Study of Sacituzumab Govitecan in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread (TROPHY U-01)
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| ClinicalTrials.gov Identifier: NCT03547973 |
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Recruitment Status :
Recruiting
First Posted : June 6, 2018
Last Update Posted : April 23, 2024
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Sponsor:
Gilead Sciences
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
Gilead Sciences
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Urothelial Cancer | Drug: Sacituzumab Govitecan-hziy Drug: Pembrolizumab Drug: Cisplatin Drug: Avelumab Drug: Zimberelimab Drug: Carboplatin Drug: Gemcitabine Drug: Domvanalimab | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 643 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase II Open-Label Study of Sacituzumab Govitecan in Unresectable Locally Advanced/Metastatic Urothelial Cancer |
| Actual Study Start Date : | August 13, 2018 |
| Estimated Primary Completion Date : | July 2024 |
| Estimated Study Completion Date : | July 2026 |
Resource links provided by the National Library of Medicine
Drug Information
available for:
Sacituzumab govitecan
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort 1: Sacituzumab Govitecan-hziy
Participants with urothelial cancer (UC) previously treated with platinum-based and/or checkpoint inhibitors (CPIs) will receive sacituzumab govitecan-hziy 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle.
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Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
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Experimental: Cohort 2: Sacituzumab Govitecan-hziy
Participants with UC who are ineligible for platinum-based therapy and failed therapy with previous immune CPI therapy will receive sacituzumab govitecan-hziy 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle.
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Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
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Experimental: Cohort 3: Sacituzumab Govitecan-hziy + 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 sacituzumab govitecan-hziy 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 sacituzumab govitecan-hziy may be tested based on dose-limiting toxicities (DLTs) observed to determine the Recommended Phase 2 Dose (RP2D) of sacituzumab govitecan-hziy in combination with pembrolizumab.
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Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
Drug: Pembrolizumab Administered per package insert
Other Name: KEYTRUDA® |
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Experimental: Cohort 4: Sacituzumab Govitecan-hziy + 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.
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Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
Drug: Cisplatin Administered per package insert Drug: Avelumab Administered per package insert
Other Name: BAVENCIO® |
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Experimental: Cohort 4: Sacituzumab Govitecan-hziy + Cisplatin + Zimberelimab (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).
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Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
Drug: Cisplatin Administered per package insert Drug: Zimberelimab Administered intravenously |
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Experimental: Cohort 5 (Arm 1): Sacituzumab Govitecan-hziy + 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, 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. |
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
Drug: Zimberelimab Administered intravenously |
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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 Q2W until PD, unacceptable toxicity, or loss of clinical benefit. |
Drug: Avelumab
Administered per package insert
Other Name: BAVENCIO® |
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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. |
Drug: Zimberelimab
Administered intravenously |
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Experimental: Cohort 6 (Arm 1): 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.
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Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
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Experimental: Cohort 6 (Arm 2): Sacituzumab Govitecan-hziy + 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.
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Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
Drug: Zimberelimab Administered intravenously |
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Experimental: Cohort 6 (Arm 3): Sacituzumab Govitecan-hziy + ZIM + 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.
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Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
Drug: Zimberelimab Administered intravenously Drug: Domvanalimab Administered intravenously |
|
Experimental: Cohort 6 (Arm 4): Carboplatin + 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. |
Drug: Avelumab
Administered per package insert
Other Name: BAVENCIO® Drug: Carboplatin Administered per package insert Drug: Gemcitabine Administered per package insert |
Primary Outcome Measures :
- 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)) ]ORR will be defined as the rate of the best overall response as Complete Remission (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 only) [ Time Frame: 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.
Secondary Outcome Measures :
- Overall Response Rate (ORR) [ Time Frame: 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, and 5. ORR will also be evaluated based on investigator review by Modified RECIST 1.1 for Immune-Based Therapeutics (iRECIST 1.1) for Cohort 3 only.
- Duration of Response (DOR) [ Time Frame: 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 Cohort 3 only.
- Progression-Free Survival (PFS) [ Time Frame: 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 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 Cohort 3 only.
- Overall Survival (OS) [ Time Frame: 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 to death from any cause.
- Clinical Benefit Rate (CBR) [ Time Frame: 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, and 5. CBR will also be evaluated based on investigator review by iRECIST 1.1 for Cohort 3 only.
- Cohorts 3, 4, and 5: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: First dose date up to last dose date plus 30 days (approximately 3 years) ]
- Cohorts 3, 4, and 5: Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities [ Time Frame: First dose date up to last dose date plus 30 days (approximately 3 years) ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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.
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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.
- 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.
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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.
- 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03547973
Contacts
| Contact: Gilead Clinical Study Information Center | 1-833-445-3230 (GILEAD-0) | GileadClinicalTrials@gilead.com |
Locations
Show 135 study locations
Sponsors and Collaborators
Gilead Sciences
Merck KGaA, Darmstadt, Germany
Investigators
| Study Director: | Gilead Study Director | Gilead Sciences |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Gilead Sciences |
| ClinicalTrials.gov Identifier: | NCT03547973 |
| Other Study ID Numbers: |
IMMU-132-06 2018-001167-23 ( EudraCT Number ) 2023-508302-24 ( Other Identifier: European Medicines Agency ) |
| First Posted: | June 6, 2018 Key Record Dates |
| Last Update Posted: | April 23, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Carboplatin Gemcitabine Pembrolizumab Avelumab Sacituzumab govitecan Antineoplastic Agents Antimetabolites, Antineoplastic |
Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Immune Checkpoint Inhibitors Immunoconjugates Immunologic Factors Physiological Effects of Drugs |