Study of Sacituzumab Govitecan in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread

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 receiptof platinum-containing regimen (cisplatin or carboplatin):

1. Received a first-line platinum-containing regimen in the metastatic setting orfor inoperable locally advanced disease;

2. Or received neo/adjuvant platinum-containing therapy for localizedmuscle-invasive urothelial cancer, with recurrence/progression ≤12 monthsfollowing completion of therapy.

• Cohort 1: In addition to above criterion, have had progression or recurrence ofurothelial 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 metastaticdisease and have had progression or recurrence of urothelial cancer after afirst-line therapy for metastatic disease with anti-PD-1/PD-L1 therapy. Individualmay not have received any platinum for treatment of recurrent, metastatic oradvanced disease.

• Cohort 3: Progression or recurrence of UC following a platinum containing regimen inthe metastatic setting, or progression or recurrence of UC within 12 months ofcompletion of platinum-based therapy as neoadjuvant or adjuvant therapy.

• Cohort 4: Individual has not received any platinum-based chemotherapy in themetastatic or unresectable locally advanced setting. Creatinine clearance of atleast 50 mL/min calculated by Cockcroft-Gault formula or another validated tool. Forindividuals receiving cisplatin at 70 mg/m^2 on Day 1 of every 21-day cycle, acreatinine clearance of least 60 mL/min calculated by Cockcroft -Gault formula oranother validated tool is required. Individuals with creatinine clearance between 50to 59 mL/min are to receive a split dose of cisplatin (35 mg/m^2 Day 1 and Day 8 ofevery 21-day cycle).

• Cohorts 4, 5, 6: Archival tumor tissue comprising muscle-invasive or metastaticurothelial 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 theexception of prior adjuvant or neoadjuvant systemic therapy with curative intentafter > 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 forunresectable locally advanced disease. Checkpoint inhibitor therapy naïve or >12months 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 ifprogression has been demonstrated in such lesions.

• Cohorts 1, 2, 3 and 5: Creatinine clearance ≥ 30 mL/min as calculated by theCockcroft-Gault formula unless otherwise specified

Additional Inclusion Criteria for Cohort 7:

• No prior systemic therapy for locally advanced or metastatic UC. Therapy in thecurative setting is allowed provided recurrence is > 12 months since the last doseof 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 lesionssituated in a previously irradiated area are considered measurable if progressionhas 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 studyDay 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse eventsdue 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 carcinomatousmeningitis.

• 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 judgmentare 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 inpast 2 years (ie, with use of disease-modifying agents, corticosteroids, orimmunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, orphysiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency) is not considered a form of systemic treatment.

• Cohorts 3 to 6: Has received a live vaccine within 30 days prior to the first doseof study drug(s), has history or evidence of interstitial lung disease (ILD) ornon-infectious pneumonitis.

• Cohort 4: Refractory to platinum (i.e., relapsed ≤ 12 months after completion ofchemotherapy) in the neoadjuvant/adjuvant setting.

• Cohorts 4, 5, and 6: For individuals who received prior CPI, a treatment-freeinterval >12 months between the last treatment administration and the date ofrecurrence is required.

Additional Exclusion Criteria for Cohort 7:

• Have had a prior anticancer therapy within 12 months prior to C1D1 or priorradiation therapy within 2 weeks prior to C1D1. Individuals participating inobservational studies are eligible. Use of other investigational drugs (drugs notmarketed for any indication) within 28 days or 5 half-lives (whichever is longer) offirst dose of investigational product.

• Have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-inducedpneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screeningchest 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.