Primary analysis of TROPHY-U-01 cohort 2, a phase 2 study of sacituzumab govitecan (SG) in platinum (PT)-ineligible patients (pts) with metastatic urothelial cancer (mUC) that progressed after prior checkpoint inhibitor (CPI) therapy.

Authors

Daniel Petrylak

Daniel P. Petrylak

Yale School of Medicine, New Haven, CT

Daniel P. Petrylak , Scott T. Tagawa , Rohit K. Jain , Manojkumar Bupathi , Arjun V. Balar , Arash Rezazadeh , Saby George , Phillip Lee Palmbos , Luke T. Nordquist , Nancy B. Davis , Chethan Ramamurthy , Cora N. Sternberg , Yohann Loriot , Neeraj Agarwal , Chandler H. Park , Julia Tonelli , Morganna Vance , Huafeng Zhou , Petros Grivas

Organizations

Yale School of Medicine, New Haven, CT, Weill Cornell Medical College of Cornell University, New York, NY, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, Rocky Mountain Cancer Centers, Littleton, CO, New York University Langone Medical Center, New York, NY, Norton Cancer Institute, Louisville, KY, Roswell Park Comprehensive Cancer Center, Buffalo, NY, University of Michigan, Ann Arbor, MI, Urology Cancer Center, Omaha, NE, Vanderbilt-Ingram Cancer Center, Nashville, TN, University of Texas Health Science Center at San Antonio, San Antonio, TX, Institut de Cancérologie Gustave Roussy, Université Paris-Saclay, Villejuif, France, Huntsman Cancer Institute, Salt Lake City, UT, Gilead Sciences, Inc, Morris Plains, NJ, University of Washington; Fred Hutchinson Cancer Center, Seattle, WA

Research Funding

Pharmaceutical/Biotech Company
Gilead Sciences, Inc

Background: Pts with PT-ineligible mUC have limited treatment options following CPI therapies; thus, new treatment options are needed. SG is an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to SN-38, a topoisomerase-I inhibitor, via a proprietary hydrolyzable linker. SG received accelerated FDA approval in April 2021 for pts with mUC who progressed after PT and CPI therapies based on the positive results of the pivotal TROPHY-U-01 Cohort 1 study. In Cohort 1, SG demonstrated an objective response rate (ORR) of 27%, a median overall survival (OS) of 10.9 mo, and a manageable safety profile in 113 pts with locally advanced or mUC (Tagawa, et al. J Clin Oncol. 2021). SG demonstrated an ORR of 28% in PT-ineligible pts with mUC who progressed after CPI therapy in preliminary results of the phase 2 TROPHY-U-01 Cohort 2 study (Petrylak et al. J Clin Oncol. 2020). Here, we report the primary analysis of TROPHY-U-01 Cohort 2. Methods: Cohort 2 pts (≥18 y) were PT-ineligible at screening, had ECOG PS 0-1, and creatinine clearance ≥30 mL/min. Pts received 10 mg/kg of SG on D1 and D8 of 21-day continuous cycles. The primary endpoint was ORR per central review by RECIST 1.1. Secondary endpoints included duration of response (DOR) and progression-free survival (PFS), per central review, and OS. Target enrollment was approximately 40 pts. Assuming the second-line ORR of 40%, 40 pts would give a 95% CI with a lower limit of 25% (CI is 0.25 to 0.57) for ORR. Results: As of July 26, 2022, the median follow-up was 9.3 mo (range, 0.5-30.6) for treated pts (N=38); median age, 72.5 y (range, 41-87), 61% male, 50% ECOG PS 1, and 66% visceral metastases (29% liver). Median number of prior therapies was 2 (range, 1-5); 50% received prior (neo)adjuvant PT, 18% received prior enfortumab vedotin, and 3% received prior erdafitinib. Median time since last prior anticancer therapy was 1.6 mo (range, 1-8) and median duration of last prior anticancer therapy was 4.2 mo (range, 1-12). Per central review, ORR was 32% (95% CI, 17.5-48.7; 32% partial response); median DOR was 5.6 mo (95% CI, 2.8-13.3; n=12); and median PFS was 5.6 mo (95% CI, 4.1-8.3). Median time to response was 1.4 mo (range, 1.3-1.5) and median OS was 13.5 mo (95% CI, 7.6-15.6). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 68% of pts; the most common Grade ≥3 TRAEs were neutropenia (34%), anemia (21%), leukopenia (18%), fatigue (18%), and diarrhea (16%). TRAEs resulted in an 18% discontinuation rate. No treatment-related deaths were reported. Conclusions: SG monotherapy demonstrated a high response rate with an overall manageable safety profile in PT-ineligible pts with mUC who progressed after CPI therapy. No new safety signals were observed. These data support further evaluation of SG in pts with mUC post CPI therapy. Clinical trial information: NCT03547973.

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Abstract Details

Meeting

2023 ASCO Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Prostate Cancer and Urothelial Carcinoma

Track

Urothelial Carcinoma,Prostate Cancer - Advanced

Sub Track

Therapeutics

Clinical Trial Registration Number

NCT03547973

Citation

J Clin Oncol 41, 2023 (suppl 6; abstr 520)

DOI

10.1200/JCO.2023.41.6_suppl.520

Abstract #

520

Poster Bd #

C6

Abstract Disclosures