Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3

Author(s): Petros Grivas, MD, PhD1; Damien Pouessel, MD, PhD2; Chandler H. Park, MD3; Philippe Barthelemy, MD, PhD4; Manojkumar Bupathi, MD, MS5; Daniel P. Petrylak, MD6; Neeraj Agarwal, MD7; Sumati Gupta, MD7; Aude Fléchon, MD, PhD8; Chethan Ramamurthy, MD9; Nancy B. Davis, MD10; Alejandro Recio-Boiles, MD, FACP11; Cora N. Sternberg, MD12; Astha Bhatia, MPH, DMD13; Cabilia Pichardo, MD13; Mitch Sierecki, MD13; Julia Tonelli, MD13; Huafeng Zhou, MD13; Scott T. Tagawa, MD, MS12; Yohann Loriot, MD, PhD14
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Both medications are approved as a single agent in second-filine therapy, and now the combination seems to be promising with manageable toxicity. Overall Response Rate (ORR): 41%
I think we need phase 3 data to show superiority over single agent therapy.
And now with pembrolizumab used in first-line therapy, this regimen may disappear.


Pembrolizumab is standard therapy for patients with metastatic urothelial cancer (mUC) who progress after first-line platinum-based chemotherapy; however, only approximately 21% of patients respond. Sacituzumab govitecan (SG) is a trophoblast cell surface antigen-2–directed antibody-drug conjugate with US Food and Drug Administration–accelerated approval to treat patients with locally advanced or mUC who previously received platinum-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report the primary analysis of TROPHY-U-01 cohort 3.


TROPHY-U-01 ( identifier: NCT03547973) is a multicohort, open-label phase II study. Patients were CPI-naïve and had mUC progression after platinum-based chemotherapy in the metastatic setting or ≤12 months in the (neo)adjuvant setting. Patients received 10 mg/kg of SG once on days 1 and 8 and 200 mg of pembrolizumab once on day 1 of 21-day cycles. The primary end point was objective response rate (ORR) per central review. Secondary end points included clinical benefit rate (CBR), duration of response (DOR) and progression-free survival (PFS) per central review, and safety.


Cohort 3 included 41 patients (median age 67 years; 83% male; 78% visceral metastases [29% liver]). With a median follow-up of 14.8 months, the ORR was 41% (95% CI, 26.3 to 57.9; 20% complete response rate), CBR was 46% (95% CI, 30.7 to 62.6), median DOR was 11.1 months (95% CI, 4.8 to not estimable [NE]), and median PFS was 5.3 months (95% CI, 3.4 to 10.2). The median overall survival was 12.7 months (range, 10.7-NE). Grade ≥3 treatment-related adverse events occurred in 61% of patients; most common were neutropenia (37%), leukopenia (20%), and diarrhea (20%).


SG plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with mUC who progressed after platinum-based chemotherapy. No new safety signals were detected. These data support further evaluation of SG plus CPI in mUC.

Author Affiliations

1Fred Hutchinson Cancer Center, University of Washington, Seattle, WA; 2Department of Medical Oncology & Clinical Research Unit, Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse (IUCT-Oncopôle), Toulouse, France; 3Norton Cancer Institute, Louisville, KY; 4Institut de Cancérologie Strasbourg Europe, Strasbourg, France; 5Rocky Mountain Cancer Centers, Littleton, CO; 6Yale School of Medicine, New Haven, CT; 7Huntsman Cancer Institute, Salt Lake City, UT; 8Centre Léon Bérard, Lyon, France; 9University of Texas Health Science Center at San Antonio, San Antonio, TX; 10Vanderbilt-Ingram Cancer Center, Nashville, TN; 11University of Arizona Cancer Center, Tucson, AZ; 12Weill Cornell Medical College of Cornell University, New York, NY; 13Gilead Sciences, Inc, Morris Plains, NJ; 14Institut de Cancérologie Gustave Roussy, Université Paris-Saclay, Villejuif, France

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis results from a randomised, controlled, phase 3 study

This is a negative study looking at atezolizumab + chemo vs. chemo alone in metastatic urothelial carcinoma. In the same issue, there is a negative study on atezolizumab vs. chemo alone, as well. It does seem that atezolizumab has limited disease activity versus some comparable agents.

Read More »

Nivolumab plus Gemcitabine–Cisplatin in Advanced Urothelial Carcinoma

For metastatic urothelial carcinoma, the combination of nivolumab + gemcitabine (gem) /cisplatin (cis) resulted in an improved overall response rate (ORR) of 58 vs. 43%, progression-free survival (PFS) at 12 months of 34 vs. 22% and higher rates of complete response (CR) at 22 vs. 12%. This is the first study to improve upon the chemotherapy doublet of gem/cis in this disease setting. While an interesting treatment option, this has not yet made it into the NCCN guidelines and pembrolizumab + enfortumab seems to be a better tolerated, non-chemo option that is gaining traction.

Read More »