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TROPHY-U-01 Cohort 2: A Phase II Study of Sacituzumab Govitecan in Cisplatin-Ineligible Patients With Metastatic Urothelial Cancer Progressing After Previous Checkpoint Inhibitor Therapy

Purpose: Sacituzumab govitecan (SG) is a Trop-2–directed antibody-drug conjugate with an SN-38 payload, approved for patients with locally advanced (LA) or metastatic urothelial cancer (mUC) who progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report results from Cohort 2 of TROPHY-U-01 trial, evaluating the efficacy and safety of SG in patients with mUC.

Methods: TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label phase II study. Cohort 2 includes patients with LA or mUC who have had progression or recurrence after a CPI and were cisplatin-ineligible at study initiation. Patients received SG 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end point was objective response rate (ORR) per central review; secondary end points were clinical benefit rate (CBR), duration of response (DOR), and progression-free survival (PFS) per central review and safety.

Results: Cohort 2 included 38 patients (61% male; median age 72.5 years; 66% visceral metastases [29% liver]; 50% received previous PT-based chemotherapy as previous [neo]adjuvant therapy]). At a median follow-up of 9.3 months, ORR was 32% (95% CI, 17.5 to 48.7), CBR 42% (95% CI, 26.3 to 59.2), median DOR 5.6 months (95% CI, 2.8 to 13.3), median PFS 5.6 months (95% CI, 4.1 to 8.3), and median overall survival 13.5 months (95% CI, 7.6 to 15.6). Grade ≥3 treatment-emergent adverse events occurred in 87% of patients, most commonly neutropenia (34%), anemia (24%), leukopenia (19%), fatigue (18%), and diarrhea (16%).

Conclusion: SG monotherapy demonstrated a relatively high ORR with rapid responses; this was feasible with a manageable toxicity profile in cisplatin-ineligible patients who had progression after CPI therapy. Limitations include a moderate sample size and lack of random assignment. These results warrant further evaluation of SG alone and in combinations in patients with LA/mUC.

Daniel P. Petrylak, MD,1 Scott T. Tagawa, MD,2 Rohit K. Jain, MD,3 Manojkumar Bupathi, MD,4 Arjun Balar, MD,5 Arash Rezazadeh Kalebasty, MD,6 Saby George, MD,7 Phillip Palmbos, MD, PhD,8 Luke Nordquist, MD, FACP,9 Nancy Davis, MD,10 Chethan Ramamurthy, MD,11 Cora N. Sternberg, MD,12 Yohann Loriot, MD, PhD,13 Neeraj Agarwal, MD,14 Chandler Park, MD,6,15 Julia Tonelli, MD,16 Morganna Vance, DO,16 Huafeng Zhou, PhD,17 and Petros Grivas, MD, PhD18

  1. Yale School of Medicine, New Haven, CT
  2. Weill Cornell Medical College of Cornell University, New York, NY
  3. H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
  4. Rocky Mountain Cancer Centers, Littleton, CO
  5. New York University Langone Medical Center, New York, NY
  6. University of California, Irvine, Orange, CA
  7. Roswell Park Comprehensive Cancer Center, Buffalo, NY
  8. University of Michigan, Ann Arbor, MI
  9. Urology Cancer Center, Omaha, NE
  10. Vanderbilt-Ingram Cancer Center, Nashville, TN
  11. University of Texas Health Science Center at San Antonio, San Antonio, TX
  12. Weill Cornell Medical College of Cornell University, New York, NY
  13. Institut de Cancérologie Gustave Roussy, Université Paris-Saclay, Villejuif, France
  14. Huntsman Cancer Institute, Salt Lake City, UT
  15. University of California, Irvine, Orange, CA
  16. Norton Cancer Institute, Louisville, KY
  17. Gilead Sciences, Inc, Parsippany, NJ
  18. University of Washington, Fred Hutchinson Cancer Center, Seattle, WA
Source: Petrylak DP., Tagawa ST., Jain RK. et al. TROPHY-U-01 Cohort 2: A Phase II Study of Sacituzumab Govitecan in Cisplatin-Ineligible Patients With Metastatic Urothelial Cancer Progressing After Previous Checkpoint Inhibitor Therapy. Journal of Clinical Oncology. 2024. https://doi.org/10.1200/JCO.23.01720.