Brief Title: Sacituzumab Govitecan-hziy in Metastatic Urothelial Cancer

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Overall Response Rate (ORR) Based on Central Review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria (Cohorts 1 to 4 and 6)

Primary Outcome 1 - Timeframe: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))

Primary Outcome 2 - Measure: Progression free survival (PFS) based on central review by RECIST 1.1 criteria (Cohort 5 only)

Primary Outcome 2 - Timeframe: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))

CONDITION

• Metastatic Urothelial Cancer

ELIGIBILITY

Key Inclusion Criteria:
* Female or male individuals, ≥ 18 years of age (19 Years old for South Korea).

- * Individuals with histologically confirmed urothelial cancer (UC).

- * Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1.

- * 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

- * Adequate renal and hepatic function.

- * Adequate hematologic parameters without transfusional support.

- * Individuals must have a 3-month life expectancy.
Key Exclusion Criteria:
* 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 had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (ie, ≤Grade 1 from AEs due to a previously administered agent).

- * 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. - * Requires concomitant medication interfering with UGT1A1 with no alternate option available. - * Has an active second malignancy. - * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. - * Has known active Hepatitis B or Hepatitis C. - * Has other concurrent medical or psychiatric conditions. - * Cohort 3: Has received anti-PD-1/PD-L1 therapy previously. - * Cohorts 3 to 5: 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.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Gilead Study Director

Role: Study Director

Affiliation: Gilead Sciences

Overall Contact

Name: Gilead Study Director

Phone: 1-833-445-3230 (GILEAD-0)

Email: GileadClinicalTrials@gilead.com

LOCATION