drug allergy as assessed by the investigator.
  27. Positive urine pregnancy test within 72 hrs of study drug administration.
  28. Participants who are breastfeeding, pregnant, or planning to become pregnant from time of informed consent until at least 120 days after final dose of study drug.
  29. Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study.
  30. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
  31. Inability to comply with study procedures.

View trial on ClinicalTrials.gov


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Randomized Phase II Stereotactic Ablative Radiation Therapy (SABR) for Metastatic Unresected Renal Cell Carcinoma (RCC) Receiving Immunotherapy (SAMURAI)


Condition: Metastatic Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Unresectable Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05327686

Sponsor: NRG Oncology

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration
  • Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:
  • History/physical examination within 45 days prior to registration
  • CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration
  • Patients must have IMDC intermediate (1-2 factors) or poor risk disease (>= 3 factors)
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor
  • Patient not recommended for or refused immediate cytoreductive nephrectomy
  • Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen
  • Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging
  • Age >= 18
  • Karnofsky performance status >= 60 within 45 days prior to registration
  • Hemoglobin >= 8 g/dL (transfusions are allowed) (within 45 days prior to registration)
  • Platelet count >= 50,000/mm^3 (within 45 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (within 45 days prior to registration)
  • Calculated (Calc.) creatinine clearance >= 30 mL/min (within 45 days prior to registration)
  • For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) (within 45 days prior to registration)
  • Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =< 3 x upper limit of normal (ULN) or < 5 x ULN if hepatic metastases present (within 45 days prior to registration)
  • Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
  • The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

  • Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment
  • Patients with untreated or unstable brain metastases or cranial epidural disease
  • Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
  • Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor
  • Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated > 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration)
  • Severe, active comorbidity defined as follows:
  • Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
  • Active tuberculosis (purified protein derivative [PPD] response without active tuberculosis [TB] is allowed)
  • Uncontrolled hypertension (systolic blood pressure [BP] > 190 mmHg or diastolic BP > 110 mmHg)
  • Major surgery requiring hospital admission ≤ 28 days prior to registration.
  • Any serious (requiring hospital stay or long-term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration
  • Any arterial thrombotic (ST elevation myocardial infarction [STEMI], non-ST elevation myocardial infarction [NSTEMI], cerebrovascular accident [CVA], etc) events within 180 days prior to registration
  • Active New York (NY) Heart Association class 3-4 heart failure symptoms
  • Moderate or severe hepatic impairment (Child-Pugh B or C)
  • Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis > 30 days prior to registration is allowed)
  • Unstable cardiac arrhythmia within 180 days prior to registration
  • History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration
  • History of or active inflammatory bowel disease
  • Malabsorption syndrome within 45 days prior to registration
  • Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =< 45 days prior to registration

View trial on ClinicalTrials.gov


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A Phase I, Open-label, Multi-center Study of KFA115 as a Single Agent and in Combination With Pembrolizumab in Patients With Select Advanced Cancers


Condition: Carcinoma, Non-Small-Cell Lung, Cutaneous Melanoma, Carcinoma, Renal Cell, Carcinoma, Ovarian Epithelial, Nasopharyngeal Carcinoma, Carcinoma, Thymic, Anal Cancer, Mesothelioma, Esophagogastric Cancer, High Microsatellite Instability Colorectal Carcinoma, Squamous Cell Carcinoma of Head and Neck, Triple Negative Breast Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05544929

Sponsor: Novartis Pharmaceuticals

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Non-small cell lung cancer with historic PD-L1 ≥ 1%, as determined locally using a clinically accepted assay. Patients must have experienced benefit from previous anti-PD(L)1-containing therapy for at least 4 months based on investigator-assessed disease stability or response prior to developing documented disease progression. Patients must have also received prior platinum-based chemotherapy, either in combination or in sequence with anti-PD-(L)1, unless patient was ineligible to receive such treatment.
  • Renal cell carcinoma, clear cell histology, previously treated with anti-PD(L)1-containing therapy and a VEGF targeted therapy as monotherapy or in combination. Patients should have documented disease progression following anti-PD(L)1-containing therapy.
  • Cutaneous melanoma, previously treated with anti-PD(L)1-containing therapy. Patients should have documented disease progression following anti-PD(L)1-containing therapy. Patients with BRAF V600-mutant melanoma must have also received prior therapy with a BRAF V600 inhibitor, with or without a MEK inhibitor.
  • Ovarian cancer, high-grade serous histology, naïve to anti-PD(L)1 therapy, must have received one prior systemic therapy in platinum-resistant setting.
  • Nasopharyngeal carcinoma, non-keratinizing locally advanced recurrent or metastatic. Depending on the study arm, patients may be naïve to anti-PD(L)1 therapy, or previously treated with platinum-based chemotherapy with or without anti-PD-(L)1.
  • Locally advanced unresectable or metastatic triple negative breast cancer, ovarian cancer (high-grade serous histology), anal cancer (squamous), MSI-H CRC, esophagogastric cancer, mesothelioma, and HNSCC.
  • Locally advanced unresectable or metastatic anal cancer (squamous), thymic carcinoma, MSI-H CRC, esophagogastric cancer, mesothelioma, and HNSCC, all naïve to anti-PD(L)1 therapy and for whom anti PD(L)1 therapy is not available.
  • Triple negative breast cancer with historic PD-L1 CPS ≥ 1%, must have received at least one line of chemotherapy. Exclusion Criteria:
  • Impaired cardiac function or clinically significant cardiac disease.
  • Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of study.
  • History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients.
  • Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur may be considered. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
  • Any evidence of interstitial lung disease (ILD) or pneumonitis, or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
  • Patients who discontinued prior anti-PD-(L)1 therapy due to an anti-PD-(L)1-related toxicity (applicable to the KFA115 in combination with pembrolizumab treatment arms).
  • Patients with symptomatic peripheral neuropathy limiting instrumental activities of daily living. Other protocol-defined inclusion/

Exclusion Criteria:

  • Impaired cardiac function or clinically significant cardiac disease.
  • Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of study.
  • History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients.
  • Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur may be considered. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
  • Any evidence of interstitial lung disease (ILD) or pneumonitis, or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
  • Patients who discontinued prior anti-PD-(L)1 therapy due to an anti-PD-(L)1-related toxicity (applicable to the KFA115 in combination with pembrolizumab treatment arms).
  • Patients with symptomatic peripheral neuropathy limiting instrumental activities of daily living. Other protocol-defined inclusion/exclusion criteria may apply

View trial on ClinicalTrials.gov


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A Phase I/Ib, Open-label, Multi-center, Study of QEQ278 in Patients With Advanced Solid Tumors


Condition: Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Esophageal Squamous Cell Carcinoma, Squamous Cell Carcinoma of Head and Neck

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05462873

Sponsor: Novartis Pharmaceuticals

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Signed informed consent must be obtained prior to participation in the study.
  • Adult men and women ≥ 18 years of age.
  • Histologically confirmed and documented advanced malignancies (locally advanced malignancies, non-curable by surgery or radiotherapy and metastatic disease). Disease must be measurable, including presence of at least one measurable lesion, as determined by RECIST v1.1.
  • In the opinion of the treating investigator, patients must have received, but are not benefitting from standard therapies, be intolerant or ineligible to receive such therapy, or have no standard therapy option for the respective disease types (diseases listed below), as well as any other therapies deemed to be standard by local/institutional standard.
  • Non-small cell lung cancer
  • Esophageal squamous cell carcinoma
  • Renal cell carcinoma
  • HPV-associated head and neck squamous cell carcinoma
  • Must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. The patient must be willing to undergo a new tumor biopsy at screening and during treatment. Exclusion Criteria:
  • Active previously documented or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur should not be excluded. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
  • Patients with a history of or current interstitial lung disease or pneumonitis ≥ Grade 2.
  • Patients who discontinued prior anti-PD-1 therapy due to an anti-PD-1-related toxicity
  • Clinically significant cardiac disease or risk factors at screening
  • Insufficient bone marrow function at screening:
  • Infections:
  • Known history of testing positive for Human Immunodeficiency Virus infection.
  • Active Hepatitis B and / or Hepatitis C.
  • Active, documented COVID-19 infection
  • Known history of tuberculosis
  • Any serious uncontrolled infection (acute or chronic).
  • Systemic chronic steroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy, other than replacement-dose steroids in the setting of adrenal insufficiency, within 7 days of the first dose of study treatment. Topical, inhaled, and ophthalmic steroids are allowed. Other protocol-defined inclusion/

Exclusion Criteria:

  • Active previously documented or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur should not be excluded. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
  • Patients with a history of or current interstitial lung disease or pneumonitis ≥ Grade 2.
  • Patients who discontinued prior anti-PD-1 therapy due to an anti-PD-1-related toxicity
  • Clinically significant cardiac disease or risk factors at screening
  • Insufficient bone marrow function at screening:
  • Infections:
  • Known history of testing positive for Human Immunodeficiency Virus infection.
  • Active Hepatitis B and / or Hepatitis C.
  • Active, documented COVID-19 infection
  • Known history of tuberculosis
  • Any serious uncontrolled infection (acute or chronic).
  • Systemic chronic steroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy, other than replacement-dose steroids in the setting of adrenal insufficiency, within 7 days of the first dose of study treatment. Topical, inhaled, and ophthalmic steroids are allowed. Other protocol-defined inclusion/exclusion criteria may apply.

View trial on ClinicalTrials.gov


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A Phase 1/1b Study of CHS-388 (Formerly Known as SRF388) in Patients With Advanced Solid Tumors


Condition: Advanced Solid Tumor, Clear Cell Renal Cell Carcinoma, Hepatocellular Carcinoma, Non-small Cell Lung Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04374877

Sponsor: Coherus Biosciences, Inc.

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • ≥ 18 years of age
  • Locally advanced or metastatic (Stage IV) solid tumor that has progressed during or after standard therapy, and for whom no available therapies are appropriate (based on investigator judgment)
  • Patients in Part B with advanced or metastatic ccRCC, HCC, or NSCLC must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Patients with HCC in Part B must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
  • Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC1) Stage B (not eligible for transcatheter arterial chemoembolization [TACE]) or Stage C
  • For patients in Part B with ccRCC, demonstrated progressive disease (PD) during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with regimen(s) that have included a vascular endothelial growth factor (VEGF)-targeted agent and an immune checkpoint inhibitor. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
  • For patients in Part B with HCC, demonstrated PD during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with a VEGF-targeted agent. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
  • For Part B patients in the tumor biopsy subsets only, must have tumor tissue that is accessible for pretreatment and on-treatment tumor biopsy in the opinion of the Investigator and be willing to undergo pretreatment and on-treatment biopsies per protocol
  • Serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula or serum creatinine ≤ 2.0 x the upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN if elevated because of Gilbert's syndrome and ≤ 2 x ULN for patients with HCC or patients with known liver metastases)
  • Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) < 2.5 x ULN (< 5 x ULN if liver metastasis or for patients with HCC)
  • For patients with HCC, Child-Pugh class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
  • Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1.0 x 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 x 109/L. For patients with HCC, platelet count ≥ 75 x 109/L without transfusion
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patients with NSCLC must have histologically confirmed locally advanced and/or metastatic Stage IV NSCLC
  • Patients with NSCLC must have demonstrated progressive disease during or after the most recent treatment regimen Part C Abbreviated Inclusion Criteria:
  • ≥ 18 years of age
  • Advanced RCC of any histology or advanced HCC previously treated with at least one systemic anticancer therapy OR histologically or cytologically confirmed metastatic or unresectable adenocarcinoma or squamous cell NSCLC
  • Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC) Stage B (not eligible for transcatheter arterial chemoembolization) or Stage C
  • At least 1 measurable lesion per RECIST 1.1
  • Patients with HCC must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
  • ECOG performance status of 0-1
  • ANC ≥1500/µL (1.5 x 109/L)
  • Platelets ≥100 000/µL (≥ 100 x 109/L)
  • Hemoglobin for participants with RCC: ≥9.0 g/dL; for participants with HCC: ≥8.5 g/dL
  • Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
  • Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
  • AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
  • International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • For patients with HCC, Child-Pugh Class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
  • Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of CHS-388 or 120 days after the last dose of pembrolizumab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section. Part C Abbreviated Inclusion Criteria Specific to Patients with RCC or HCC from Part A or Part B:
  • Progressed on CHS-388 by RECIST 1.1
  • Did not experience prior Grade ≥ 3 toxicity related to CHS-388
  • Willingness to undergo pretreatment core or excisional biopsy if deemed safe and tumor is accessible, in the opinion of the Investigator
  • Has received no systemic anticancer therapies between CHS-388 doses Part C Abbreviated Inclusion Criteria specific to NSCLC Patients:
  • No more than 3 prior lines of systemic therapy for unresectable or metastatic disease with prior radiologic progression on or following platinum-based chemotherapy and prior anti-PD-(L)1 therapy whether given alone or in combination Part A and Part B Abbreviated Exclusion Criteria:
  • Previously received an anti-IL-27 antibody or anti-IL-27 targeted therapy
  • For patients in Part B with renal cell carcinoma (RCC), non-clear cell RCC histology
  • For patients with HCC, known fibrolamellar or mixed hepatocellular cholangiocarcinoma
  • History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
  • Major surgery within 4 weeks prior to Screening
  • Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study Part C Abbreviated Exclusion Criteria:
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
  • Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received CHS-388 in Part A or Part B)
  • No prior systemic therapy for unresectable or metastatic disease
  • Received > 4 prior systemic regimens for unresectable or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
  • For patients with HCC, fibrolamellar histology or mixed hepatocellular cholangiocarcinoma
  • For patients with HCC, moderate or severe ascites
  • For patients with HCC, inability to undergo disease evaluation with triphasic computed tomography or magnetic resonance imaging because of contrast allergy or other contraindication
  • For patients with HCC, imaging findings consistent with ≥ 50% liver occupation by HCC tumors
  • History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
  • Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration
  • Prior autologous stem cell transplant ≤ 3 months before the first dose
  • Prior allogeneic hematopoietic cell transplant within 6 months of the first dose or with a history of or current clinical Graft-Versus-Host Disease
  • Has had an allogenic tissue/solid organ transplant
  • Other unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study Part D Abbreviated Inclusion Criteria
  • ≥ 18 years of age
  • Histologically or cytologically confirmed metastatic or unresectable adenocarcinoma or squamous cell NSCLC
  • No more than 3 prior lines of systemic therapy for unresectable or metastatic disease with prior radiologic progression on or following platinum-based chemotherapy and prior anti-PD-(L)1 therapy whether given alone or in combination
  • At least 1 measurable lesion per RECIST 1.1
  • ECOG performance status of 0-1
  • ANC ≥1500/µL (1.5 x 109/L)
  • Platelets ≥100 000/µL (≥ 100 x 109/L)
  • Hemoglobin for participants with RCC: ≥9.0 g/dL
  • Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
  • Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
  • AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
  • International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of CHS-388 or 180 days after the last dose of toripalimab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section. Part D Abbreviated

Exclusion Criteria:

  • Previously received an anti-IL-27 antibody or anti-IL-27 targeted therapy
  • For patients in Part B with renal cell carcinoma (RCC), non-clear cell RCC histology
  • For patients with HCC, known fibrolamellar or mixed hepatocellular cholangiocarcinoma
  • History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
  • Major surgery within 4 weeks prior to Screening
  • Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study Part C Abbreviated Exclusion Criteria:
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
  • Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received CHS-388 in Part A or Part B)
  • No prior systemic therapy for unresectable or metastatic disease
  • Received > 4 prior systemic regimens for unresectable or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
  • For patients with HCC, fibrolamellar histology or mixed hepatocellular cholangiocarcinoma
  • For patients with HCC, moderate or severe ascites
  • For patients with HCC, inability to undergo disease evaluation with triphasic computed tomography or magnetic resonance imaging because of contrast allergy or other contraindication
  • For patients with HCC, imaging findings consistent with ≥ 50% liver occupation by HCC tumors
  • History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
  • Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration
  • Prior autologous stem cell transplant ≤ 3 months before the first dose
  • Prior allogeneic hematopoietic cell transplant within 6 months of the first dose or with a history of or current clinical Graft-Versus-Host Disease
  • Has had an allogenic tissue/solid organ transplant
  • Other unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study Part D Abbreviated Inclusion Criteria
  • ≥ 18 years of age
  • Histologically or cytologically confirmed metastatic or unresectable adenocarcinoma or squamous cell NSCLC
  • No more than 3 prior lines of systemic therapy for unresectable or metastatic disease with prior radiologic progression on or following platinum-based chemotherapy and prior anti-PD-(L)1 therapy whether given alone or in combination
  • At least 1 measurable lesion per RECIST 1.1
  • ECOG performance status of 0-1
  • ANC ≥1500/µL (1.5 x 109/L)
  • Platelets ≥100 000/µL (≥ 100 x 109/L)
  • Hemoglobin for participants with RCC: ≥9.0 g/dL
  • Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
  • Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
  • AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
  • International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of CHS-388 or 180 days after the last dose of toripalimab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section. Part D Abbreviated Exclusion Criteria:
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
  • Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received CHS-388 in Part A or Part B)
  • No prior systemic therapy for unresectable or metastatic disease
  • Received > 4 prior systemic regimens for unresectable or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a ≥ Grade 3 irAE. because of contrast allergy or other contraindication
  • History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
  • Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration
  • Prior autologous stem cell transplant ≤ 3 months before the first dose
  • Prior allogeneic hematopoietic cell transplant within 6 months of the first dose or with a history of or current clinical Graft-Versus-Host Disease
  • Has had an allogenic tissue/solid organ transplant
  • Other unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study

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An Open-label, Phase 1, First-in-human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Maximum Tolerated or Administered Dose, Pharmacokinetics, Pharmacodynamics, and Tumor Response Profile of the Diacylglycerol Kinase Zeta Inhibitor (DGKzi) BAY 2965501 as Monotherapy, and in Combination, in Participants With Advanced Solid Tumors


Condition: Advanced Solid Tumors

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05614102

Sponsor: Bayer

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Have measurable disease per Response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) as assessed by the local site investigator.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Participants with histologically confirmed diagnosis of a solid tumor (specifications for the different parts of the study below) will be enrolled onto this study: • Dose escalation: All solid cancers, except primary central nervous system cancers
  • The following tumor types will be recruited to the monotherapy expansion cohorts:
  • Non-small cell lung cancer (NSCLC)
  • Gastric/Gastroesophageal Junction (GEJ) adenocarcinoma
  • The following tumor types will be recruited to the BAY 2965501 and pembrolizumab combination expansion cohorts:
  • NSCLC: participants with tumors that are TPS score ≥50% PDL-1 high (based on local historical testing) and are eligible for standard of care anti-PD(L)-1 monotherapy in the first line incurable treatment setting.
  • NSCLC
  • Gastric/GEJ adenocarcinoma

Exclusion Criteria:

  • Previous therapy with a DGK inhibitor is prohibited for monotherapy cohorts (participants previously treated with BAY 2965501 or BAY 2862789 must have progressed on that DGK inhibitor (and not discontinued for toxicity) to be eligible for combination).
  • Has received a prior therapeutic regimen containing an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or an agent directed to another co-stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher infusion-related adverse event (irAE).
  • Participants with new brain metastases on screening brain MRI/CT. Previously treated brain metastases that are progressive at screening compared to a brain MRI/CT at least 6 weeks earlier are also excluded. Participants with known previously treated brain metastases, which are radiologically stable compared to a CT/MRI scan at least 6 weeks earlier, clinically stable and without the requirement of steroid treatment for at least 14 days prior to the first dose of study treatment may be eligible.
  • Primary central nervous system malignancy or presence of leptomeningeal disease (i.e., positive cerebrospinal fluid cytology or unequivocal radiological or clinical evidence of leptomeningeal involvement).
  • Participants with gastrointestinal conditions that may compromise oral absorption such as short bowel syndrome or active tumor-related bowel obstruction with ongoing symptoms compromising absorption over last 6 months.

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A Multicenter, Open-label, Randomized, Phase 1/2 Study of Belzutifan in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma


Condition: Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05468697

Sponsor: Merck Sharp & Dohme LLC

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Has a histologically confirmed diagnosis of unresectable Stage IV (per American Joint Committee on Cancer [AJCC], 8th Edition) RCC with clear-cell component
  • Has had disease progression on or after having received at least 2 systemic treatments for unresectable Stage IV RCC with prior anti-programmed cell death 1 ligand 1 (PD-1/L1) and a vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) in sequence or in combination
  • Has measurable disease per RECIST 1.1 as assessed by the investigator and verified by blinded independent central review (BICR)
  • Has recovered from all AEs due to previous therapies

Exclusion Criteria:

  • Has hypoxia, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
  • Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has clinically significant cardiac disease
  • Has moderate to severe hepatic impairment
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has a history of hepatitis B (HBV) or known active hepatitis C (HCV) infection
  • Has received prior treatment of belzutifan or palbociclib
  • Has received prior radiotherapy ≤2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids
  • Has had major surgery ≤3 weeks prior to first dose of study intervention
  • Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin [EPO]) ≤28 days prior to the first dose of study intervention

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Phase 1/2 Open Label Dose-escalation and Expansion Trial of NKT2152 an Orally Administered HIF2α Inhibitor to Investigate Safety Pharmacokinetics Pharmacodynamics and Clinical Activity in Patients With Advanced Clear Cell Renal Cell Carcinoma


Condition: ccRCC, Clear Cell Renal Cell Carcinoma, Kidney Cancer, Kidney Neoplasms, Renal Cancer, Renal Neoplasms, Recurrent Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma, Refractory Renal Cell Carcinoma, Advanced Renal Cell Carcinoma, Hypoxia, Renal Cell Carcinoma, Hypoxia Inducible Factor (HIF), HIF2α Inhibitor, Hypoxia Inducible Factor 2 Alpha (HIF-2 Alpha), Hypoxia Inducible Factor 2α (HIF-2α), Clear Cell

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05119335

Sponsor: NiKang Therapeutics, Inc.

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Criteria: Patients must meet all of the following criteria to be enrolled in this study. 1. Has the ability to understand and willingness to sign a written informed consent form before the performance of any study procedures 2. Has locally advanced or metastatic ccRCC and has progressed during treatment, are relapsed, refractory and not amenable to curative therapy or standard therapy and has progressed during treatment with at least 1 prior therapeutic regimen 3. Must have measurable disease per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) 4. Is of age ≥ 18 years 5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 6. Has a life expectancy of ≥ 3 months 7. Has adequate organ function defined as follows: 1. Bone marrow: ANC ≥ 1.0 × 10^9/L; Hgb level ≥ 10 g/dL without transfusion or erythropoietin support within 2 weeks prior to first dose; platelet count ≥ 75,000/μL 2. Hepatic: transaminase levels (AST/ALT) ≤ 2.5 × ULN (≤ 5 × ULN if liver metastases is present); total bilirubin (TBILI) ≤ 1.5 × ULN in the absence of Gilbert's disease 3. Renal: serum creatinine level ≤ 2.0 × ULN or calculated creatinine clearance (CrCL) ≥ 40 mL/min (Cockcroft-Gault formula) 8. If a female patient of child-bearing potential, has a negative serum pregnancy test result within 7 days before first study drug administration 9. If a female patient, must be surgically sterile, must be post-menopausal, or must agree to use physician-approved method of birth control during screening, during the study, and for a minimum of 6 months after the last study drug administration; or if a male patient with a female partner, must agree to use physician-approved method of birth control during screening, during the study, and for a minimum of 6 months after the last study drug administration 10. Female patients of childbearing potential must meet all of the following criteria: 1. Not pregnant (negative serum pregnancy test during Screening) 2. Not breast feeding 3. Willing to use a protocol-recommended method of contraception or to abstain from heterosexual intercourse from the start of treatment or until at least 6 months after the last dose of treatment. Note: A female patient is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone levels within the institutional laboratory postmenopausal range and a negative serum or urine beta human chorionic gonadotropin); or is menopausal (amenorrhea for 12 months). 11. Male patients who can father a child must meet all of the following criteria: 1. Willing to use a protocol-recommended method of contraception or to abstain from heterosexual intercourse with females of childbearing potential from the start of treatment until at least 6 months after the last dose of treatment, and 2. Willing to refrain from sperm donation from the start of treatment until at least 6 months after the last dose of treatment. Note: A male patient is considered able to father a child unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy. 12. Able to swallow oral medications. 13. Ambulatory subjects need to take a six-minute walk test. Walking distance needs to be at least 400 meters and the change of oxygen saturation needs to be within 5% range. Patients will be excluded from this study if they meet any of the following criteria. 1. Known symptomatic brain metastases requiring > 10 mg/day of prednisone (or its equivalent). Patients with previously diagnosed brain metastases are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to the start of NKT2152 treatment, fulfill the above steroid requirement for these metastases, and are neurologically stable based on central nervous system imaging ≥ 4 weeks after CNS-directed treatment. 2. Having one or more of the following conditions: 1. A pulse oximetry reading less than 95% at screening; 2. Any current requirement for intermittent or chronic supplemental oxygen; 3. Any chronic lung condition which has required supplemental oxygen in the past; 4. Evidence of impending airway compromise (such as endobronchial tumor, lymphangitic spread, significant extrinsic compression of major airway) per investigator; 5. Ascites requiring drainage within 28 days prior to W1D1 3. History of another malignancy except for the following: adequately treated local basal cell or squamous carcinoma of the skin, in situ cervical cancer, adequately treated papillary noninvasive bladder cancer, other adequately treated Stage 1 or Stage 2 cancers currently in complete remission, or any other cancer that has been in complete remission for ≥ 2 years 4. Has failed to recover from the effects of prior anticancer therapy to baseline level or Grade 1 severity (except for alopecia) per NCI CTCAE; patients with treatable adverse effects such as hypothyroidism or hypertension may be enrolled if the adverse effect is controlled with treatment 5. Significant cardiovascular disease, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 6 months prior to start of NKT2152 treatment; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy, symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; ≥ Grade 3 hypertension (diastolic blood pressure ≥ 100 mmHg or systolic blood pressure ≥160 mmHg) despite adequate use of anti-hypertensives; or history of congenital prolonged QT syndrome or repeated demonstration of a QTc interval > 480 ms; ejection fraction < 40%; clinically significant pericardial or pleural effusion in the opinion of the investigator. 6. Has received prior investigational therapy or standard therapy within 5 half-lives of the agent or 4 weeks before the first administration of study drug, whichever is shorter 7. Has a bleeding diathesis or coagulopathy 8. Deep vein thrombosis (DVT)/pulmonary embolism are allowed as long as patient is not symptomatic and received 2 weeks or more of adequate anticoagulation 9. Has manifestations of malabsorption due to prior gastrointestinal (GI) surgery or GI disease 10. Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results 11. Has had major surgery within 4 weeks before first study drug administration; the following procedures are not considered to be major surgeries: thoracentesis, port placement, laparoscopy, thoracoscopy, bronchoscopy, endoscopic or ultrasonographic procedures, mediastinoscopy, skin biopsy, incisional biopsy, image-guided biopsy for diagnostic purposes, and routine dental procedures 12. Has known human immunodeficiency virus (HIV) 13. Has an active infection requiring systemic treatment 14. Is actively participating in another therapeutic clinical trial

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A Multicenter, Double-blind, Randomized Phase 3 Study to Compare the Efficacy and Safety of Belzutifan (MK-6482) Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in the Adjuvant Treatment of Clear Cell Renal Cell Carcinoma (ccRCC) Post Nephrectomy (MK-6482-022)


Condition: Carcinoma, Renal Cell

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05239728

Sponsor: Merck Sharp & Dohme LLC

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Exclusion Criteria:

  1. include but are not limited to the following:

Inclusion Criteria:

  • Has a histologically or cytologically confirmed diagnosis of RCC with clear cell component per American Joint Committee on Cancer (AJCC) (8th Edition), with or without sarcomatoid features
  • Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node metastasis and tumor grading: 1. Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, any grade, N0, M0 2. High risk RCC: pT4, any Grade N0, M0; pT any stage, any Grade, N+, M0 3. M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ≤2 years from nephrectomy (metachronous)
  • Has undergone complete resection of the primary tumor (partial or radical nephrectomy) and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants
  • Must have undergone a nephrectomy and/or metastasectomy ≤12 weeks prior to randomization
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days before randomization.
  • Male participants must agree to continue contraception at least 7 days after the last dose of belzutifan/placebo
  • Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of pembrolizumab or at least 30 days after last dose of belzutifan/placebo, whichever occurs last
  • Has adequate organ function Exclusion Criteria:
  • Has had a major surgery, other than nephrectomy plus resection of preexisting metastases for M1 NED participants, within 4 weeks prior to randomization
  • Has a pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
  • Has clinically significant cardiovascular disease within 6 months from first dose of study intervention
  • Has other clinically significant disorders such as: serious active nonhealing wound/ulcer/bone fracture; requirement for hemodialysis or peritoneal dialysis
  • Has preexisting brain or bone metastatic lesions
  • Has received prior systemic therapy for RCC
  • Has received prior radiotherapy for RCC
  • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention; administration of killed vaccines are allowed
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
  • Has a known additional malignancy (other than RCC treated with nephrectomy and/or metastasectomy) that is progressing or has required active treatment within the past 3 years
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs); replacement therapy is allowed
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • Has an active infection, requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection, a known history of Hepatitis B or known active Hepatitis C virus infection
  • Has had an allogenic tissue/solid organ transplant

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A Phase 2 Trial to Evaluate the Safety and Efficacy of NKT2152 in Combination With Palbociclib (Doublet) and With Palbociclib and Sasanlimab (Triplet) in Subjects With Advanced or Metastatic Clear Cell Renal Cell Carcinoma


Condition: ccRCC, Clear Cell Renal Cell Carcinoma, Kidney Cancer, Kidney Neoplasms, Renal Cancer, Renal Neoplasms, Recurrent Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma, Refractory Renal Cell Carcinoma, Advanced Renal Cell Carcinoma, Carcinoma, Neoplasms, Carcinoma, Renal Cell, Neoplasms, Glandular and Epithelial, Neoplasm by Histology, Adenocarcinoma, Urologic Neoplasms, Urogenital Neoplasms, Neoplasms by Site, Kidney Diseases, Urologic Diseases

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05935748

Sponsor: NiKang Therapeutics, Inc.

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Must have locally advanced or metastatic ccRCC and have progressed or relapsed after at least 1 prior anti-VEGF/VEGFR systemic therapy and 1 ICI.
  • Measurable disease per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
  • KPS score of at least 70%
  • Able to swallow oral medications.

Exclusion Criteria:

  • Active CNS metastases and/or carcinomatous meningitis
  • Has had any major cardiovascular event within 6 months or clinically significant cardiovascular disease
  • Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 3 months before administration of study drug.
  • Has known HIV
  • History of hepatitis B or known active hepatitis C infection
  • Has received prior treatment with NKT2152, other HIF2α inhibitors, other CDK 4/6 inhibitors, palbociclib, or sasanlimab
  • Radiation therapy for bone metastasis within 2 weeks, or any other external radiation therapy within 4 weeks before administration of the first dose of study treatment
  • Corrected QT interval calculated by Fridericia formula (QTcF) > 480 ms within 28 days prior to first dose
  • Hypoxia or requires intermittent or chronic supplemental oxygen or any chronic lung condition which has required supplemental oxygen in the past
  • Has a history of interstitial lung disease
  • Has any active or recent history of a known or suspected autoimmune disease

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A Phase II Randomized Trial of Cabozantinib (NSC #761968) With or Without Atezolizumab (NSC #783608) in Patients With Advanced Papillary Renal Cell Carcinoma (PAPMET2)


Condition: Metastatic Papillary Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05411081

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Participants must have a histologically confirmed diagnosis of metastatic papillary renal cell carcinoma (PRCC), either type 1 or type 2. (NOTE: A designation of type 1 or type 2 should be made by the local pathologist if possible but is not required). Mixed histologies which contain type 1 or type 2 along with any other RCC histology/histologies will be allowed provided that they contain a papillary component
  • Participants must have measurable disease per RECIST 1.1 criteria. All measurable lesions must be assessed by CT or magnetic resonance imaging (MRI) within 28 days prior to registration. All non-measurable lesions must be assessed by CT or MRI, or nuclear medicine bone scan within 42 days prior to registration. The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. If there is clinical suspicion for bone metastases at the time of enrollment (at the discretion of the investigator), bone scan must be performed at baseline (within 42 days prior to registration)
  • Participants with new or progressive brain metastases (active brain metastases) must not require immediate central nervous system (CNS) specific treatment at the time of study registration or anticipated during the first cycle of therapy. Patients with leptomeningeal disease are excluded from enrolling
  • Participants with measurable disease, per RECIST version (v)1.1, must be present outside the CNS
  • Participants must have no history of intracranial hemorrhage or spinal cord hemorrhage
  • Participants, if needed, must receive a stable dose of anti-convulsant therapy
  • Participants must complete all prior radiation therapy at least 14 days prior to registration. Participants must have recovered to =< grade 1 from all associated toxicities at the time of registration unless the toxicity is determined to be not clinically significant by the registering investigator
  • Participants must be >= 18 years of age
  • Participants must have a complete physical examination and medical history within 28 days prior to registration
  • Participants must have a Zubrod performance status of 0-2
  • White blood count (WBC) >= 2 x 10^3/uL (within 28 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1.5 x 10^3/uL (within 28 days prior to registration)
  • Platelet count >= 100 x 10^3/uL (within 28 days prior to registration)
  • Lymphocyte count >= 0.5 x 10^3/uL (within 28 days prior to registration)
  • Hemoglobin (>= 9 g/dL) (within 28 days prior to registration). Participants may be transfused to meet this criterion
  • Total serum bilirubin =< 1.5 x the institutional upper limit of normal (ULN) unless history of Gilbert's disease (within 28 days prior to registration). Participants with history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN
  • Aspartate aminotransferase (AST) must be =< 3 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGOT) must be =< 5 x the institutional ULN (within 28 days prior to registration)
  • Alanine aminotransferase (ALT), must be =< 3 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGPT) must be =< 5 x the institutional ULN (within 28 days prior to registration)
  • Participants must have serum creatinine =< 2 x the institutional ULN OR creatinine clearance (either measured or calculated) > 30 mL/min and obtained within 28 days prior to registration
  • Participants must have urine protein < 3+ within 28 days prior to registration. If urine protein is 3+ or greater, then urine protein by 24-hour collection must show less than 3 grams of protein
  • Participants must have documented blood pressure of systolic blood pressure (SBP) < 150 mm Hg or diastolic blood pressure (DBP) < 100 mm Hg within 14 days prior to registration
  • Participants with known human immunodeficiency virus (HIV) must be on effective anti-retroviral therapy at registration and have undetectable viral load within 6 months of registration
  • Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy within 6 months prior to registration, if indicated
  • Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load within 6 months prior to registration
  • Participants must be able to take oral medications (i.e., swallow pills whole). Participants must not have gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures that could in the opinion of the treating investigator affect absorption, or active peptic ulcer disease. Participants with intractable nausea or vomiting are not eligible
  • Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
  • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
  • NOTE: For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
  • As a part of the OPEN registration process for OPEN access instructions) the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Exclusion Criteria:

  • Participants must not have undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment
  • Participants must not have ongoing requirements for corticosteroids as therapy for CNS disease
  • Participants must not have cavitating pulmonary lesions
  • Participants must not have uncontrolled pleural effusions, pericardial effusions, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters (e.g., PleurX) are allowed
  • Participants must not have tumor invading the gastrointestinal (GI) tract or evidence of endotracheal or endobronchial tumor within 28 days prior to registration
  • Participants must not have evidence of tumor invading or encasing any major blood vessels
  • Participants must not have had major surgery within 28 days prior to registration, and participants must have recovered from any adverse effects of surgery
  • Participants must not have had prior treatment with cabozantinib for any reason
  • Participants must not have had prior treatment or adjuvant therapy with PD-1/PD-L1 checkpoint inhibitors for any reason within the past 6 months
  • Participants must not have received more than one prior systemic therapy for advanced or metastatic renal cell carcinoma with the exception of another VEGF inhibitor Food and Drug Administration (FDA)-approved for advanced RCC (i.e., pazopanib, bevacizumab, sorafenib or axitinib). If a participant develops metastatic disease within six months of discontinuation of adjuvant therapy, this will constitute one prior systemic therapy for advanced or metastatic RCC. If a patient develops metastatic disease and more than six months has elapsed since discontinuation of adjuvant therapy, this will not constitute prior systemic therapy for advanced or metastatic RCC
  • Participants must not take within 14 days prior to registration, nor plan to take while on protocol treatment, any strong CYP3A4 inhibitors (e.g. boceprevir, cobicistat, danoprevir, elvitegravir/RIT, fluvoxamine, indinavir, itraconazole, ketoconazole, lopinavir/RIT, nefazodone, nelfinavir, posaconazole, ritonavir, telaprevir, telithromycin, tipranavir/RIT, or voriconazole,); Please refer to https://drug-interactions.medicine.iu.edu/MainTable.aspx for the updated CYP3A4 inhibitors or inducers
  • Participants must not take within 14 days prior to registration, nor plan to take while on protocol treatment, any strong CYP3A4 inducers (e.g. avasimibe, phenytoin, rifampin, rifabutin); Please refer to https://drug-interactions.medicine.iu.edu/MainTable.aspx for the updated CYP3A4 inhibitors or inducers
  • Participants must not be receiving or planning to receive any other investigational agents at time of registration
  • Participants must not have been diagnosed with a clinically significant autoimmune disease, exceptions such as diabetes, eczema, and vitiligo are allowed. Other non-clinically significant autoimmune diseases are allowed if approved by the registering investigator
  • Participants must not be on steroid doses > 10 mg prednisone equivalent. Replacement steroid doses for adrenal insufficiency will be allowed. Also, short duration steroid therapy to prevent allergic reactions are acceptable (e.g. prior to CT imaging)
  • Participants must not have any clinical evidence of congestive heart failure (CHF) (specifically, New York Heart Association [NYHA] class III [moderate] or class IV [severe]) at the time of registration
  • Participants must not have known history of congenital long QT syndrome and must not have experienced unstable angina pectoris, clinically significant cardiac arrhythmias, or stroke (transient ischemic attack [TIA] or other ischemic event) within 90 days prior to registration
  • Participants must not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 90 days of registration, unless clinically stable with ongoing medical management
  • Participants must not have had any clinically-significant GI bleeding within 3 months prior to registration and participants must not have a GI disorder which (at the discretion of the investigator) bears a high risk of perforation or fistula (e.g. Crohn's disease)
  • Participants must not have had hemoptysis of >= (2.5 mL) of red blood, and do not demonstrate any other signs indicative of pulmonary hemorrhage within 3 months prior registration
  • Participants must not be pregnant or nursing, due to VEGF therapy being toxic to embryogenesis. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
  • Participants must not be on warfarin, at therapeutic doses. Low dose aspirin for cardio-protection (per local applicable guidelines) and low molecular weight heparin (LMWH) are allowed

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REPLICA: Real Patient Life Treatment With Cabozantinib in Monotherapy or in Combination With Nivolumab in Patients With Advanced or Metastatic RCC: a Descriptive and Prospective Non Interventional Study.


Condition: Advanced or Metastatic Renal Cell Carcinoma

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT04106349

Sponsor: Ipsen

Phase:

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Males or females aged 18 years and older
  • Patients scheduled to receive Cabometyx® in monotherapy or in combination with nivolumabfor advanced or metastatic renal cell carcinoma
  • Decision to treat patients with Cabometyx® in monotherapy or in combination with nivolumab has to be taken prior to and independent from participation in the clinical study
  • Provision of written informed consent

Exclusion Criteria:

  • Participation in another interventional clinical study at the same time
  • Previous participation in this clinical study

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A Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Advanced Renal Cell Carcinoma With Bone Metastasis (RadiCal)


Condition: Advanced Renal Cell Carcinoma, Chromophobe Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma, Collecting Duct Carcinoma, Kidney Medullary Carcinoma, Metastatic Malignant Neoplasm in the Bone, Papillary Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Unclassified Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04071223

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Documented histologic or cytologic diagnosis of renal cell cancer (RCC). All subtypes of RCC are eligible including but not limited to clear cell, papillary, chromophobe, translocation, collecting duct carcinoma, medullary carcinoma, and unclassified categories. Enrollment of non-clear cell patients will be limited to 20% of the total sample size (~ 42 patients). Once this goal is met, accrual of non-clear cell patients will be discontinued (a notice will be sent out 2 weeks in advance). Sarcomatoid and rhabdoid differentiation are allowed
  • Presence of at least 1 metastatic bone lesion not treated with prior radiation is required.
  • The presence of bone metastases can be detected by computed tomography (CT), magnetic resonance imaging (MRI), Tc-99m bone scan or positron emission tomography (PET) (fludeoxyglucose F-18 [FDG] or sodium fluoride [NaF]) imaging. Patients with non-measurable bone-only disease are allowed. Patients may have received prior radiation therapy for bone metastases or other external radiation >= 7 days prior to registration, as long as they still have at least 1 metastatic bone lesion not treated with radiation. Patients with visceral metastases are allowed, as long as they have at least one untreated bone metastases
  • No prior treatment with cabozantinib
  • No treatment with any type of small molecular kinase inhibitor (including investigational kinase inhibitors) within 2 weeks or 5 half-lives (whichever is shorter) of registration or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 3 weeks of registration
  • No prior hemibody external radiotherapy
  • No prior therapy with radium-223 dichloride or systemic radiotherapy (such as samarium, strontium)
  • No major surgery within 6 weeks of randomization. Procedures such as thoracentesis, paracentesis, percutaneous biopsy, Moh's or other topical skin surgery, Lasik eye surgery are not considered major surgery. Patients who have had a nephrectomy may be registered >= 3 weeks after surgery, providing there are no wound-healing complications. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
  • Recovery to baseline or =< grade 1 CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically nonsignificant and/or stable on supportive therapy
  • The use of osteoclast targeted therapy including either bisphosphonates or denosumab is mandated on this study except in patients with contraindications as determined by the treating investigator, including:
  • Hypocalcemia
  • Hypophosphatemia
  • Renal impairment including those with a glomerular filtration rate (GFR) < 35 mL/min using the Cockcroft-Gault equation or acute renal impairment
  • Hypersensitivity to drug formulation
  • Dental condition or need for dental intervention that per the investigator would increase the risk of osteonecrosis of jaw (ONJ).
  • Use of osteoclast targeted therapy or reason against use needs to be recorded in the electronic case report form (eCRF). Additionally, reason for discontinuation of osteoclast targeted therapy need to be appropriately documented in the eCRF
  • Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
  • Therefore, for women of childbearing potential only, a negative urine pregnancy test done =< 28 days prior to registration is required. A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
  • Karnofsky performance status >= 60%
  • No brain metastases or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
  • No imminent or established spinal cord compression based on clinical symptoms and/or imaging. In patients with untreated imminent or established spinal cord compression, treatment with standard of care as clinically indicated should be completed at least 2 weeks before registration
  • No imminent or impending pathologic fracture based on clinical symptoms and/or imaging. In patients with untreated imminent or impending pathologic fracture, treatment with standard of care as clinically indicated should be completed at least 2 weeks before registration
  • No significant, uncontrolled intercurrent or recent illness, including but not limited to the following conditions:
  • Cardiovascular disorders: Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia; uncontrolled hypertension defined as sustained blood pressure > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment; stroke (including transient ischemic attack), myocardial infarction, or other ischemic event, within 6 months before randomization; thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 1 month before randomization
  • Gastrointestinal disorders: Disorders associated with a high risk of perforation or fistula formation: active inflammatory bowel disease, active diverticulitis, active cholecystitis, active symptomatic cholangitis or active appendicitis, active acute pancreatitis or active acute obstruction of the pancreatic or biliary duct, or active gastric outlet obstruction; abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 3 months before randomization. Note: Complete healing of an intra-abdominal abscess must be confirmed before randomization
  • No clinically significant hematuria, hematemesis, or hemoptysis, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 3 months before randomization
  • No lesions invading major pulmonary blood vessels
  • No other clinically significant disorders:
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (with no medications prohibited by this protocol [e.g. drug-drug interactions]) with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (with no medications prohibited by this protocol [e.g. drug-drug interactions]), if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load (with no medications prohibited by this protocol [e.g. drug-drug interactions])
  • No serious non-healing wound or ulcer
  • No malabsorption syndrome
  • No uncompensated/symptomatic hypothyroidism
  • No moderate to severe hepatic impairment (Child-Pugh B or C)
  • No requirements for hemodialysis or peritoneal dialysis
  • No history of solid organ transplantation
  • No chronic concomitant treatment with strong CYP3A4 inducers or inhibitors. Because the list of these agents is constantly changing, it is important to regularly consult a frequently updated medical reference. Patients may not have received a strong CYP3A4 inducer within 12 days prior to registration nor a strong CYP3A4 inhibitor within 7 days prior to registration
  • No concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants include:
  • Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
  • Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 9 g/dl (transfusions allowed)
  • Calculated (calc.) creatinine clearance >= 30 mL/min using the Cockcroft-Gault equation
  • Total bilirubin =< 1.5 x upper limit of normal (ULN), for patients with Gilberts disease =< 3.0 x ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN
  • Urine protein to creatinine (UPC) ratio =< 2 mg/mg OR 24-hr urine protein < 2 g

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UroCCR Database: French Research Network for Kidney Cancer (National Multidisciplinary Clinical and Biological Database on Kidney Cancer)


Condition: Kidney Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT03293563

Sponsor: University Hospital, Bordeaux

Phase:

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Adult patient with kidney cancer
  • Patient with no opposition to collection of its data for the study

Exclusion Criteria:

  1. none

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TFE Renal Cell Carcinoma: A Prospective Registry and Translational Research Initiative


Condition: Renal Cell Carcinoma

Study Type: Observational [Patient Registry]

Clinical Trials Identifier NCT 8-digits: NCT03630536

Sponsor: Children's Hospital Medical Center, Cincinnati

Phase:

Eligibility:

  • Age: minimum N/A maximum N/A
  • Gender: All

Inclusion Criteria:

  • All patients of any age with a suspected diagnosis or confirmed diagnosis of a TFE Renal Cell Carcinoma.
  • Unless the patient is deceased, all patients and/or one parent or legal guardian must provide written informed consent as well as HIPAA/release of information consent.

Exclusion Criteria:

  • Any patient that has not been diagnosed with TFE Renal Cell Carcinoma

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Evaluation of Urinary Exosomes Presence From Clear Cell Renal Cell Carcinoma


Condition: Clear Cell Renal Cell Carcinoma

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT04053855

Sponsor: Centre Hospitalier Universitaire de Saint Etienne

Phase:

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients:
  • All patients with renal mass requiring surgery (partial or total nephrectomy)
  • Social security affiliation
  • Signed informed consent Control :
  • Patients hospitalized in the urology department without cancer and without known renal mass
  • Unscheduled nephrectomy
  • Social security affiliation
  • Signed informed consent

Exclusion Criteria:

  • Insufficient volume of urine sample (< 100 ml)
  • Patients with a urinary catheter
  • Patients under court-ordered guardianship or curators

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High Dose IL-2 in Combination With Anti-PD-1 to Overcome Anti-PD-1 Resistance in Metastatic Melanoma and Renal Cell Carcinoma


Condition: Melanoma Stage Iv, Renal Cell Carcinoma, Metastatic

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03991130

Sponsor: Gregory Daniels

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patient has the ability to understand and the willingness to sign a written informed consent.
  • Age ≥ 18 years at the time of consent.
  • At least 6 weeks of prior anti-PD-1 therapy with documented clinical or radiographic progression. Last anti-PD-1 therapy must be within 6 months of enrollment.
  • Histologically-confirmed diagnosis of unresectable stage III or metastatic (stage IV) melanoma or renal cell carcinoma
  • Measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1, and obtained by imaging within 28 days prior registration for protocol therapy.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 28 days prior to registration for protocol therapy.
  • Adequate hepatic function within 28 days prior to registration for protocol therapy defined as meeting all of the following criteria:
  • total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN (except in patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl.)
  • and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
  • and alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
  • Adequate renal function within 28 days prior to registration for protocol therapy defined by either of the following criteria:
  • Serum creatinine ≤ 1.5 mg/dL
  • OR if serum creatinine > 1.5 mg/dL, estimated glomerular filtration rate (GFR) ≥ 50 mL/min
  • Adequate hematologic function within 28 days prior to registration for protocol therapy defined as meeting all of the following criteria:
  • hemoglobin ≥ 9.0 g/dL
  • and absolute neutrophil count (ANC) ≥ 1000/L without the support of filgrastim
  • white blood cells (WBC) ≥ 3000/L
  • and platelet count ≥ 100 × 109/L
  • Adequate coagulation functioning within 28 days prior to registration for protocol therapy defined by either of the following criteria:
  • INR < 1.5 × ULN
  • OR for subjects receiving warfarin or LMWH, the subjects must, in the investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy.
  • Adequate pulmonary and cardiac function for HD IL-2 (will be assessed clinically)
  • Female subjects of childbearing potential must have confirmed negative urine or serum pregnancy test prior to drug administration and be willing to use two methods of birth control.
  • Male subjects who are not surgically sterile (vasectomy) must agree to use an adequate method of contraception.
  • Subject's toxicities from prior treatments must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo)

Exclusion Criteria:

  • Active infection requiring systemic therapy
  • Women who are pregnant or breastfeeding.
  • Second active malignancy within the past 5 years with the exception of localized basal or squamous cell skin cancer, in situ cervical or bladder cancer, or localized prostate cancer under active surveillance.
  • Active symptomatic central nervous system (CNS) metastases. Prior treated metastases or asymptomatic metastases are allowed. Patient can receive radiation between treatments if deemed medically necessary.
  • Surgery within 4 weeks prior to study treatment except for minor procedures.
  • Uncontrolled or poorly-controlled hypertension (> 160 mmHg systolic or > 100 mmHg diastolic for > 4 weeks) despite standard medical management.
  • Serious or non-healing wounds, ulcers, or bone fractures within 28 days prior to initiation of study treatment.
  • Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to initiation of study treatment.
  • Has any condition that, in the opinion of the investigator, might jeopardize the safety of the patient or interfere with protocol compliance.
  • Has any mental or medical condition that prevents the patient from giving informed consent or participating in the trial.
  • Known hypersensitivity to nivolumab or IL-2 or any of their components.
  • Known history of active tuberculosis.
  • Concurrent systemic steroid therapy with doses above physiologic level (more than 10 mg of prednisone daily).
  • Active autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis requiring treatment. Patients cannot be on immunosuppressive medications other than physiologic replacement doses of prednisone (less than 10 mg per day at enrollment) or equivalent steroid. Asymptomatic patients or those stable on non-immunosuppressive medications are eligible.
  • Treatment with any investigational agent within 21 days prior to initiation of study treatment and the subject must have recovered from the acute toxic effects of the regimen with the exception of prior anti-PD-1.

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AURORAX-0087A: Glycosaminoglycan Scores for Surveillance of Recurrence in Leibovich Points ≥5 Non-metastatic Clear Cell Renal Cell Carcinoma


Condition: Clear Cell Renal Cell Carcinoma

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT04006405

Sponsor: Elypta

Phase:

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Pre-screening inclusion criteria
  • Size of primary tumor >4cm (>cT1a) in greatest dimension on pre-operative abdominal CT-scan
  • Size of primary tumor ≤4cm is allowed if pre-operative abdominal CT-scan shows suspected RCCs with radiological sign of venous tumor thrombus (renal vein or caval).
  • Pre-operative CT-scan of chest and abdomen show no signs of metastatic disease
  • Localized and biopsy proven clear cell RCC (ccRCC) under active surveillance which at timepoint of study recruitment, opted for surgery because of growth rate of primary tumor to a size > 4cm
  • Elected for curative intent surgery for RCC Final screening inclusion criteria
  • Any gender being 18 years or older at timepoint of final inclusion
  • In postoperative pathology report shown to be ccRCC subtype according to 8th Edition of the American Joint Committee on Cancer (AJCC)
  • Leibovich points (LP) ≥5 according to Leibovich score system (2003)
  • If pathology report shows multiple subtypes in same tumor, as long as the majority of tumor is ccRCC (>50%), participant can be included Exclusion Criteria: Pre-screening exclusion criteria
  • TNM-stage T(any) N(any) M1 according to AJCC, i.e. metastatic disease at diagnosis
  • Absence of preoperative chest imaging (chest CT) within 60 days prior to primary surgery
  • Previous history of curatively treated for other cancers, still not deemed fully cured and participant still under surveillance for said cancer
  • Participants offered active surveillance for RCC instead of curative intent surgery
  • Participants offered any type of thermal ablation treatment instead of surgery, i.e. LP cannot be assessed Final screening

Exclusion Criteria:

  • Pre-screening exclusion criteria
  • TNM-stage T(any) N(any) M1 according to AJCC, i.e. metastatic disease at diagnosis
  • Absence of preoperative chest imaging (chest CT) within 60 days prior to primary surgery
  • Previous history of curatively treated for other cancers, still not deemed fully cured and participant still under surveillance for said cancer
  • Participants offered active surveillance for RCC instead of curative intent surgery
  • Participants offered any type of thermal ablation treatment instead of surgery, i.e. LP cannot be assessed Final screening exclusion criteria
  • Participants with AJCC cN0 status at preoperative imaging in whom a clinically suspicious regional lymph-node metastases (enlarged lymph node(s)) is noted during primary surgery, but who subsequently do not undergo any lymph node dissection. (Note: participants with cN0 status at pre-operative imaging and no clinical signs of regional lymph node metastases during primary surgery can still be included irrespective of lymph node dissection having been performed, i.e. being pN0 or pN1 if it is performed or pNx if it is not performed)
  • Participants with AJCC cN1 status at pre-operative imaging in which lymph node dissection is not performed (i.e. pNx).
  • Elected for any adjuvant therapy (i.e. systemic therapy) outside or within any clinical study
  • Non-clear cell RCC histology or benign tumor (i.e. oncocytoma and angiomyolipoma, which are the most common benign types, but also any other rare types of benign renal tumors) after pathological analysis
  • Any hereditary form of RCC (e.g. Von Hippel-Lindau, Birt-Hogg-Dubé, Hereditary Papillary RCC)
  • RCC with pure sarcomatoid differentiation, also called sarcoma of the kidney
  • Previous history of curatively treated for RCC with a suspected de novo RCC in the remaining kidney tissue
  • Prior or current use of instillation therapy with hyaluronic acid and/or chondroitin sulfate (HA-CS).
  • Use of heparin, including low molecular weight heparin (e.g. Enoxaparin, Dalteparin, Tinzaparin) for concurrent disease in need of blood dilution (e.g. ongoing deep vein thrombosis or lung emboli). Note: use of of heparin for thrombus prophylaxis in conjunction with primary surgery or postoperatively ≤4 weeks will be allowed.
  • Patients who were not radically operated during primary surgery with the exception of histological positive surgical margin in participants who have undergone partial nephrectomy.

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Phase II Study of Olaparib in Metastatic Renal Cell Carcinoma Patients Harboring a BAP-1 or Other DNA Repair Gene Mutations (ORCHID)


Condition: Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma, Kidney Cancer, Renal Carcinoma, Kidney Cancer Metastatic

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03786796

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum 120 Years
  • Gender: All

Inclusion Criteria:

  • Willing and able to provide written informed consent. Provision of informed consent is required prior to any study procedures.
  • Patients aged 18 years of age or older.
  • Histological proof of renal cell carcinoma (both clear cell and non-clear cell allowed).
  • Metastatic (AJCC Stage IV) renal cell carcinoma.
  • Somatic or germline mutation in BAP-1, ATM, BRCA1, BRCA2, PALB2, CHEK2, BRIP1, RAD51C, BARD1, CDK12, CHEK1, FANCL, PP2R2A, RAD51B, RAD51D, or RAD54L as documented by a clinical CLIA-grade, tissue, saliva or blood-based genetic test.
  • At least one prior treatment with an anti-angiogenic agent or immune checkpoint inhibitor.
  • Any number of prior systemic therapies is allowed (cytokine, anti-angiogenic, mTOR, immune checkpoint blockage or clinical trial).
  • Must have measurable disease as defined by RECIST 1.1 criteria.
  • Participants must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
  • Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional ULN unless liver metastases are present in which case they must be ≤ 5 x ULN. Note: Patients with elevations in bilirubin, AST, or ALT should be thoroughly evaluated for the etiology of this abnormality prior to entry and patients with evidence of viral infection should be excluded.
  • Patients must have a creatinine clearance ≥ 40 mL/min calculated by Cockroft-Gault formula or 24 hour urine test.
  • ECOG PS ≤ 1.
  • Participants must have a life expectancy ≥ 16 weeks.
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments.
  • Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50 years old.
  • Radiation-induced oophorectomy with last menses > 1 year ago.
  • Chemotherapy-induced menopause with > 1 year interval since last menses.
  • Surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Male patients must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential.

Exclusion Criteria:

  • Other malignancy unless curatively treated with no evidence of disease for ≥ 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma. Patients with a history of localized triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy > 3 years prior to registration, and that the patient remains free of recurrent or metastatic disease.
  • Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
  • Breast feeding women.
  • Use of any prohibited concomitant medications within the prior 2 weeks.
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  • Participation in another clinical study with an investigational product during the last 2 weeks.
  • Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment.
  • Any previous treatment with PARP inhibitor, including olaparib.
  • Resting ECG with QTc > 500 ms and/or indication of uncontrolled cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, electrolyte disturbances, etc.), or patients with congenital and/or family history of long QT syndrome.
  • Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks. During the study, if co-administration of a strong or moderate inhibitor is required because there is no suitable alternative medication, exception to this criterion may be allowed with a suitable dose reduction of olaparib.
  • Concomitant use of known strong CYP3A inducers (e.g. phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for phenobarbital or enzalutamide and 3 weeks for other agents.
  • Persistent toxicities (> Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
  • Patients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
  • Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
  • Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
  • Unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
  • Known hypersensitivity to olaparib or any of the excipients of the product.
  • Known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.
  • No packed red blood cells and/or platelet transfusions within the last 28 days prior to study entry.

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