Study of Sacituzumab Govitecan in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread
- Conditions
- Metastatic Urothelial Cancer
- Interventions
- Registration Number
- NCT03547973
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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).
- Detailed Description
Non-Randomized for Cohorts 1,2,3, and 4; Randomized for Cohorts 5 and 6. Cohort 5 has been cancelled, effective December 2023.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 643
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:
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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.
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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.
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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.
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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.
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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).
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Cohorts 4, 5, 6: Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
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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.
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No evidence of progressive disease following completion of first-line chemotherapy (ie, CR, PR, or SD per RECIST v1.1 guidelines as per investigator).
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Treatment-free interval of 4 to 10 weeks since the last dose of chemotherapy.
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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.
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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.
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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 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1: Sacituzumab Govitecan-hziy (SG) Sacituzumab Govitecan-hziy 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. Cohort 6 (Arm 3): SG + ZIM + Domvanalimab (DOM) Domvanalimab 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. Cohort 7 (Phase 1: Safety Lad-in and Dose Expansion): SG + Enfortumab Vedotin (EV) + ZIM Zimberelimab 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. Cohort 2: SG Sacituzumab Govitecan-hziy 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. Cohort 3: SG + Pembrolizumab Sacituzumab Govitecan-hziy 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. Cohort 4: SG + Cisplatin + Avelumab (Dose Escalation Phase) Cisplatin 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. Cohort 3: SG + Pembrolizumab 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. Cohort 4: SG + Cisplatin + Zimberelimab (ZIM) (Dose Expansion Phase) Sacituzumab Govitecan-hziy 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). Cohort 4: SG + Cisplatin + Avelumab (Dose Escalation Phase) Sacituzumab Govitecan-hziy 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. Cohort 4: SG + Cisplatin + Avelumab (Dose Escalation Phase) Avelumab 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. Cohort 4: SG + Cisplatin + Zimberelimab (ZIM) (Dose Expansion Phase) Cisplatin 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). Cohort 4: SG + Cisplatin + Zimberelimab (ZIM) (Dose Expansion Phase) Zimberelimab 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). Cohort 5 (Arm 2): Avelumab 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. Cohort 5 (Arm 1): SG + ZIM Sacituzumab Govitecan-hziy 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. Cohort 5 (Arm 1): SG + ZIM Zimberelimab 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. Cohort 6 (Arm 1): SG Sacituzumab Govitecan-hziy 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. Cohort 6 (Arm 3): SG + ZIM + Domvanalimab (DOM) Sacituzumab Govitecan-hziy 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. Cohort 5 (Arm 3): ZIM Zimberelimab 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. Cohort 6 (Arm 2): SG + ZIM Sacituzumab Govitecan-hziy 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. Cohort 6 (Arm 2): SG + ZIM Zimberelimab 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. Cohort 6 (Arm 3): SG + ZIM + Domvanalimab (DOM) Zimberelimab 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. Cohort 6 (Arm 4): Carboplatin (CARBO) + Gemcitabine (GEM) Avelumab 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. Cohort 6 (Arm 4): Carboplatin (CARBO) + Gemcitabine (GEM) Gemcitabine 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. Cohort 6 (Arm 4): Carboplatin (CARBO) + Gemcitabine (GEM) Carboplatin 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. Cohort 7 (Phase 1: Safety Lad-in and Dose Expansion): SG + Enfortumab Vedotin (EV) + ZIM Enfortumab Vedotin 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. Cohort 7 (Phase 2: Arm 1): SG + EV + ZIM Sacituzumab Govitecan-hziy 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. Cohort 7 (Phase 2: Arm 2): EV + ZIM Enfortumab Vedotin Upon completion of the Cohort 7 dose-expansion phase, participants will receive EV 1.25 mg/kg IV and ZIM 360 mg IV. Cohort 7 (Phase 1: Safety Lad-in and Dose Expansion): SG + Enfortumab Vedotin (EV) + ZIM Sacituzumab Govitecan-hziy 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. Cohort 7 (Phase 2: Arm 1): SG + EV + ZIM Zimberelimab 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. Cohort 7 (Phase 2: Arm 2): EV + ZIM Zimberelimab Upon completion of the Cohort 7 dose-expansion phase, participants will receive EV 1.25 mg/kg IV and ZIM 360 mg IV. Cohort 7 (Phase 2: Arm 3): Optional Dose Optimization SG + EV + ZIM Sacituzumab Govitecan-hziy 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. Cohort 7 (Phase 2: Arm 1): SG + EV + ZIM Enfortumab Vedotin 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. Cohort 7 (Phase 2: Arm 3): Optional Dose Optimization SG + EV + ZIM Zimberelimab 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. Cohort 7 (Phase 2: Arm 3): Optional Dose Optimization SG + EV + ZIM Enfortumab Vedotin 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 Measures
Name Time Method 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) Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date)) ORR will be defined as the rate of the best overall response as Complete Response (CR) or Partial Response (PR) and based on central review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria.
Progression free survival (PFS) Based on Central Review by RECIST 1.1 criteria (Cohort 5) Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date)) PFS will be defined as the time from first dose until objective tumor progression, as assessed based on central review, or death, whichever comes first.
ORR Based on Investigator Review by RECIST 1.1 Criteria (Cohort 7) Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date)) ORR will be defined as the rate of the best overall response as Complete Response (CR) or Partial Response (PR) and based on investigator review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria.
Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) (Cohort 7) First dose date up to last dose date plus 30 days (approximately 3 years) Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities (Cohort 7) First dose date up to last dose date plus 30 days (approximately 3 years)
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date)) ORR will be defined as the rate of the best overall response as CR or PR and based on investigator review by RECIST 1.1 criteria for cohorts 3, 4, 6, and 7. ORR will also be evaluated based on investigator review by Modified RECIST 1.1 for Immune-Based Therapeutics (iRECIST 1.1) for Cohorts 3, 4, 6, and 7.
Duration of Response (DOR) Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date)) DOR will be calculated from the date of the first evaluation showing documented response, PR, or CR, to the date of the first disease progression or death and based on central and investigator review by RECIST 1.1 criteria for all cohorts. DOR will also be evaluated based on investigator review by iRECIST 1.1 for Cohorts 3, 4, 6, and 7.
Progression-Free Survival (PFS) Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date)) PFS is defined as the time from the first dose (Cohorts 1 through 4) or randomization date (Cohorts 5 through 7) until objective tumor progression,or death, whichever comes first and based on central and investigator review by RECIST 1.1 criteria for all cohorts. PFS will also be evaluated based on investigator review by iRECIST 1.1 for Cohorts 3, 4, 6, and 7.
Overall Survival (OS) Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date)) OS will be measured from the date of first dose (Cohorts 1 through 4) or randomization date (Cohorts 5 through 7) to death from any cause.
Clinical Benefit Rate (CBR) Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date)) CBR is defined as CR + PR + Stable Disease (SD) for at least 6 months and based on central and investigator review by RECIST 1.1 criteria for Cohorts 3, 4, 6, and 7. CBR will also be evaluated based on investigator review by iRECIST 1.1 for Cohorts 3, 4, 6, and 7.
Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) (Cohorts 3, 4, 5, and 6) First dose date up to last dose date plus 30 days (approximately 3 years) Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities (Cohorts 3, 4, 5, and 6) First dose date up to last dose date plus 30 days (approximately 3 years)
Trial Locations
- Locations (135)
Hospital Universitario Puera de Hierro Majadahonda
🇪🇸Majadahonda, Spain
CEIC Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
The University of Arizona Cancer Center-North Campus
🇺🇸Tucson, Arizona, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Centers
🇺🇸Littleton, Colorado, United States
Smilow Cancer Hospital at Yale-New Haven
🇺🇸New Haven, Connecticut, United States
Eastern Connecticut Hematology and Oncology Associates
🇺🇸Norwich, Connecticut, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Woodlands Medical Specialists, PA
🇺🇸Pensacola, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Norton Cancer Institute, Downtown
🇺🇸Louisville, Kentucky, United States
Maryland Oncology Hematology, P.A.
🇺🇸Brandywine, Maryland, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
University of Illinois Cancer Center
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Southern Illinois University School of Medicine, Simmons Cancer Institute
🇺🇸Springfield, Illinois, United States
Oncology Hematology West PC dba Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Precision Cancer Research / New Mexico Oncology & Hematology Consultants
🇺🇸Albuquerque, New Mexico, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
🇺🇸New York, New York, United States
Drug Shipping Address: New York-Presbyterian Hospital
🇺🇸New York, New York, United States
Stony Brook Cancer Center
🇺🇸Stony Brook, New York, United States
St. Luke's Hosptial - Bethlehem Campus
🇺🇸Easton, Pennsylvania, United States
Medical University of Southern Carolina
🇺🇸Charleston, South Carolina, United States
Thompson Oncology Group - Knoxville West
🇺🇸Knoxville, Tennessee, United States
Henry-Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
Houston Methodist Hospital, Houston Methodist Cancer Center
🇺🇸Houston, Texas, United States
Mays Cancer Center
🇺🇸San Antonio, Texas, United States
Renovatio Clinical
🇺🇸The Woodlands, Texas, United States
University of Utah - Huntsman Cancer Hospital (IP Shipping Address)
🇺🇸Salt Lake City, Utah, United States
Centre Jean Perrin
🇫🇷Clermont Ferrand Cedex, France
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Virginia Oncology Associates
🇺🇸Hampton, Virginia, United States
Oncology Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care
🇺🇸Roanoke, Virginia, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University of Wisconsin Clinical Science Center
🇺🇸Madison, Wisconsin, United States
Centre Hospitalier Regional Universitaire (CHRU) de Besancon, Hopital Jean Minjoz
🇫🇷Besançon, France
Hopital Saint Andre (CHU de Bordeaux)
🇫🇷Bordeaux, France
Centre Hospitalier Regional Universitaire Brest
🇫🇷Brest, France
Centre Hospitalier Departmental (CHD) Vendee
🇫🇷La Roche sur Yon, France
Centre Oscar Lambret
🇫🇷Lille, France
Centre Leon Berard
🇫🇷Lyon Cedex 08, France
Institut Paoli Calmettes
🇫🇷Marseille CEDEX 9, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Centre Hospitalier Universitaire De Nimes - Hopital Universitaire Caremeau
🇫🇷Nîmes cedex, France
Hopital European Georges-Pompidou (HEGP)
🇫🇷Paris Cedex 15, France
Groupement Hospitalier Pitie-Salpetriere
🇫🇷Paris, France
Hopital Cochin
🇫🇷Paris, France
Centre Eugene Marquis
🇫🇷Rennes Cedex, France
Centre Hospitalier Prive Saint-Gregoire
🇫🇷Rennes, France
CHU de Rouen
🇫🇷Rouen, France
Hospitaux Universitaires de Strasbourg - Hopital Civil
🇫🇷Strasbourg, France
Hospital Foch
🇫🇷Suresnes, France
Institut Claudius Regaud
🇫🇷Toulouse Cedex 9, France
Institut de Cancerologie de Lorraine
🇫🇷Vandoeuvre les Nancy, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Urologicum Duisburg
🇩🇪Duisburg, Germany
Centrum fur Hamatologie und Onkologie Bethanien
🇩🇪Frankfurt, Germany
Universitätsklinikum Frankfurt, Klinik für Urologie
🇩🇪Frankfurt, Germany
Universitatsklinikum Freiburg
🇩🇪Freiburg, Germany
Universitatsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
University Hospital Heidelberg
🇩🇪Heidelberg, Germany
Marien Hospital Herne
🇩🇪Herne, Germany
Universitatsklinikum Jena
🇩🇪Jena, Germany
Institut für Versorgungsforschung in der Onkologie
🇩🇪Koblenz, Germany
Universitätsklinikum Magdeburg
🇩🇪Magdeburg, Germany
Universitätsklinikum Carl Gustav Carus an der TU Dresden
🇩🇪Mainz, Germany
Klinikum rechts der Isar der Technischen Universität München, Urologische Klinik und Poloklinik
🇩🇪München, Germany
Universitatsklinikum Munster, Klinik fur Urologie und Kinderurologie
🇩🇪Münster, Germany
Universitat Regensburg
🇩🇪Regensburg, Germany
Universitatsklinikum Tubingen, Klinik fur Urologie
🇩🇪Tübingen, Germany
Ospedale San Donato
🇮🇹Arezzo, Italy
Henry Dunant Hospital Center, 4th Oncology Department
🇬🇷Athens, Greece
Anassa General Clinic, Oncology-Chemotherapy Department
🇬🇷Volos, Greece
University General Hospital of Ioannina, Oncology Department
🇬🇷Ioannina, Greece
Athens Medical Center, Oncology Department
🇬🇷Marousi, Greece
ASST Cremona
🇮🇹Cremona, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
General Hospital of Patras Agios Andreas
🇬🇷Patra, Greece
Centro di Riferimento Oncologico IRCCS
🇮🇹Aviano, Italy
Ospedale Policlinico San Martino IRCCS
🇮🇹Genoa, Italy
Istituto Romagnolo per Io Studio dei Tumori (IRST) "Dino Amadori"
🇮🇹Meldola, Italy
Azienda Ospedaliero Universitaria Maggiore della Carita
🇮🇹Novara, Italy
Istituto Oncologico Veneto IRCCS - Ospedale Busonera
🇮🇹Padova, Italy
Azienda Ospedaliero-Universitaria Pisana
🇮🇹Pisa, Italy
Instituto Nazionale Tumori Regina Elena - IFO
🇮🇹Roma, Italy
Azienda Ospedaliera Santa Maria di Temi
🇮🇹Terni, Italy
Centro Ricerche Cliniche di Verona srl
🇮🇹Verona, Italy
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Korea, Republic of
Korea University - Anam Hospital
🇰🇷Seongbuk-Gu, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Yonsei University Health System, Severance Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
SMG-SNU Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, St. Vincent's Hospital
🇰🇷Suwon-si, Korea, Republic of
Yonsei University - Wonju Severance Christian Hospital
🇰🇷Wonju-si, Korea, Republic of
Pusan National University Yangsan Hospital
🇰🇷Yangsan, Korea, Republic of
Institut Catala d'Oncologia Badalona - Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
Complejo Hospitalario Universitario Insular Materno Infantil
🇪🇸Las Palmas, Spain
MD Anderson Cancer Centre
🇪🇸Madrid, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Sant Joan de Deu
🇪🇸Manresa, Spain
Complejo Hospitalario de Ourense
🇪🇸Orense, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Complejo Hospitalario Universitario de Santiago
🇪🇸Santiago de Compostela, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Ankara Sehir Hastanesi
🇹🇷Ankara, Turkey
Dicle Universitesi Tip Fakultesi Hastanesi
🇹🇷Diyarbakir, Turkey
Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi
🇹🇷Edrine, Turkey
Istanbul Universitesi Cerrahpasa Tip Fakultesi Hastanesi
🇹🇷Istanbul, Turkey
Medipol Mega Universite Hastanesi
🇹🇷Istanbul, Turkey
T.C. Saglik Bakanligi Goztepe Prof Dr. Suleyman Yalcin Sehir Hastanesi
🇹🇷Istanbul, Turkey
Izmir Medical Point Hastanesi, Medikal Onkoloji Departmant
🇹🇷Izmir, Turkey
Baskent Universitesi Adana Dr.Turgut Noyan Uygulama ve Arastima Merkezi
🇹🇷Seyhan, Turkey
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Barts Health NHS Trust
🇬🇧London, United Kingdom
East and North Hertfordshire NHS Trust
🇬🇧Northwood, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧Surrey, United Kingdom