Summary

Objectives

Eligibility

1. Key Inclusion Criteria: Inclusion Criteria for All Cohorts: - Female or male individuals, = 18 years of age (19 Years old for South Korea). - Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1. - Adequate renal and hepatic function. - Adequate hematologic parameters without transfusional support. - Individuals must have a 3-month life expectancy. Additional Inclusion Criteria for Cohorts 1 to 6: - Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin): - Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease; - Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive urothelial cancer, with recurrence/progression =12 months following completion of therapy. - Cohort 1: In addition to above criterion, have had progression or recurrence of urothelial cancer following receipt of an Anti-programmed Cell Death Protein 1 (anti-PD-1)/ Anti-programmed Death Ligand 1 (PD-L1) therapy. - Cohort 2: Were ineligible for platinum-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease with anti-PD-1/PD-L1 therapy. Individual may not have received any platinum for treatment of recurrent, metastatic or advanced disease. - Cohort 3: Progression or recurrence of UC following a platinum containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy. - Cohort 4: Individual has not received any platinum-based chemotherapy in the metastatic or unresectable locally advanced setting. Creatinine clearance of at least 50 mL/min calculated by Cockcroft-Gault formula or another validated tool. For individuals receiving cisplatin at 70 mg/m^2 on Day 1 of every 21-day cycle, a creatinine clearance of least 60 mL/min calculated by Cockcroft -Gault formula or another validated tool is required. Individuals with creatinine clearance between 50 to 59 mL/min are to receive a split dose of cisplatin (35 mg/m^2 Day 1 and Day 8 of every 21-day cycle). - Cohorts 4, 5, 6: Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma. - Cohort 5: Individuals received at least 4 cycles and no more than 6 cycles of GEM + cisplatin. No other chemotherapy regimens are allowed in this cohort, with the exception of prior adjuvant or neoadjuvant systemic therapy with curative intent after > 12 months from completion of therapy. - No evidence of progressive disease following completion of first-line chemotherapy (ie, CR, PR, or SD per RECIST v1.1 guidelines as per investigator). - Treatment-free interval of 4 to 10 weeks since the last dose of chemotherapy. - Cohort 6: Cis-ineligible and no prior therapy for metastatic disease or for unresectable locally advanced disease. Checkpoint inhibitor therapy naïve or >12 months from completion of adjuvant therapy are permitted. - Cohorts 4 and 6: Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. - Cohorts 1, 2, 3 and 5: Creatinine clearance = 30 mL/min as calculated by the Cockcroft-Gault formula unless otherwise specified Additional Inclusion Criteria for Cohort 7: - No prior systemic therapy for locally advanced or metastatic UC. Therapy in the curative setting is allowed provided recurrence is > 12 months since the last dose of systemic therapy. - Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma. - Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Key Exclusion Criteria: Exclusion Criteria for All cohorts: - Females who are pregnant or lactating. - Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. - Has an active second malignancy. - Has known active Hepatitis B or Hepatitis C. - Has other concurrent medical or psychiatric conditions. - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. - Has an active second malignancy. Additional Exclusion Criteria for Cohorts 1 to 6: - For Cohort 5: Alopecia, sensory neuropathy Grade =2 is acceptable, or other Grade << 2 adverse events not constituting a safety risk based on the investigator's judgment are acceptable. - Cohort 3: Has received anti-PD-1/PD-L1 therapy previously. - Cohorts 3 to 6: Has an active autoimmune disease that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. - Cohorts 3 to 6: Has received a live vaccine within 30 days prior to the first dose of study drug(s), has history or evidence of interstitial lung disease (ILD) or non-infectious pneumonitis. - Cohort 4: Refractory to platinum (i.e., relapsed = 12 months after completion of chemotherapy) in the neoadjuvant/adjuvant setting. - Cohorts 4, 5, and 6: For individuals who received prior CPI, a treatment-free interval >12 months between the last treatment administration and the date of recurrence is required. Additional Exclusion Criteria for Cohort 7: - Have had a prior anticancer therapy within 12 months prior to C1D1 or prior radiation therapy within 2 weeks prior to C1D1. Individuals participating in observational studies are eligible. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of investigational product. - Have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. - Have a Child-Pugh score of B or C. - Individuals with uncontrolled diabetes. - Have active keratitis or corneal ulcerations. - Participants with ongoing sensory or motor neuropathy Grade = 2. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Treatment Sites in Georgia