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

Conditions

• Metastatic Urothelial Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Sacituzumab Govitecan-hziy — DRUG
  Administered intravenously.
• Pembrolizumab — DRUG
  Administered per package insert
• Cisplatin — DRUG
  Administered per package insert
• Avelumab — DRUG
  Administered per package insert
• Zimberelimab — DRUG
  Administered intravenously
• Carboplatin — DRUG
  Administered per package insert
• Gemcitabine — DRUG
  Administered per package insert
• Domvanalimab — DRUG
  Administered intravenously
• Enfortumab Vedotin — DRUG
  Administered intravenously

Study Details

The objective of this study is to evaluate the efficacy and safety of sacituzumab govitecan-hziy monotherapy and with novel combinations in participants with metastatic urothelial cancer (mUC).

Key Dates

Start date

Aug 13, 2018

Status verified

Mar 2026

Primary completion

Apr 30, 2030

Completion

Apr 30, 2030

Study Design

Enrollment

827 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort 1: Sacituzumab Govitecan-hziy (SG)
  Participants with urothelial cancer (UC) previously treated with platinum-based and/or checkpoint inhibitors (CPIs) will receive SG 10 mg/kg intravenously (IV) on Days 1 and 8 of a 21-day cycle.
• Experimental: Cohort 2: SG
  Participants with UC who are ineligible for platinum-based therapy and failed therapy with previous immune CPI therapy will receive SG 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle.
• Experimental: Cohort 3: SG + Pembrolizumab
  Participants who have had 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 will receive SG 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle and pembrolizumab at the standard approved dose (200 mg) only on Day 1 of a 21-day cycle. Lower doses of SG may be tested based on dose-limiting toxicities (DLTs) observed to determine the Recommended Phase 2 Dose (RP2D) of SG in combination with pembrolizumab.
• Experimental: Cohort 4: SG + Cisplatin + Avelumab (Dose Escalation Phase)
  Participants with UC who have never received therapy with platinum in the metastatic setting or for unresectable locally advanced disease will first receive cisplatin (either at 70 mg/m\^2 on Day 1 of a 21-day cycle or at a split dose of 35 mg/m\^2 on Days 1 and 8 of a 21-day cycle with a maximum body surface area of 2) and sacituzumab govitecan-hziy with maximum dose of 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle for up to 6 cycles. Based on DLTs observed, two additional lower doses may be tested to determine RP2D of sacituzumab govitecan-hziy in combination with cisplatin. If premature termination of 1 agent occurs due to toxicity, the other agent may be continued to complete up to 6 cycles of therapy. For participants who have not progressed, maintenance therapy will begin with infusions of avelumab 800 mg every 2 weeks beginning on Cycle 1, Day 1 and every 2 weeks thereafter and sacituzumab govitecan-hziy 10 mg/kg on Days 1 and 8 every 21 days.
• Experimental: Cohort 4: SG + Cisplatin + Zimberelimab (ZIM) (Dose Expansion Phase)
  Participants with UC who have never received therapy with platinum in the metastatic setting or for unresectable locally advanced disease will first receive cisplatin (either at 70 mg/m\^2 on Day 1 of a 21-day cycle or at a split dose of 35 mg/m\^2 on Days 1 and 8 of a 21-day cycle with a maximum body surface area of 2) and sacituzumab govitecan-hziy with maximum dose of 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle for up to 6 cycles. If premature termination of 1 agent occurs due to toxicity, the other agent may be continued to complete up to 6 cycles of therapy. For participants who have not progressed, maintenance therapy will begin with infusions of sacituzumab govitecan-hziy 10 mg/kg on Days 1 and 8 every 21 days and zimberelimab 360 mg every 3 weeks (Day 1 of a 21-day cycle).
• Experimental: Cohort 5 (Arm 1): SG + ZIM
  Participants in Cohort 5 will have completed 4 to 6 cycles of gemcitabine (GEM) + cisplatin therapy without PD prior to study entry. The safety lead-in will be conducted, in 6 to 8 participants (treated with SG 10 mg/kg IV on Day 1 and Day 8 of a 21-day cycle + ZIM 360 mg IV every 3 weeks on a 21-day cycle). Upon completion of the safety lead-in, participants will receive SG 10 mg/kg IV on Days 1 and 8 of a 21-day cycle followed by ZIM 360 mg IV, every 3 weeks (Q3W) (Day 1 of a 21-day cycle) until PD, unacceptable toxicity, or loss of clinical benefit. participants who must discontinue 1 agent may continue the other until PD, unacceptable toxicity, or loss of clinical benefit.
• Experimental: Cohort 5 (Arm 2): Avelumab
  Participants in Cohort 5 will have completed 4 to 6 cycles of gemcitabine (GEM) + cisplatin therapy without PD prior to study entry. The safety lead-in will be conducted, in 6 to 8 participants (treated with SG 10 mg/kg IV on Day 1 and Day 8 of a 21-day cycle + ZIM 360 mg IV every 3 weeks on a 21-day cycle). Upon completion of the safety lead-in, participants will be randomized to receive avelumab 800 mg IV every 2 weeks (Q2W) until PD, unacceptable toxicity, or loss of clinical benefit.
• Experimental: Cohort 5 (Arm 3): ZIM
  Participants in Cohort 5 will have completed 4 to 6 cycles of gemcitabine (GEM) + cisplatin therapy without PD prior to study entry. The safety lead-in will be conducted, in 6 to 8 participants (treated with SG 10 mg/kg IV on Day 1 and Day 8 of a 21-day cycle + ZIM 360 mg IV every 3 weeks on a 21-day cycle). Upon completion of the safety lead-in, participants will be randomized to receive ZIM 360 mg IV Q3W (Day 1 of a 21-day cycle) until PD, unacceptable toxicity, or loss of clinical benefit.
• Experimental: Cohort 6 (Arm 1): SG
  Upon completion of the safety lead-in, participants in Cohort 6 will be randomized and SG will be administered in cisplatin-ineligible participants who have never received therapy in the metastatic setting or for unresectable locally advanced disease. Treatment may be discontinued at any time, but participants will continue to be followed for tumor response until progression is documented, and alternate therapy is initiated. If participants discontinue therapy before evidence of radiologic progression, imaging should continue until radiologic progression is documented, if feasible.
• Experimental: Cohort 6 (Arm 2): SG + ZIM
  Upon completion of the safety lead-in, participants in Cohort 6 will be randomized and SG in combination with ZIM will be administered in cisplatin-ineligible participants who have never received therapy in the metastatic setting or for unresectable locally advanced disease. The standard approved dose of SG will be used in combination with ZIM. Treatment may be discontinued at any time, but participants will continue to be followed for tumor response until progression is documented or alternate therapy is initiated. If participants discontinue therapy before evidence of radiologic progression, imaging should continue until radiologic progression is documented, if feasible.
• Experimental: Cohort 6 (Arm 3): SG + ZIM + Domvanalimab (DOM)
  Upon completion of the safety lead-in, participants in Cohort 6 will be randomized and SG in combination with ZIM and DOM will be administered in cisplatin-ineligible participants who have never received therapy in the metastatic setting or for unresectable locally advanced disease.
• Experimental: Cohort 6 (Arm 4): Carboplatin (CARBO) + Gemcitabine (GEM)
  Upon completion of the safety lead-in, participants in Cohort 6 will be randomized and CARBO in combination with GEM will be administered in cisplatin-ineligible participants who have never received therapy in the metastatic setting or for unresectable locally advanced disease. Participants without disease progression as assessed by the investigator after completion of 4 to 6 cycles of therapy may continue with maintenance therapy (avelumab 800 mg every 2 weeks) until loss of clinical benefit.
• Experimental: Cohort 7 (Phase 1: Safety Lad-in and Dose Expansion): SG + Enfortumab Vedotin (EV) + ZIM
  In the safety lead-in phase, participants will receive a starting dose level of SG 7.5 mg/kg IV and starting dose level of EV 1.25 mg/kg IV will be administered on Days 1 and 8 of each 21-day cycle and ZIM 360 mg IV will be administered on Day 1 of each 21-day cycle. In dose-expansion, participants will receive SG IV and EV IV at the RP2Ds on Days 1 and 8 of each 21-day cycle and ZIM 360 mg IV on Day 1 of each 21-day cycle.
• Experimental: Cohort 7 (Phase 2: Arm 1): SG + EV + ZIM
  Upon completion of the Cohort 7 dose-expansion phase, participants will receive SG IV at the RP2D in combination with EV IV at the RP2D, and ZIM 360 mg IV until PD, unacceptable toxicity, or loss of clinical benefit.
• Experimental: Cohort 7 (Phase 2: Arm 2): EV + ZIM
  Upon completion of the Cohort 7 dose-expansion phase, participants will receive EV 1.25 mg/kg IV and ZIM 360 mg IV.
• Experimental: Cohort 7 (Phase 2: Arm 3): Optional Dose Optimization SG + EV + ZIM
  Upon completion of the Cohort 7 dose-expansion phase, participants will receive SG IV at 1 dose level below the RP2D in combination with EV 1.25 mg/kg IV and ZIM 360 mg IV.

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

Central Contacts

• Gilead Clinical Study Information Center
  1-833-445-3230 (GILEAD-0)
  [email protected]

Locations (37)

Find similar trials in Tucson, AZ

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