Bladder Cancer

Condition: Epithelial Ovarian Cancer, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Urothelial Carcinoma, Non-Small Cell Lung Cancer, Small-Cell Lung Cancer, Endometrial Carcinoma, Head and Neck Squamous Cell Carcinoma, Breast Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04152499

Sponsor: Klus Pharma Inc.

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

• Patients must meet the following criteria for inclusion into the study: Phase I: 1. Patients must be able to provide documented voluntary informed consent. 2. Male or female patient aged 18-75 years. 3. Histologically documented, incurable, locally advanced or metastatic epithelial origin malignant cancer, priority to include but not limited to the following tumor types: Breast cancer Ovarian epithelial cancer Non-small cell lung cancer Gastric adenocarcinoma Small cell lung cancer Urothelial carcinoma Note: Confirmation of TROP2 expression by immunohistology or other means is not required, but the Sponsor will request tissue specimens from fresh or archived materials for determination of TROP2 expression. 4. Measurable disease by CT/MRI during dose escalation. 5. Patients should have an unresectable locally advanced or metastatic solid tumor that is refractory to standard therapies, or have no standard therapies, or standard treatment is not applicable at this stage. 6. Granulocyte count ≥ 1.5×109/L, platelet count ≥ 100×109/L, and hemoglobin ≥ 9 g/dL. 7. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5×ULN. 8. Serum bilirubin ≤ 1.5 mg/dL (Patients with known Gilbert disease who have serum bilirubin level ≤ 3 ×ULN may be enrolled)., aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN), with the exception of patients with hepatic metastases (ALT and AST ≤ 5 × ULN) and patients with hepatic and/or bone metastases (alkaline phosphatase ≤ 5 × ULN). 9. Creatinine clearance ≥ 50 mL/min calculated by Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration, or Modification of Diet in Renal Disease formulas. Note that 24 hour urine collection is not required but is allowed. 10. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. 11. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception during study treatment. Female and male patient treated with SKB264 should continue contraception use for 7 months after the last dose. Such methods include combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion or vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence.
• Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drug. The same rules are valid for male patients involved in this clinical trial if they have a partner of childbirth potential. Male patients must always use a condom.
• Women are excluded from birth control if they had had tubal ligation or a hysterectomy. 12. Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo. 13. Expected survival ≥ 3 months. Phase II: 1. Patients must be able to provide documented voluntary informed consent. 2. Male or female patient aged ≥ 18 years. 3. Histologically or cytologically documented, incurable, locally advanced, recurrent or metastatic cancer, including the following tumor types:
• Cohort 1: triple negative breast cancer (< 1% expression for estrogen receptor [ER] and progesterone receptor [PR] and HER2 negative)
• Cohort 2: ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
• Cohort 3: non-small cell lung cancer
• Cohort 4: gastric adenocarcinoma or gastroesophageal junction adenocarcinoma (HER2 negative)
• Cohort 6: HR+/ HER2- breast cancer (≥1% expression for ER and/or PR and HER2 negative)
• Cohort 7: Head and neck squamous cell carcinoma (including primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx. Other primary tumor sites of HNSCC are not eligible)
• Cohort 8: Endometrial carcinoma (including carcinosarcoma, but excluding sarcoma and neuroendocrine endometrial carcinoma)
• Cohort 9: Urothelial carcinoma (including urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, patients with mixed histology are eligible provided urothelial component > 50% and plasmacytoid component<10%, patients whose tumors contain any neuroendocrine component are not eligible)
• Cohort 10: Cervical cancer (including squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix) Note: Evaluation of TROP-2 expression is required. 4. Measurable disease by CT/MRI. 5. Patients should have an unresectable locally advanced or metastatic solid tumor that is refractory to standard therapies. 6. Neutrophil count ≥ 1.5×109/L, platelet count ≥ 100×109/L, and hemoglobin ≥ 9 g/dL. 7. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5×ULN. 8. Serum bilirubin ≤ 1.5 ×ULN (Patients with known Gilbert disease who have serum bilirubin level ≤ 3 ×ULN may be enrolled), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN), with the exception of patients with hepatic metastases (ALT and AST ≤ 5 × ULN) and patients with hepatic and/or bone metastases (alkaline phosphatase ≤ 5 × ULN). 9. Creatinine clearance ≥ 30 mL/min calculated by Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or Modification of Diet in Renal Disease (MDRD) formulas. Note that 24 hour urine collection is not required but is allowed. 10. ECOG Performance Status 0 or 1. 11. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception during study treatment. Female and male patient treated with SKB264 should continue contraception use for 6 months after the last dose. Such methods include combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion or vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence.
• Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drug. The same rules are valid for male patients involved in this clinical trial if they have a partner of childbirth potential. Male patients must always use a condom.
• Women are excluded from birth control if they had had tubal ligation or a hysterectomy. 12. Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo. Note: Subjects with endocrine AE of any grade are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic. 13. Expected survival ≥ 3 months.

Exclusion Criteria:

1. Patients that meet the following criteria will be excluded from entry into the study: Phase I:
2. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
3. Symptomatic brain metastases or any radiation or surgery for brain metastases within 1 months of first infusion of study drug.
4. Subjects with second primary cancers (except for cured in situ non-melanoma skin cancer and in situ cervical cancer with no relapse in the last 3 years).
5. Require supplemental oxygen for daily activities.
6. Documented Grade ≥ 2 peripheral neuropathy.
7. History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, corneal disease that prevents/delays corneal healing, macular degeneration.
8. Subjects previously treated with TROP 2 targeted therapies.
9. Any standard cancer therapy (e.g. chemotherapy, hormonal therapy, radiotherapy, immunotherapy, biologic therapy treatment, or therapy with traditional Chinese medicines approved for anti-tumor treatment, etc.) within 4 weeks or five half-lives, whichever is shorter, of first infusion of study drug.
10. Any experimental therapy within 4 weeks or five half-lives, whichever is shorter, of first infusion of study drug.
11. Any major surgical procedure within 4 weeks of first infusion of study drug.
12. Diagnosed active liver disease, including viral or other hepatitis, current or history of alcoholism, or cirrhosis.
13. Have known prior positive test results or medical history for human immunodeficiency virus.
14. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg) or diabetes (HbA1c ≥ 9.0%).
15. Subjects who require use of strong inhibitors or inducers of CYP3A4 at least 14 days prior to and throughout Study. Use of strong inhibitors or inducers of CYP3A4 is not allowed in this study. List of representative examples of strong inhibitors or inducers of CYP3A4 is provided in Appendix III.
16. Pregnancy or lactation.
17. Left ventricular ejection fraction < 45% determined by echocardiogram or multiple gated acquisition scan.
18. Resting QTc > 480 msec at baseline.
19. Ascites requiring paracentesis ≥1 per week.
20. Symptomatic pleural effusion (< 90% oxygen saturation).
21. Subjects with non-infectious interstitial lung diseases (ILD) or medical history of pneumonia requiring steroid treatments; severe pulmonary dysfunction caused by lung diseases.
22. New diagnosed thromboembolic events that requires therapeutic intervention over the last 6 months (patients with stable control of lower limb deep venous thrombosis are allowed).
23. The investigator considers other situations that patients are not appropriate to participate in this trial. Phase II:
24. Any patient who was treated in the Phase I part of this study.
25. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
26. Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or other active CNS metastases.
27. Patients with active second primary cancers (except for cured in situ non-melanoma skin cancer and in situ cervical cancer with no relapse in the last 3 years, or other malignant cancers that have been cured and no evidence of recurrence).
28. Require supplemental oxygen for daily activities.
29. Documented Grade ≥ 2 peripheral neuropathy.
30. History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, corneal disease that prevents/delays corneal healing, macular degeneration.
31. Patients previously treated with TROP 2 targeted therapies at any time for early stage or metastatic disease.
32. Any standard cancer therapy (e.g. chemotherapy, hormonal therapy, radiotherapy, immunotherapy, biologic therapy treatment, or therapy with traditional Chinese medicines approved for anti-tumor treatment, etc.) within 4 weeks or 5 half-lives, whichever is shorter, of first infusion of study drug.
33. Any experimental therapy within 4 weeks or 5 half-lives, whichever is shorter, of first infusion of study drug.
34. Any major surgical procedure within 4 weeks of first infusion of study drug.
35. Diagnosed active liver disease, including viral or other hepatitis, current or history of alcoholism, or cirrhosis.
36. Have known prior positive test results or medical history for human immunodeficiency virus.
37. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg) or diabetes (HbA1c ≥ 9.0%).
38. Subjects who require use of strong inhibitors or inducers of CYP3A4 at least 14 days prior to and throughout Study. Use of strong inhibitors or inducers of CYP3A4 is not allowed in this Study. List of representative examples of strong inhibitors or inducers of CYP3A4 is provided in Appendix III.
39. Pregnancy or lactation.
40. Left ventricular ejection fraction < 45% determined by echocardiogram or multiple gated acquisition scan.
41. Resting QTcF > 480 msec at baseline.
42. Ascites requiring paracentesis >1 per week.
43. Symptomatic pleural effusion (< 90% oxygen saturation).
44. History of interstitial lung diseases (ILD) or non-infectious pneumonitis requiring steroid treatments; severe pulmonary dysfunction caused by lung diseases.
45. New diagnosed thromboembolic events that requires therapeutic intervention over the last 6 months (patients with stable control of lower limb deep venous thrombosis are allowed).
46. Known allergic to any components of SKB264, including excipients (including polysorbate-20); or history of severe hypersensitivity to another biologic therapy.
47. The investigator considers other situations that patients are not appropriate to participate in this trial.

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Condition: Solid Tumor

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04794699

Sponsor: IDEAYA Biosciences

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

• Participant must be at least 18 years of age
• Advanced or metastatic solid tumor that has progressed on at least one prior line of treatment or is intolerant to additional effective standard therapy
• Have evidence of homozygous loss of MTAP or MTAP deletion
• Willing to undergo paired fresh biopsy (pre- and post-treatment) procedure. Exceptions may be made for feasibility and safety concerns
• Measurable disease
• ECOG performance status <= 1
• Adequate organ function
• Able to swallow and retain orally administered study treatment
• Recovery from acute effects of prior therapy
• Able to comply with contraceptive/barrier requirements

Exclusion Criteria:

• Known symptomatic brain metastases
• Known primary CNS malignancy
• Current active liver or biliary disease
• Impairment of gastrointestinal (GI) function
• Active uncontrolled infection
• Clinically significant cardiac abnormalities
• Previous treatment with a MAT2A inhibitor and / or PRMT inhibitor or sacituzumab govitecan
• Systemic anti-cancer therapy or major surgery within 4 weeks prior to study entry
• Radiation therapy within 2 weeks prior to study entry
• Prior irradiation to >25% of the bone marrow
• Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inhibitors or inducers
• Currently receiving another investigational study drug.
• Known or suspected hypersensitivity to IDE397/excipients or components

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Condition: Endometrial Cancer, Gastric Cancer, Metastatic Castration-resistant Prostate Cancer, Ovarian Cancer, Colorectal Cancer, Urothelial Cancer, Biliary Tract Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05489211

Sponsor: AstraZeneca

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum 130 Years
• Gender: All

Key Inclusion Criteria:

• Male and female, ≥ 18 years
• Documented advanced or metastatic malignancy
• Eastern Cooperative Oncology Group performance status of 0 or 1 with no deterioration over the 2 weeks prior to baseline or day of first dosing
• All participants must provide a tumour sample for tissue-based analysis
• At least 1 measurable lesion not previously irradiated, except Substudy 3 (Prostate Cancer) which allows participants with non measurable bone metastatic disease
• Adequate bone marrow reserve and organ function
• Minimum life expectancy of 12 weeks
• At the time of screening, contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• All women of childbearing potential must have a negative serum pregnancy test documented during screening
• Female participants must be 1 year post-menopausal, surgically sterile, or using 1 highly effective form of birth control. Female participants must not donate, or retrieve for their own use, ova at any time during this study
• Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile, avoid intercourse, or use a highly effective method of contraception. Male participants must not freeze or donate sperm at any time during this study.
• Capable of giving signed informed consent
• Provision of signed and dated written optional genetic research informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative

Key Exclusion Criteria:

• Any evidence of diseases which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol
• History of another primary malignancy except for adequately resected basal cell carcinoma or in situ squamous cell carcinoma of the skin, or other solid malignancy treated with curative intent
• Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved
• Irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator, for example hearing loss
• Spinal cord compression or brain metastases unless treated
• Leptomeningeal carcinomatosis
• Clinically significant corneal disease
• Active hepatitis or uncontrolled hepatitis B or C virus infection
• Uncontrolled infection requiring IV antibiotics, antivirals or antifungals, for example prodromal symptoms
• Known HIV infection that is not well controlled
• Known active tuberculosis infection
• Mean resting corrected QTcF > 470 ms
• In the judgement of the investigator, history of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause TdP
• In the judgement of the investigator, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives
• Uncontrolled or significant cardiac diseases
• History of non-infectious Interstitial lung disease (ILD)/pneumonitis that required steroids
• Has severe pulmonary function compromise
• Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout period
• Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention
• Prior exposure to anticancer therapies without an adequate treatment washout period prior to enrolment or any concurrent anticancer treatment
• Palliative radiotherapy with a limited field of radiation within ≤ 2 weeks or to more than 30% of the bone marrow within ≤ 4 weeks before the first dose of study intervention
• Major surgical procedure or significant traumatic injury within ≤ 3 weeks of the first dose of study intervention or an anticipated need for major surgery during the study
• Prior treatment with TROP2-directed therapies or other antibody-drug conjugate (ADCs) with deruxtecan payload
• Herbal or natural products intended as treatment or prophylaxis for any type of cancer that may interfere with the activity of the study intervention
• Previous treatment in the present study
• Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks prior to first dose of study intervention or concurrent enrolment in another clinical study
• Severe hypersensitivity to Dato-DXd or any of the excipients, including but not limited to polysorbate 80 or other monoclonal antibodies
• Involvement in the planning and/or conduct of the study
• Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements
• Females that are pregnant, breastfeeding, or planning to become pregnant
• Female participants should refrain from breastfeeding from enrolment throughout the study and for at least 7 months after last dose of Dato-DXd

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Condition: Muscle Invasive Bladder Carcinoma, Stage II Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05581589

Sponsor: University of Washington

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Participants must be at least 18 years of age on the day of signing informed consent. Participant (or legally acceptable representative if applicable) provides written informed consent for trial
• Participants must have either histologically or by clinical consensus (based on imaging and/or exam under anesthesia) confirmed diagnosis of muscle invasive bladder cancer (cT2-T4aN0-N1M0 or cT1-4aN1M0 clinical stage per American Joint Commission on Cancer [AJCC]). Patients with clinical node-positive (N1) stage are eligible provided the lymph node (LN) is confined to the true pelvis and is within the planned surgical LN dissection template; cN1 is defined as a lymph node with >= 15 mm short axis or biopsy-positive for carcinoma
• Must have clinical non-metastatic bladder cancer (M0) determined by cross-sectional Computed tomography (CT) chest, abdomen and pelvis (CAP) or magnetic resonance imaging (MRI)
• Review of pathology by local expert genitourinary (GU) pathologist is required. Any component (%) of non-conventional urothelial (variant histology) noted on transurethral resection of bladder tumour (TURBT) is allowed, for histologic types not listed below. However, for the variant histologic types listed below, the following parameters need to be met:
• Squamous cell carcinoma / squamous cell features need to be pure or predominant (>= 1 variant histologic with total non-conventional urothelial component > 50%).
• Adenocarcinoma / glandular features need to be pure or predominant (>= 1 variant histologic total non-conventional urothelial component > 50%).
• Any % of neuroendocrine / small cell histology is excluded.
• Patients must be considered unfit for cisplatin based on the Galsky et al. criteria or refuse cisplatin despite adequate counseling in cisplatin-fit patients. Especially, for tumors containing squamous cell or glandular features, every effort should be made to discuss the benefit of neoadjuvant cisplatin-based chemotherapy shown in the S8710 trial
• Participants must be deemed eligible for radical cystectomy (RC) and pelvic lymph node dissection (PLND) by both urologist and medical oncologist
• TURBT that showed muscularis propria (or lamina propria for cT1N1 tumors) invasion should be within 12 weeks prior to beginning study therapy. Patients must have available tumor tissue from either initial or repeat TURBT, prior to starting study therapy. Archival and/or fresh tumor tissue sample of a tumor lesion (TURBT specimen) should be provided and must contain muscle invasive component, at least >= T2 tumor (for cT2 tumors), unless clinical stage is cT1N1M0 (in that case muscle invasive component is not necessary). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory, preferably within 14 days from the date slides are cut if possible. Patient must be willing to provide tumor tissue for research. Research samples will not be used for unrelated studies
• A male participant must agree to use a contraception during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. Patients with ECOG PS 2 may be permitted only after discussion with the trial primary investigator (PI) (Dr. Grivas). Evaluation of ECOG PS is to be performed within 7 days prior to the date of enrollment.
• Absolute neutrophil count (ANC) >= 1500/uL (within 10 days prior to the start of study treatment)
• Platelets >= 100 000/uL (within 10 days prior to the start of study treatment)
• Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (within 10 days prior to the start of study treatment) * Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks prior to study drug treatment
• Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 30 ml/min (glomular filtration rate [GFR] can be used in place of creatinine clearance; 24-hour urine collection can be used for more accurate estimate as needed) (within 10 days prior to the start of study treatment) * Creatinine clearance (CrCl) should be calculated per institutional standard
• Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN (within 10 days prior to the start of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =< 2.5 x ULN (within 10 days prior to the start of study treatment)
• International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy (within 10 days prior to the start of study treatment)
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy (within 10 days prior to the start of study treatment)
• Patients must agree to undergo curative intent surgery.

Exclusion Criteria:

• Patients with any % of neuroendocrine / small cell histology
• Patients considered to be medically unfit for SG, TURBT or radical cystectomy (per investigator discretion)
• Prior systemic anti-cancer therapy, including investigational agent/device within 4 weeks or prior radiation therapy within 2 weeks. Intravesical therapies are allowed without specified treatment interval
• Known locally advanced (unresectable, e.g. cT4b) or metastatic (cN2-3, M1) cancer on baseline radiographic imaging (CT or MRI) obtained within 28 days prior to registration
• Active infection requiring systemic antibiotic therapy at the time of trial initiation. Human immunodeficiency virus (HIV)-positive patients on active therapy are eligible as long as their viral load is undetectable and CD4 count is within normal parameters during the time of trial therapy initiation
• Known history of active hepatitis B (defined as hepatitis B surface antigen [HBsAg] detected or positive hepatitis B virus [HBV] polymerase chain reaction [PCR] test) or known active hepatitis C virus (defined as HCV ribonucleic acid (RNA) [qualitative] detected) infection. Note: no testing for hepatitis B and hepatitis C is required if there is no clinical suspicion of such infection
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Known personality, psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
• Patients may not have concurrent upper urinary tract (i.e., ureter, renal pelvis) invasive urothelial carcinoma. Patients with history of non-invasive (Ta, Tis) upper tract urothelial carcinoma that have been definitively treated with at least one post-treatment disease assessment (i.e., cytology, biopsy, imaging) that demonstrates no evidence of residual disease are eligible. Previously treated or concurrent non-invasive (Ta, Tis) urethra carcinoma is allowed, but history of or concurrent invasive urethra carcinoma is excluded
• Patients may not have another malignancy that could interfere with the evaluation of safety or efficacy of of SG. Patients with prior malignancy will be allowed without PI approval in the following circumstances:
• Not currently active and completed therapy at least 2 years prior to the date of registration.
• Non-invasive cancer, such as low risk cervical cancer or any carcinoma in situ.
• Localized (early stage) cancer treated with curative intent (without evidence of recurrence and intent for further therapy), and in which no systemic chemotherapy was indicated (e.g., low/intermediate risk prostate cancer, non-melanoma skin cancer, etc.). Low/intermediate risk prostate cancer on active surveillance or watchful waiting is allowed. Other cancers not meeting these criteria must be discussed with trial PI (Dr. Grivas)
• Patients may not have undergone major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury =< 3 weeks prior to starting SG, or who have not recovered from side effects of such procedure or injury
• Have active (based on symptoms, endoscopic or biopsy findings) chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) at time of trial therapy initiation or history of GI perforation within 6 months of enrollment
• Patients may not have clinically significant cardiac diseases, including any of the following:
• History or presence of serious uncontrolled ventricular arrhythmias.
• Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), New York Heart Association (NYHA) Class III or greater congestive heart failure (CHF) or left ventricular ejection fraction of < 40%, cerebrovascular accident (CVA), transient ischemic attack (TIA).
• Patients unwilling or unable to comply with the protocol or with known allergy to SG, its analogues, or excipients in the various formulations
• Patients may not participate in any other therapeutic clinical trials, including those with other investigational agents not included in this trial before radical cystectomy
• WOCBP with positive urine pregnancy test within 72 hours prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required for eligibility. Active lactation is exclusion
• History of allogeneic solid visceral organ transplant, Gilbert's disease, prior systemic irinotecan or topotecan or other topoisomerase-1 inhibitor, or concomitant medications that significantly interfere with ABCA1 transporter or UGT1A1 with no alternate option available

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Condition: Advanced Solid Tumors

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05941507

Sponsor: LigaChem Biosciences, Inc.

Phase: Phase 1/Phase 2

Eligibility:

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

Key Inclusion Criteria:

• Phase 1 Dose Escalation: histologically or cytologically confirmed advanced solid tumors refractory to standard of care treatment.
• Phase 2 Dose Expansion*: select histologically or cytologically confirmed advanced solid tumors refractory to standard of care treatment. *expansion cohort indications to be prioritized based on data from Phase 1 dose escalation.
• Prior treatment with TROP2-directed therapy is permitted.
• Measurable disease as defined by RECIST v1.1 or RANO-BM.
• Willingness to provide archival tumor tissue when available or to undergo pre-treatment biopsy if not available.
• Mandatory pre- and on-treatment biopsies for enrichment cohorts in Phase 1 dose escalation and Phase 2 expansion cohorts if deemed medically feasible and safe.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function as defined by:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L (1500/µL), without colony-stimulating factor support for the past 14 days
• Platelets ≥100.0 x 109/L (100 000/µL)
• Hemoglobin ≥9.0 g/dL
• Aspartate aminotransferase (AST) ≤2.5 x ULN; alanine aminotransferase (ALT) ≤2.5 x ULN (AST, ALT ≤5 x ULN if liver metastases present)

Key Exclusion Criteria:

• Active or progressing central nervous system (CNS) metastases or any evidence of leptomeningeal disease. Note: Patients with stable or treated CNS metastases may be eligible if all of the following criteria are met: 1) localized treatment for brain metastases completed at least 4 weeks prior to the first dose of study drug 2) no new or progressive neurologic symptoms and without need for immediate local therapy, steroids or anticonvulsants for symptom control (stable or decreasing steroid dose (a stable dose of ≤4 mg dexamethasone oral or equivalent) is permitted) 3) stable brain metastases for at least 1 month prior to screening (baseline) brain MRI.
• Persistent toxicities from previous systemic antineoplastic treatments >Grade 1, excluding alopecia and vitiligo.
• Systemic antineoplastic therapy (including antiestrogen therapy) within 5 half-lives or 4 weeks, whichever is shorter, prior to first dose of the study drug.
• Concomitant use of systemic steroids at dose of >10 mg of prednisone or its equivalent per day (exception for brain metastases, as described in exclusion criteria #1 above).

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Condition: Localized Muscle Invasive Bladder Urothelial Carcinoma, Muscle-Invasive Bladder Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05833867

Sponsor: Omar Mian

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

• Participants must have histologically or cytologically confirmed muscle-invasive bladder cancer (MIBC) (T2-T4aN0M0). Participants with mixed urothelial carcinoma will be eligible for the trial, except for small cell or neuroendocrine component
• Participants must have received no prior systemic chemotherapy for this disease. Participants must refuse conventional radio-sensitizing chemotherapy, (and/or) must not be eligible for or refuse cystectomy while on study Participants may receive cystectomy following the end of treatment (EOT)/ Safety Visit if deemed necessary by their clinical team while still in follow-up.
• Performance status: ECOG Performance status ≤ 2
• Participants must have normal organ and marrow function as defined below:
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x laboratory upper limit of normal (ULN)
• Total serum bilirubin ≤ 2.0 x ULN
• Absolute neutrophil count (ANC) ≥ 1500/μL
• Platelets ≥ 100,000/μL
• Hemoglobin ≥ 9.0 g/dL
• Serum calcium ≤ 12.0 mg/dL
• Calculated Creatinine Clearance ≥ 30 mL/min. Calculated using Cockcroft-Gault formula: Creatinine Clearance = [[140
• age(yr)] multiplied by body weight(kg)]/ [72 multiplied by serum Cr(mg/dL)] (multiply total by 0.85 for women).
• Participants must have adequate baseline bladder function to warrant bladder preservation as assessed by the treating provider, including absence of bilateral hydronephrosis or acute obstruction related to bladder tumor after TURBT. Unilateral hydronephrosis is permitted.
• Participants must undergo a TURBT within ≤ 60 days prior to treatment start. In a situation where a participant is referred from an outside site to the Cleveland Clinic Foundation, participant must have a repeat cystoscopy by the urologist who will be following the participant on the clinical trial to assess the adequacy of the prior TURBT. Participant may then undergo repeat TURBT if deemed necessary as standard of care by the treating urologist.
• Participants may have either completely or partially resected tumors as long as the treating urologist attempted maximal resection.
• Participant must undergo radiological staging within 60 days prior to treatment start. Imaging of chest, abdomen, and pelvis must be performed using CT or MRI. Participants must not have evidence of T4b and/or N1-3 dT4bN1-3 disease. Eligibility is based on review by Cleveland Clinic Foundation (CCF) radiology department and/or PI.
• Participants must not have had urothelial carcinoma or any histological variant at any site outside of the urinary bladder within the previous 24 months except Ta/T1/Carcinoma in situ (CIS) of the upper urinary tract including renal, pelvis, and ureter if the participant had undergone complete nephroureterectomy.
• Participants must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Participants receiving or utilizing any other investigational agents or devices.
• Has received prior pelvic / local radiation therapy for MIBC or any other cancer type.
• Has received any prior systemic treatment, chemoradiation, and / or radiation therapy for MIBC or non-muscle-invasive bladder cancer (NMIBC). Note: Prior treatment for NMIBC with intravesical instillation therapy such as BCG or intravesical chemotherapy is permitted.
• Has diagnosed Bilateral hydronephrosis.
• Has limited bladder function as noted by a provider, with frequency of small amounts of urine, urinary incontinence including stress/urge, requires self-catheterization or a permanent indwelling catheter.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to SG or any of its' components.
• Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding women are excluded from this study because SG and radiation effects during pregnancy have potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with SG, breastfeeding should be discontinued if the mother is treated with Sacituzumab Govitecan.
• 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 intervention. Note: Participants who have entered the Follow-up Phase of an investigational study may participate if it has been 4 weeks after the last dose of the previous investigational agent.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.

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Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06341478

Sponsor: IRCCS San Raffaele

Eligibility:

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

Inclusion Criteria:

• Inclusion in NureCombo (NCT04876313), SURE-01 (NCT05226117), and SURE-02 (NCT05535218) clinical trials or candidates to radical cystectomy as per routine clinical practice. 2. Histopathologically-confirmed urothelial carcinoma (UC). 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 4. Clinical stage T2-T4N0M0, muscle-invasive bladder cancer (MIBC)

Exclusion Criteria:

1. Refusal to partecipate to the above studies
2. Unavailability of baseline tumor and blood samples

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Condition: T1 Urinary Bladder Cancer

Study Type: Observational [Patient Registry]

Clinical Trials Identifier NCT 8-digits: NCT05792033

Sponsor: Medical University of Vienna

Phase:

Eligibility:

• Age: minimum 18 Years maximum 90 Years
• Gender: All

Inclusion Criteria:

• Subjects must meet all the following inclusion criteria to participate in this study:
• Pathologically confirmed diagnosis of primary T1 bladder cancer
• Diagnosis of primary T1 bladder cancer is confirmed at 2nd look TURB
• Imaging examinations shows no lymph node metastasis or distant metastasis
• Patients who agree to surgery, and will be effected to the standard postoperative management and follow-up treatment in accordance to current guidelines
• In case of persistent T1 bladder cancer at 2nd look TURB, patient can be included only if detrusor muscle is present in the pathologic specimen

Exclusion Criteria:

• Previous bladder cancer
• Upstaging to MIBC at 2nd look TURB
• Contraindications to surgery (i.e. bladder fibrosis)
• Poor performance status making a surgical intervention too risky
• Life expectancy of less than one year
• Patient refused to participate
• Pregnancy
• Concomitant or history of upper urinary tract urothelial cancer

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Condition: Urinary Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05822934

Sponsor: Assiut University

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• All patients diagnosed with muscle invasive urinary bladder cancer that can receive chemotherapy are included the criteria are
• • Age above 18 years,
• Pathologically proven urinary bladder cancer,
• Patients with clinical stages T2-4a N0-3 M0,
• Patients with good renal and liver functions
• patients with no distant metastases,
• no other malignancy (double malignancy).
• Performance status 0-1 according to ECOG performance status scale.
• Patients with no contraindications for radiotherapy.

Exclusion Criteria:

• • performance status 2-4 according to ECOG performance status scale.
• patients refuse to receive chemotherapy,
• patients not eligible to receive chemotherapy due to liver or renal impairment or thrombocytopenia,
• patients with M1 disease.

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Condition: Urinary Bladder Neoplasms

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT05742867

Sponsor: Bristol-Myers Squibb

Phase:

Eligibility:

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

Inclusion Criteria:

• Must reside in Japan and able to speak/read Japanese for the interview/survey
• Must have a clinical diagnosis of Muscle-invasive bladder cancer (MIBC):
• ypT2-ypT4a or ypN+ MIBC, with prior neoadjuvant cisplatin chemotherapy and underwent radical cystectomy
• pT3-pT4a or pN+ MIBC, without prior neoadjuvant cisplatin chemotherapy and underwent radical cystectomy
• Must not have received any treatment related to MIBC after radical cystectomy

Exclusion Criteria:

• Determined by the physician as being unsuitable for the study (e.g. having any clinically significant psychiatric disorder, cognitive impairment, or having difficulty with communicating in Japanese)
• Confirmed diagnosis of other primary cancers at the time of obtaining consent
• Current participation in a MIBC clinical trial

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Condition: Urinary Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05644041

Sponsor: University of Arizona

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

1. Patients able to consent in English or Spanish; provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female ages ≥18 years.
4. Patients with intermediate or high-risk non-muscle-invasive UC of the bladder and no previous BCG treatment.
5. Histologically confirmed intermediate or high-risk non-muscle invasive urothelial carcinoma of the bladder (Ta, T1, or Tis stage) on Transurethral Resection of Bladder Tumor (TURBT) must be obtained within 180 days of registration. OR Patients with a high-grade recurrence after 24 months since last dose of BCG.
6. Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-
7. Post-transurethral bladder tumor resection.
8. Evidence of post-menopausal status or negative urinary pregnancy test of female pre-menopausal patients is required. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.

Exclusion Criteria:

1. Known hypersensitivity reaction to gemcitabine.
2. Clinical T2 or higher stage UC of the bladder.
3. Histopathology demonstrating any small cell component, pure adenocarcinoma, pure squamous cell carcinoma, or pure CIS of the bladder.
4. Active malignancies other than the disease being treated under study.
5. Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) urothelial carcinoma of any stage.
6. Pregnant or breast-feeding women.
7. Has an underlying substance abuse or psychiatric disorder such that, in the opinion of the investigator, the patient would be unable to comply with the protocol.

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Condition: Urinary Bladder Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04369560

Sponsor: Jodi Maranchie

Phase: Early Phase 1

Eligibility:

• Age: minimum 18 Years maximum 90 Years
• Gender: All

Inclusion Criteria:

1. 18 to 90 years of age
2. Able to understand and willing to sign a written informed consent document
3. A papillary tumor identified by cystoscopy that has been scheduled for TURBT OR histologically proven MIBC that is clinically localized and amenable to surgical resection with curative intent.
4. Performance status of ECOG 0 or 1
5. Normal renal function as defined as creatinine less than 1.5 x institutional upper limit of normal (ULN) OR creatinine clearance greater than or equal to 50 mL/min/1.73 m2 by Cockcroft-Gault formula for subjects with creatinine levels greater than or equal to 1.5 x ULN.

Exclusion Criteria:

1. Severe hypersensitivity reaction to gadobutrol or ferumoxytol.
2. Severe claustrophobia that will prevent completion of the MRI study.
3. Any MRI-non-compatible implanted device, prosthetic or pacemaker.
4. Known or suspected metastatic disease.
5. Women with active pregnancy, lactation or plans to conceive
6. Untreated urinary tract infection
7. Known urethral stricture disease that would prohibit placement of foley catheter.
8. Any other conditions considered as unacceptable risk by the treating physician

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Condition: Urinary Bladder Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04658862

Sponsor: Janssen Research & Development, LLC

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• Ineligible for or have elected not to undergo radical cystectomy
• All adverse events associated with any prior surgery and/or intravesical therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade less than (<) 2 prior to randomization
• Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
• Thyroid function tests are within the normal range per investigator assessment (or stable on hormone supplementation). Investigators may consult an endocrinologist for participant eligibility assessment in the case of equivocal or marginal test results
• Adequate bone marrow, liver, and renal function: Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding two weeks): Absolute neutrophil count (ANC) greater than or equal to (>=) 1,500/cubic millimeters (mm^3); Platelet count >=80,000/mm^3; Hemoglobin >=9.0 grams per deciliter (g/dL); Liver function: (Total bilirubin less than or equal to (<=) 1.5 * upper limit of normal (ULN) or direct bilirubin <= ULN for participants with total bilirubin levels greater than (>)1.5*ULN (except participants with Gilbert's Syndrome, who must have a total bilirubin < 3.0 mg/dL), and Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (<=) 2.5* institutional ULN); Renal function: Creatinine clearance >=30 mL/min using the Cockcroft-Gault formula. 24-hour creatinine clearance test will also be accepted for estimating renal function in situations where Cockcroft-Gault formula is not a good predictor of estimating adequate renal function

Exclusion Criteria:

• Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder. Ta/T1/Carcinoma in situ (CIS) of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to initiating study
• Must not have diffuse CIS based on cystoscopy and biopsy. Diffuse, or multi-focal, CIS is defined as the presence of at least 4 distinct CIS lesions in the bladder at the time of the Screening re-TURBT
• Participants must not have evidence of cT4b, or N1-3, or M1 disease based on local radiology staging (chest, abdomen, and pelvis must be performed using Computed tomography [CT] or Magnetic resonance imaging [MRI]) within 42 days prior to randomization
• Presence of any bladder or urethral anatomic feature that, in the opinion of the investigator, may prevent the safe placement, indwelling use, or removal of TAR 200
• Evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has healed prior to randomization

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Condition: Urinary Bladder Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04919512

Sponsor: Janssen Research & Development, LLC

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

• Histologically proven, cT2-T4a N0, M0 infiltrating urothelial carcinoma of the bladder. Initial diagnosis must have been within 120 days of randomization date. Participants with variant histologic subtypes are allowed if tumor(s) demonstrate urothelial predominance. However, the presence of small cell or neuroendocrine variants will make a participant ineligible
• Participants with no residual tumor, or intravesical tumor size of less than or equal to (<=)3 centimeter (cm) following transurethral resection of bladder tumor (TURBT) are eligible; debulking TURBT for any residual disease is encouraged but not mandated. Participants with persistent tumors greater than (>)3 cm at screening must undergo a second debulking, re-staging TURBT. Participants will be ineligible if any individual tumor is >3 cm after debulking TURBT
• Deemed eligible for and willing to undergo RC by the operating urologist
• Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 or 1
• Thyroid function tests within normal range or stable on hormone supplementation per investigator assessment. Investigators may consult an endocrinologist for participant eligibility assessment in the case of equivocal or marginal tests results
• All adverse events associated with any prior surgery must have resolved to common terminology criteria for adverse events (CTCAE) version 5.0 Grade less than (<) 2 prior to randomization

Exclusion Criteria:

• Must not have received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment
• Participants must not have evidence of cT4b, or N1-3, or M1 disease based on central radiology staging (chest, abdomen, and pelvis must be performed using computed tomography [CT] or magnetic resonance imaging [MRI]) within 42 days prior to randomization
• Presence of any bladder or urethral anatomic feature that, in the opinion of the Investigator, may prevent the safe placement, indwelling use, or removal of TAR-200
• Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time
• Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to enrollment
• Participants with evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has resolved prior to dosing

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Condition: Muscle-invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04660344

Sponsor: Hoffmann-La Roche

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• for the Surveillance Phase:
• Histologically confirmed MIUC (also termed TCC) of the bladder
• TNM classification (based on AJCC Cancer Staging Manual, 8th Edition; Amin et al. 2016) at pathological examination of surgical resection specimen as follows: For patients treated with prior NAC: tumor stage of ypT2-4a or ypN+ and M0. For patients who have not received prior NAC: tumor stage of pT2-4a or pN+ and M0
• Surgical resection of MIUC of the bladder
• Patients who have received prior platinum-based NAC.
• Patients who have not received prior platinum-based NAC, have refused, are ineligible ("unfit") for cisplatin-based adjuvant chemotherapy, or will not receive based on physicisan's decision.
• ctDNA assay developed based on tumor tissue specimen and matched normal DNA from blood.
• Tumor PD-L1 expression per IHC that is evaluable by central testing of a representative tumor tissue specimen.
• Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pelvis, abdomen, and chest no more than 4 weeks prior to enrollment.
• Full recovery from cystectomy and enrollment within 24 weeks following cystectomy. Minimum of 6 weeks must have elapsed from surgery. Additional Inclusion Criteria for the Treatment Phase:
• Blood for plasma ctDNA sample evaluated to be ctDNA positive, defined as the presence of two or more mutations out of the 16 mutations identified based on patient's WES evaluable (ctDNA assay designability) report
• Absence of residual disease and absence of metastasis, as confirmed by a negative baseline CT or MRI scan of the pelvis, abdomen, and chest no more than 28 days prior to randomization, as assessed by the investigator
• ECOG Performance Status of <= 2
• Life expectancy >=12 weeks
• Adequate hematologic and end-organ function, investigator decision
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs General Medical Exclusion Criteria for the Surveillance Phase:
• Known PD-L1 IHC result for adjuvant therapy. The decision for the adjuvant therapy should not be based on the PD-L1 IHC result. If a cap is in effect limiting enrollment of PD-L1 negative patients, this exclusion criterion will not apply.
• Pregnancy or breastfeeding
• Positive test for HIV, with the following exception: Patients with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy, have a CD4 count >= 200/µL, and have an undetectable viral load
• Patients with active hepatitis B virus or hepatitis C. Patients with past HBV infection or resolved HBV infection are eligible. A negative HBV DNA test must be obtained in these patients prior to enrollment. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Active tuberculosis confirmed by a test performed within 3 months prior to treatment initiation.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• History of autoimmune disease. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina Cancer-Specific Exclusion Criteria for the Surveillance Phase:
• Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to study enrollment
• Adjuvant chemotherapy or radiation therapy for UC following cystectomy
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or 5 half-lives of the drug, whichever is longer, prior to enrollment
• Malignancies other than UC within 5 years prior to study enrollment Additional

Exclusion Criteria:

• for the Surveillance Phase:
• Known PD-L1 IHC result for adjuvant therapy. The decision for the adjuvant therapy should not be based on the PD-L1 IHC result. If a cap is in effect limiting enrollment of PD-L1 negative patients, this exclusion criterion will not apply.
• Pregnancy or breastfeeding
• Positive test for HIV, with the following exception: Patients with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy, have a CD4 count >= 200/µL, and have an undetectable viral load
• Patients with active hepatitis B virus or hepatitis C. Patients with past HBV infection or resolved HBV infection are eligible. A negative HBV DNA test must be obtained in these patients prior to enrollment. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Active tuberculosis confirmed by a test performed within 3 months prior to treatment initiation.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• History of autoimmune disease. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina Cancer-Specific Exclusion Criteria for the Surveillance Phase:
• Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to study enrollment
• Adjuvant chemotherapy or radiation therapy for UC following cystectomy
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or 5 half-lives of the drug, whichever is longer, prior to enrollment
• Malignancies other than UC within 5 years prior to study enrollment Additional Exclusion Criteria for the Treatment Phase:
• Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to randomization to the treatment phase Hormone-replacement therapy or oral contraceptives are allowed.
• Adjuvant chemotherapy or radiation therapy for UC following cystectomy
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or 5 half-lives of the drug, whichever is longer, prior to randomization to the treatment phase
• Positive test for HIV, with the following exception: Patients with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy, have a CD4 count >= 200/μL, and have an undetectable viral load.
• Patients with active hepatitis B virus or hepatitis C
• Active tuberculosis confirmed by a test performed within 3 months prior to treatment initiation

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Condition: Muscle Invasive Bladder Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma AJCC v6 and v7, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Stage IV Bladder Urothelial Carcinoma AJCC v7

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05987241

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2/Phase 3

Eligibility:

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

Inclusion Criteria:

• PRE-REGISTRATION: Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Variant histology, including neuroendocrine differentiation, is allowed if urothelial cancer is predominant histology (any amount of squamous differentiation is allowed provided the tumor is not a pure squamous cell cancer)
• PRE-REGISTRATION: Patient must have had radical cystectomy and lymph node dissection >= 3 weeks, but =< 12 weeks prior to pre-registration. Patients who have had a partial cystectomy as definitive therapy are not eligible
• PRE-REGISTRATION: No gross cancer at the surgical margins. Microscopic invasive urothelial carcinoma at the surgical margins (i.e., "positive margins") are allowed. Carcinoma in situ (CIS) at margins is considered negative margins
• PRE-REGISTRATION: No evidence of residual cancer or metastasis after cystectomy (imaging is not required prior to pre-registration but is required prior to registration)
• PRE-REGISTRATION: Have undergone a radical cystectomy with pathological evidence of urothelial carcinoma of the bladder at high risk of recurrence as described in one of the two scenarios below (i or ii). The 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized.:
• (i) Patients who have not received neoadjuvant cisplatin-based chemotherapy: pT3-pT4* or pT0/x-pT4/N+ on cystectomy and are not eligible for adjuvant cisplatin chemotherapy
• (i) Patients ineligible for cisplatin due to at least one of the following criteria and reason for ineligibility should be documented:
• (i) Creatinine Clearance (using Cockcroft-Gault): < 60 mL/min
• (i) Common Terminology Criteria for Adverse Events (CTCAE) version 5, grade >= 2 audiometric hearing loss
• (i) CTCAE version 5, grade >= 2 or above peripheral neuropathy
• New York Heart Association Class III heart failure
• (i) Eastern Cooperative Oncology Group (ECOG) performance status = 2
• (i) Patients who are eligible for cisplatin may be candidates if they refuse available adjuvant chemotherapy, despite being informed by the investigator about the treatment options. The patient's refusal must be documented.
• (i) Patients with pT2N0 urothelial cancer on cystectomy (without prior neoadjuvant chemotherapy) with ctDNA(+) Signatera results based on an assay performed post-cystectomy as part of routine care outside of the study may proceed with pre-registration but require confirmation of ctDNA(+) Signatera testing on repeat "central testing" in the context of A032103 testing. Patients with pT2N0 with central testing not confirming ctDNA(+) will not be eligible for A032103 (Note: this is distinct from patients with ypT2N0 who are eligible based on ii).
• (ii) Patients who received cisplatin-based neoadjuvant chemotherapy: ypT2-ypT4 or ypT0/x-pT4/N+ on cystectomy
• PRE-REGISTRATION: Available tumor tissue for central Signatera testing to be submitted after pre-registration. Central testing is defined as testing performed as part of the A032103 study prior to registration and is provided by the study and not routine standard commercial testing. Patients who have already had Signatera testing performed as part of routine care will require repeat central testing as part of the A032103 study to be eligible for registration/randomization. Tumor tissue from the cystectomy is preferred over tissue from prior transurethral resection
• PRE-REGISTRATION: Age >= 18 years
• PRE-REGISTRATION: ECOG Performance Status 0-2
• PRE-REGISTRATION: Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
• PRE-REGISTRATION: No postoperative/adjuvant systemic therapy after cystectomy
• PRE-REGISTRATION: No adjuvant radiation after cystectomy
• PRE-REGISTRATION: No treatment with any other type of investigational agent =< 4 weeks before pre-registration
• PRE-REGISTRATION: Not have ever received prior treatment with PD-1/PD-L1 blockade.
• PRE-REGISTRATION: Not have ever received prior treatment with LAG-3 blockade.
• PRE-REGISTRATION: 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
• PRE-REGISTRATION: Absolute Neutrophil Count (ANC) >= 1,200/mm^3
• PRE-REGISTRATION: Platelet count >= 100,000/mm^3
• PRE-REGISTRATION: Hemoglobin >= 8 g/dL
• PRE-REGISTRATION: Creatinine =< 1.5 x upper limit of normal (ULN) or calculated (calc.) creatinine clearance > 30 mL/min (using either Cockcroft-Gault formula or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
• PRE-REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN
• PRE-REGISTRATION: Total bilirubin =< 1.5 x upper limit of normal (ULN) (except in patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
• PRE-REGISTRATION: For women of childbearing potential only: A negative urine or serum pregnancy test done =< 14 days prior to pre-registration is required
• PRE-REGISTRATION: Not currently requiring hemodialysis
• PRE-REGISTRATION: No current or prior history of myocarditis
• PRE-REGISTRATION: No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens- Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease.
• PRE-REGISTRATION: Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible.
• PRE-REGISTRATION: Patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
• PRE-REGISTRATION: No current pneumonitis or prior history of non-infectious pneumonitis that required steroids within the previous 5 years.
• PRE-REGISTRATION: No known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected).
• PRE-REGISTRATION: 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. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• PRE-REGISTRATION: Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible.
• PRE-REGISTRATION: No concurrent antineoplastic therapy.
• PRE-REGISTRATION: No current immunosuppressive agents (with the exception of corticosteroids as described below).
• PRE-REGISTRATION: No condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of pre-registration (with the exception of steroid pre-medications for contrast allergies). Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• REGISTRATION: Patient must have had radical cystectomy and lymph node dissection =< 18 weeks prior to registration.
• REGISTRATION: Must have evaluable ctDNA Signatera assay result (i.e., ctDNA[+]or ctDNA[-]) based on test performed as part of central testing after pre-registration to A032103. Central testing is defined as testing performed as part of the A032103. Local/commercial testing results may not be used for registration to A032103
• Cisplatin-ineligible (or cisplatin-declining) patients with a pT2N0 urothelial cancer on cystectomy who were pre-registered based on routine standard care ctDNA(+) Signatera testing must have confirmed ctDNA(+) Signatera testing on central testing. If central Signatera testing yields a ctDNA(-) result, these patients are ineligible. NOTE: This is a distinct consideration from patients with ypT2-4 and/or ypN+ urothelial cancer (i.e., patients who had received neoadjuvant cisplatin-based chemotherapy) who are eligible with either ctDNA(+) or ctDNA(-) central Signatera testing
• REGISTRATION: All patients must have confirmed disease-free status defined as no measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or definitive non-measurable radiographic metastatic disease, within 60 days prior to registration. Patients with equivocal nodes less than 15 mm in short axis, or < 10 mm in long axis for non-lymph node lesions, not considered by the investigator to represent malignant disease will be eligible. Attempts should be made to resolve the etiology of equivocal lesions with complementary imaging (e.g., PET scan) or biopsy.
• REGISTRATION: No major surgery =< 3 weeks before registration.
• REGISTRATION: No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette- Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist [registered trademark]) are live attenuated vaccines and are not allowed. Coronavirus disease 2019 (COVID-19) vaccines are not live vaccines and are allowed
• COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
• Patient must have converted to ctDNA(+) during serial monitoring performed centrally in the setting of the A032103 study
• COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
• No evidence of metastatic disease on the most recent scheduled imaging assessment as outlined in the study calendar (no repeat imaging is necessary specifically at the time of the conversion from ctDNA[-] to ctDNA[+]).
• COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
• No change in clinical condition and/or laboratory tests that would impact the safety of nivolumab in the opinion of the treating investigator
• COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
• =< 6 weeks from reporting of ctDNA(+) result by Natera.

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Condition: Bladder Carcinoma, Ureter Carcinoma, Renal Pelvis Carcinoma, Non-small Cell Lung Cancer, Invasive Breast Carcinoma, Cutaneous Melanoma, Esophageal Carcinoma, Gastroesophageal Junction Carcinoma, Gastric Adenocarcinoma, Pancreatic Adenocarcinoma, Squamous Cell Carcinoma of the Head and Neck, Epithelial Ovarian Carcinoma, Fallopian Tube Carcinoma, Endometrial Carcinoma, Renal Cell Carcinoma

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT05059444

Sponsor: Guardant Health, Inc.

Phase:

Eligibility:

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

Inclusion Criteria:

• Age > 18 years old AND
• Were treated with curative intent AND
• Are planning to undergo regular follow-up and monitoring for cancer recurrence per standard of care at the enrolling site AND
• Provided written informed consent to participate in the study AND
• Are willing to have de-identified clinical data shared with investigators at regular intervals as outlined in the study protocol and informed consent AND
• Are willing to provide blood samples at enrollment and at subsequent clinical visits coinciding with standard of care follow-up, for up to 5 years as outlined in the study protocol and informed consent AND
• Have at least one blood sample collected 4-12 weeks after completion of primary treatment of the Index Cancer
• Have a histologically confirmed Index Cancer that qualifies for inclusion, defined as: Primary Study Cohorts
• Cohort 1: Muscle invasive carcinoma of the bladder, ureter, or renal pelvis (stage II-III),
• Cohort 2: Non-small cell lung cancer (stage II-III),
• Cohort 3: Invasive breast carcinoma with all of the following: Clinical stage T1-4/N0-3/M0 at presentation AND Completed preoperative systemic chemotherapy-containing regimen AND Underwent definitive surgical resection of the primary tumor AND Has pathological evidence of residual invasive carcinoma in the breast and/or axillary lymph nodes AND Hormone receptor and HER2 status are known Exploratory Cohorts
• Cohort 4: Stage IIb-III cutaneous melanoma or limited (resectable) stage IV melanoma treated with curative intent,
• Cohort 5: Esophageal or gastroesophageal junction carcinoma (stage II-III),
• Cohort 6: Gastric adenocarcinoma (stage II-III),
• Cohort 7: Surgically resected pancreatic adenocarcinoma,
• Cohort 8: Invasive squamous cell carcinoma of the head and neck (includes stage I-III oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, nasal cavity, paranasal sinus, and salivary gland cancers),
• Cohort 9: High-risk epithelial ovarian or Fallopian tube carcinoma (defined as stage IC-III or stage I that has high grade (grade 3-4) or clear cell histology),
• Cohort 10: High-risk endometrial carcinoma (defined as having any of the following: serous or clear cell adenocarcinoma histology (any stage), grade 3 or 4 deeply invasive (T1b or greater) endometrioid carcinoma, stage III disease (any histology)),
• Cohort 11: High-risk renal cell carcinoma (defined as high grade (grade 3-4) stage II, stage III or limited (resectable) stage IV treated with curative intent)

Exclusion Criteria:

• History of allogeneic organ or tissue transplant
• Index cancer has neuroendocrine histology
• History of another primary cancer, with the exception of the following (if adequately treated and the patient is without evidence of disease at the time of enrollment): in situ cancers, non-melanoma skin carcinoma, localized low-risk prostate cancer (Gleason score < 6) with PSA in the normal range, and stage I papillary thyroid carcinoma.
• Known distant metastasis at time of enrollment (with the exception of participants with limited/resectable stage IV cutaneous melanoma or RCC)
• Is participating in a clinical trial or another observational study that is evaluating the performance of another genomic test in the post-treatment surveillance setting at predicting/detecting recurrence

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Condition: Muscle Invasive Bladder Urothelial Carcinoma, Muscle-Invasive Bladder Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06257017

Sponsor: Yung NA

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum 70 Years
• Gender: All

Inclusion Criteria:

• 1. aged 18-70 years old; 2. a score of ≤1 for the Eastern Cooperative Oncology Group (ECOG) Performance Status; 3. receiving radical cystectomy (with lymph node dissection) or nephroureterectomy; 4. histologically confirmed (surgical specimen) muscle invasive urothelial carcinoma, and the major histological type should be transitional cell carcinoma; 5. Classification of tumour, node and metastasis (TNM): pT2-4a N0-2M0; 6. absence of microscopic (i.e., positive margin) or gross residual of the tumor (R0 resection) and absence of metastasis, confirmed by a negative CT or MRI scan of pelvis, abdomen and chest within 4 weeks prior to enrolment; 7. adequate hematologic and end-organ function, defined by the following laboratory results obtained within 28 days prior to the first study treatment:
• ANC≥1500 cells/μL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
• WBC counts > 2500 cells/μL
• Lymphocyte count ≥ 300 cells/μL
• Platelet count ≥ 100,000 cells/μL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
• Hemoglobin ≥ 9.0 g/dL
• AST, ALT, and alkaline phosphatase ≤ 2.5 × the upper limit of normal (ULN),
• PTT ≤ 1.5 × ULN
• PT ≤ 1.5 × ULN or INR < 1.7
• Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula) 8. able to understand and provide written informed consent, and agree to receive the treatment arrangement and study procedures stated in the informed consent

Exclusion Criteria:

1. receiving any approved anti-cancer treatment within 3 weeks prior to study enrolment;
2. participation in another clinical trial with therapeutic intent within 28 days prior to enrolment;
3. suffering from malignancies other than urothelial carcinoma within 5 years prior to study enrolment;
4. conditions that contraindicate chemotherapy, such as renal impairment with creatinine clearance rate (CCr) <50 mL/min, hearing impairment, and inadequate marrow function;
5. anaphylactic or hypersensitivity reactions or other contraindication to cisplatin and gemcitabine;
6. active or uncontrolled infections, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or tuberculosis;
7. pregnancy or breastfeeding.

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Condition: Non Muscle Invasive Bladder Cancer, Urologic Cancer, Bladder Cancer, Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT06111235

Sponsor: CG Oncology, Inc.

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• Pathologically confirmed IR-NMIBC, per American Urologic Association/Society of Urologic Oncology/National Comprehensive Cancer Network guidelines, within 90 days of participant randomization: 1. Recurrent LG Ta within 12 months of prior LG or HG (HG Ta ≤ 3 cm) tumor 2. Solitary LG Ta >3 cm tumor 3. Multifocal LG Ta tumors 4. Primary and solitary HG Ta ≤3 cm tumor 5. LG T1 tumor
• All visible disease removed by TURBT within 12 weeks of study randomization
• Acceptable baseline organ function

Exclusion Criteria:

• High-risk NMIBC (e.g., HG T1, Recurrent or multifocal HG Ta>3cm tumor(s), CIS)
• Low-Risk NMIBC (e.g., solitary LG Ta ≤3 cm tumor)
• Disease in the prostatic urethra at any time or in the upper genitourinary tract within 24 months of randomization
• Muscle-invasive bladder cancer, locally advanced or metastatic bladder cancer
• Prior treatment with any human adenovirus serotype 5 based therapy (e.g., Ad-interferon or Adstiladrin)

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Condition: Non-muscle Invasive Bladder Cancer, NMIBC, Carcinoma in Situ of Bladder, Bladder Cancer, Urothelial Carcinoma Bladder, Urothelial Carcinoma Recurrent

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05375903

Sponsor: UroGen Pharma Ltd.

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

• 1. Able to give informed consent. 2. Arm A: Have confirmed recurrent NMIBC with HG Ta and/or T1 disease and/or CIS or recurrent IR LG Ta and/or T1 disease. Arm B: Have confirmed recurrent NMIBC with HG Ta and/or T1 disease and/or CIS. Arm C: Have confirmed recurrent NMIBC with HG Ta and/or T1 disease and/or CIS. 3. Patients with HG Ta and/or T1 disease and/or CIS must meet one of the following criteria: • Have Bacillus Calmette-Guérin (BCG)-unresponsive disease, defined as 1) persistent or recurrent CIS alone or with recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy, or 2) recurrent HG Ta/T1 disease within 6 months of completion of adequate BCG therapy, or 3) HG T1 disease at the first evaluation following a BCG induction course. Notes: Adequate BCG therapy is defined as at least 5 of 6 doses of an initial induction course plus 1) at least 2 of 3 doses of maintenance therapy or 2) at least 2 of 6 doses of a second induction course. Patients with BCG-unresponsive disease also must be unwilling or unfit to undergo radical cystectomy.
• Have otherwise failed adequate BCG therapy (eg, recurrence > 6 months [papillary] or > 12 months [CIS] after last BCG exposure).
• Are BCG intolerant, defined as the inability to tolerate at least one full induction course of BCG.
• Have HG Ta disease with tumors ≤ 3 cm and failed at least one previous course of therapy (eg, adjuvant intravesical chemotherapy). 4. Have all papillary tumors visible by white light resected, and obvious areas of CIS fulgurated during Screening or within 6 weeks before Screening. Note: Blue light cystoscopy is not permitted. 5. Eastern Cooperative Oncology Group (ECOG) status ≤ 2. 6. Absence of concomitant upper tract urothelial carcinoma (UTUC) or urothelial carcinoma (UC) within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumor by either intravenous pyelogram, retrograde pyelogram, computerized tomography (CT) urogram with or without contrast, or magnetic resonance imaging (MRI) urogram with or without contrast performed within 6 months of enrollment. 7. Patients with prostate cancer on active surveillance at very low, low, or intermediate risk for progression, defined as Gleason Grade Group 1 or 2, Gleason score ≤ 7, with prostate-specific antigen < 20 ng/dL, and cT1-cT2b (NCCN, 2023) are permitted to be in the study at the discretion of the investigator (see exclusion criterion 8). 8. Female patients of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for 1 month following the last administration of study drug and must have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female patients must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile. "Maximally effective birth control" means that the patient, if sexually active, should be using a combination of 2 methods of birth control that are approved and recognized to be effective by health authorities. 9. Male patients must be surgically sterile or willing to use 2 highly effective forms of birth control upon enrollment, during the course of the study, and for 1 month following the last study drug instillation. 10. Has adequate organ and bone marrow function within 14 days of treatment initiation as determined by routine laboratory tests outlined below:
• Leukocytes ≥ 3,000/μL;
• Absolute neutrophil count (ANC) ≥ 1,500/μL;
• Platelets ≥ 100,000/μL;
• Hemoglobin ≥ 9.0 g/dL;
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN);
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN;
• Alkaline phosphatase (ALP) ≤ 2.5 × ULN;
• Estimated creatinine clearance ≥ 30 mL/min calculated using the Cockcroft-Gault equation. 11. Has a life expectancy > 12 months.

Exclusion Criteria:

1. Current or previous evidence of muscle invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (ie, T2, T3, T4 and/or stage IV).
2. Current systemic therapy for bladder cancer.
3. Prior therapy with an anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1), anti-PD-ligand 1 (L1) agent, or with an agent directed to another co-inhibitory T-cell receptor.
4. Active infection requiring systemic therapy including urinary tract infection (once satisfactorily treated, patients can enter the study).
5. Active systemic autoimmune disease that required systemic treatment in the past 2 years. Short courses of steroids (≤ 14 days) for medical reasons without anticancer intent (eg, atopic dermatitis, psoriasis, infection, allergic reaction) are permitted if the last dose was ≥ 4 weeks before the first dose of study treatment.
6. Women who are pregnant or nursing.
7. Any medical psychological, familial, sociological, or geographical condition that, in the opinion of the Investigator, would preclude participation in the study.
8. History of malignancy of other organ system within the past 5 years, except previously treated UTUC, basal cell carcinoma or squamous cell carcinoma of the skin, and/or prostate cancer under active surveillance (see inclusion criterion 8).
9. Patients who cannot tolerate intravesical dosing or intravesical surgical manipulation.
10. Intravesical therapy within 4 weeks before starting study treatment.
11. Has participated in a study of an investigational agent and received study therapy or received investigational device within 4 weeks before the first dose of study treatment.
12. Has received an immune modulator therapy within 5 half-lives of starting study treatment.
13. Has received a vaccine within 2 weeks before starting study treatment.
14. Has a known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

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