Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Sacituzumab Govitecan-hziy in Metastatic Urothelial Cancer (TROPHY U-01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03547973
Recruitment Status : Recruiting
First Posted : June 6, 2018
Last Update Posted : September 24, 2021
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
The objective of this study is to evaluate the efficacy and safety of sacituzumab govitecan-hziy 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 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 321 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Open Label, Study of IMMU-132 in Metastatic Urothelial Cancer After Failure of Platinum-Based Regimen or Anti-PD-1/ PD-L1 Based Immunotherapy
Actual Study Start Date : August 13, 2018
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™

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.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™

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.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™

Drug: Pembrolizumab
Administered per package insert
Other Name: KEYTRUDA®

Experimental: Cohort 4: Sacituzumab Govitecan-hziy + Cisplatin + 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.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™

Drug: Cisplatin
Administered per package insert

Drug: Avelumab
Administered per package insert
Other Name: BAVENCIO®

Experimental: Cohort 5: Sacituzumab Govitecan-hziy + Cisplatin + 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 RP2D determined in Cohort 4 on Days 1 and 8 of a 21-day cycle, and avelumab 800 mg every 2 weeks beginning on Cycle 1, Day 1 and every 2 weeks. For participants who have not progressed after completion of up to 6 cycles of sacituzumab govitecan-hziy, cisplatin, and avelumab, maintenance therapy will be permitted with 800 mg of avelumab every 2 weeks and sacituzumab govitecan-hziy at the 10 mg/kg dose on Days 1 and 8 every 21 days. Maintenance therapy can start 4 to 6 weeks after the last dose of induction chemotherapy and will be permitted to continue until loss of clinical benefit.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™

Drug: Cisplatin
Administered per package insert

Drug: Avelumab
Administered per package insert
Other Name: BAVENCIO®




Primary Outcome Measures :
  1. Overall Response Rate (ORR) Based on Central Review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria. [ 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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) ]
  7. 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Participants 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.
  • Cohorts 4 and 5: 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).
  • Adequate renal and hepatic function.
  • Adequate hematologic parameters without transfusional support.
  • Individuals must have a 3-month life expectancy.
  • Have measurable disease by Computed Tomography Imaging (CT) or Magnetic Resonance Imaging (MRI) as per RECIST 1.1 criteria.

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 (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Requires concomitant medication interfering with ABCA1 transporter or UGT1A1
  • 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
  • Cohorts 3 to 5: Has active autoimmune disease requiring systemic treatment with steroids or other immunosuppressive agent or any condition that in the Investigator's judgment precludes treatment with pembrolizumab, 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, has received anti-PD-1/PD-L1 therapy previously
  • Cohorts 4 and 5: Refractory to platinum (i.e., relapsed ≤ 12 months after completion of chemotherapy) in the neoadjuvant/adjuvant setting.

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
Layout table for location contacts
Contact: Gilead Clinical Study Information Center 1-833-445-3230 (GILEAD-0) GileadClinicalTrials@gilead.com

Locations
Show Show 35 study locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Layout table for investigator information
Study Director: Gilead Study Director Gilead Sciences
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT03547973    
Other Study ID Numbers: IMMU-132-06
2018-001167-23 ( EudraCT Number )
First Posted: June 6, 2018    Key Record Dates
Last Update Posted: September 24, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Pembrolizumab
Avelumab
Antineoplastic Agents
Antineoplastic Agents, Immunological