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

Sponsor

Gilead Sciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03547973

Collaborator

(none)

321

Enrollment

Locations

Arms

94.6

Anticipated Duration (Months)

8.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Anticipated 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 :

Aug 13, 2018

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

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 Names: 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 Names: 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 Names: BAVENCIO®

Outcome Measures

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. [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

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, 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) [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) [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) [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) [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) [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 [First dose date up to last dose date plus 30 days (approximately 3 years)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
2	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
3	Rocky Mountain Cancer Centers	Littleton	Colorado	United States	80120
4	Smilow Cancer Hospital at Yale-New Haven	New Haven	Connecticut	United States	06510
5	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
6	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida	United States	33140
7	Woodlands Medical Specialists, PA	Pensacola	Florida	United States	32503
8	Moffitt Cancer Center	Tampa	Florida	United States	33612
9	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322
10	Norton Cancer Institute, Downtown	Louisville	Kentucky	United States	40202
11	Maryland Oncology Hematology, P.A.	Brandywine	Maryland	United States	20613
12	University of Michigan	Ann Arbor	Michigan	United States	48109
13	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
14	Oncology Hematology West PC dba Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
15	Precision Cancer Research / New Mexico Oncology & Hematology Consultants	Albuquerque	New Mexico	United States	87109
16	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
17	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York	United States	10016
18	Drug Shipping Address: New York-Presbyterian Hospital	New York	New York	United States	10065
19	Stony Brook Cancer Center	Stony Brook	New York	United States	11794
20	St. Luke's Hosptial - Bethlehem Campus	Easton	Pennsylvania	United States	18045
21	Thompson Oncology Group - Knoxville West	Knoxville	Tennessee	United States	37932
22	Henry-Joyce Cancer Clinic	Nashville	Tennessee	United States	37232
23	Houston Methodist Hospital, Houston Methodist Cancer Center	Houston	Texas	United States	77030
24	Mays Cancer Center	San Antonio	Texas	United States	78229
25	Renovatio Clinical	The Woodlands	Texas	United States	77380
26	University of Utah - Huntsman Cancer Hospital (IP Shipping Address)	Salt Lake City	Utah	United States	84112
27	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22903
28	Virginia Oncology Associates	Hampton	Virginia	United States	23666
29	Oncology Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care	Roanoke	Virginia	United States	24014
30	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
31	University of Wisconsin Clinical Science Center	Madison	Wisconsin	United States	53705
32	Centre Leon Berard	Lyon Cedex 08		France	69373
33	Hopital Cochin	Paris		France	75014
34	Hospitaux Universitaires de Strasbourg - Hopital Civil	Strasbourg		France	67200
35	Hospital Foch	Suresnes		France	92150
36	Institut Claudius Regaud	Toulouse Cedex 9		France	31059
37	Institut Gustave Roussy	Villejuif		France	94800

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Gilead Clinical Trials Website

Publications

None provided.

Responsible Party:

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT03547973

Other Study ID Numbers:

IMMU-132-06
2018-001167-23

First Posted:

Jun 6, 2018

Last Update Posted:

Jul 25, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Pembrolizumab

Avelumab

Study Results

No Results Posted as of Jul 25, 2022