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

Source: https://doi.org/10.1200/JCO.22.02835

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.

PURPOSE

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.

METHODS

TROPHY-U-01 (ClinicalTrials.gov 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.

RESULTS

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%).

CONCLUSION

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

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