Phase I/II Study of Avelumab in Combination With AXL Inhibitor AVB-S6-500 in Patients With Advanced Urothelial Carcinoma

Condition: Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04004442

Sponsor: University of Oklahoma

Phase: Phase 2


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

Inclusion Criteria:

  1. Age ≥18 years
  2. Histologically confirmed locally advanced unresectable (T4b or N2/N3 disease) or metastatic urothelial cancer (including renal pelvis, ureters, urinary bladder, urethra).
  3. Eligible patients must have had either:
  4. Progressed after treatment with at least 1 prior platinum-containing regimen, (e.g., received at least 2 cycles of cisplatin or carboplatin-based regimen) for inoperable locally advanced unresectable or metastatic urothelial carcinoma, OR
  5. Unable to tolerate platinum (cisplatin or carboplatin) based chemotherapy due to toxicity, OR
  6. Experienced disease progression or recurrence within 12 months of completion of neoadjuvant or adjuvant cisplatin-based chemotherapy, OR
  7. Ineligible for cisplatin-based chemotherapy due to eastern co-operative oncology group (ECOG) performance status 2, grade ≥2 neuropathy, GFR<60 mL/Hr, grade ≥2 hearing loss and New York Heart Association class III or worse congestive heart failure.
  8. Available pretreatment baseline tumor specimen or willingness to undergo biopsy of primary or metastatic lesion if archived specimen is not available.
  9. ECOG performance status of ≤2
  10. At least one measurable lesion by RECIST version 1.1
  11. Patients who are able to understand and sign the informed consent form.
  12. Ability to comply with protocol
  13. Adequate hematologic and end-organ function per protocol
  14. For women of childbearing potential: Negative serum or urine pregnancy test at screening.
  15. For both male and female subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 30 days after the last dose of study drug

Exclusion Criteria:

  1. Concurrent systemic treatment with an anticancer treatment or investigational drug within 28 days. Palliative radiation to symptomatic primary tumor or metastases is permitted as long as there are other measurable lesions present outside of the radiation field.
  2. Prior therapy with anti-PD-1 or PD-L1 agents.
  3. Concurrent systemic therapy with corticosteroids (>10 mg prednisone equivalent) or other immunosuppressive agents within 28 days before starting trial drug. Short-term administration of systemic steroids (less than 7 days), adrenal replacement steroid doses (≤10 mg daily prednisone equivalent), topical, intranasal and inhaled steroid use is permitted.
  4. Patients with untreated or symptomatic central nervous metastases will be excluded. Appropriately treated CNS metastases with either surgery or radiation therapy are permitted to participate in the study.
  5. Active second malignancy or previous history of malignant disease (other than urothelial carcinoma) diagnosed within the last 3 years, with the exclusion of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ and prostate adenocarcinoma with Gleason score ≤7, pT2b.
  6. Prior organ transplantation, including allogenic stem-cell transplantation.
  7. Known history of testing positive for HIV/AIDS, HBV, or HCV (including acute and chronic infection).
  8. Known hypersensitivity to monoclonal antibody or any biologic drug, history of anaphylaxis, or uncontrolled asthma.
  9. Persisting toxicity related to prior therapy that was > grade 1; grade ≤2 sensory neuropathy is allowed.
  10. Pregnant or lactating, or intending to become pregnant during the study a. Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative pregnancy test result within 14 days prior to the first dose of study treatment.
  11. Diagnosis of active autoimmune disease requiring systemic immunosuppression. Patients with type 1 diabetes, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring systemic immunosuppression are eligible.
  12. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  13. Active infection requiring systemic therapy.
  14. Severe infections within 4 weeks prior to the first dose of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  15. Administration of a live/attenuated vaccine within 4 weeks prior to the first dose of study treatment, within 5 months following the administration of the last dose of study drug, or anticipation that such a live/attenuated vaccine will be required during the study.
  16. Other severe acute or chronic medical conditions per protocol

View trial on