A Phase 2, Multicenter, Single-Arm Trial of CV301 in Combination With PD-1/L1 Blockade in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
This is a Phase 2, single-arm, multi-institutional clinical trial designed to study the combination of CV301 with atezolizumab in the first-line treatment of UC not eligible for cisplatin-containing chemotherapy (Cohort 1) and in the second-line treatment of UC previously treated with standard first-line cisplatin-based chemotherapy (Cohort 2).
• Age ≥ 18 years at date of ICF signature having the ability to comply with protocol.
• Histologically or cytologically documented locally advanced (T4b, any N; or any T, N 2-3) or metastatic (M1, Stage IV; or metastatic recurrence after locoregional treatment) UC (including renal pelvis, ureters, urinary bladder, urethra)
∙ Patients with mixed histologies were required to have a dominant transitional cell pattern.
‣ Locally advanced bladder cancer that was inoperable on the basis of involvement of the pelvic sidewall or adjacent viscera (clinical stage T4b) or bulky nodal metastasis (N2-N3).
• Life expectancy ≥ 12 weeks.
• Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions cannot be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy and no other lesions are available for selection as target lesions.
• Demonstrate adequate organ function.
• 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 (i.e., one that results in a low failure rate \[\< 1% per year\] when used consistently and correctly) and to continue its use for 5 months after the last dose of atezolizumab.
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks preferred) or 10-15 unstained slides, with an associated pathology report.
• For Cohort 1:
• Untreated with chemotherapy
• Have at least one of the following:
∙ ECOG (Eastern Cooperative Oncology Group) performance status of 2.
‣ Glomerular filtration rate calculated as creatinine clearance (Cockroft-Gault formula) of ≥20 mL/min and less than 60 mL/min
‣ Hearing loss or neuropathy of any cause Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2
• For Cohort 2:
⁃ Disease progression during or following treatment with at least one platinum-containing regimen (e.g., GC, MVAC, CarboGem, carboplatin-paclitaxel) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence, as defined by:
• Regimen is defined as patients receiving at least one cycle of a platinum-containing regimen with response assessment. Patients who received one cycle of a platinum-containing regimen but discontinued due to toxicity are also eligible.
∙ Patients who received prior adjuvant/neoadjuvant chemotherapy and progressed within 12 months of treatment with a platinum-containing adjuvant/neoadjuvant regimen are considered as second-line patients.
⁃ ECOG (Eastern Cooperative Oncology Group) performance status of \< 2
⁃ Calculated creatinine clearance (Cockroft-Gault formula) of ≥20 mL/min