TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors
METHODS TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label, phase II, registrational study. Cohort 1 includes patients with locally advanced or unresectable or mUC who had progressed after prior PLT and CPI. Patients received SG 10 mg/kg on days 1 and 8 of 21-day cycles. The primary outcome was centrally reviewed ORR; secondary outcomes were progression-free survival, OS, duration of response, and safety.
RESULTS Cohort 1 included 113 patients (78% men; median age, 66 years; 66.4% visceral metastases; median of three [range, 1-8] prior therapies). At a median follow-up of 9.1 months, the ORR was 27% (31 of 113; 95% CI, 19.5 to 36.6); 77% had a decrease in measurable disease. Median duration of response was 7.2 months (95% CI, 4.7 to 8.6 months), with median progression-free survival and OS of 5.4 months (95% CI, 3.5 to 7.2 months) and 10.9 months (95% CI, 9.0 to 13.8 months), respectively. Key grade $ 3 treatment-related adverse events included neutropenia (35%), leukopenia (18%), anemia (14%), diarrhea (10%), and febrile neutropenia (10%), with 6% discontinuing treatment because of treatment-related adverse events.
CONCLUSION SG is an active drug with a manageable safety profile with most common toxicities of neutropenia and diarrhea. SG has notable efficacy compared with historical controls in pretreatedmUC that has progressed on both prior PLT regimens and CPI. The results from this study supported accelerated approval of SG in this population.
Authors:
Scott T. Tagawa, MD, MS1; Arjun V. Balar, MD2; Daniel P. Petrylak, MD3; Arash Rezazadeh Kalebasty, MD4; Yohann Loriot, MD, PhD5; Aude Fl´echon, MD, PhD6; Rohit K. Jain, MD7; Neeraj Agarwal, MD8; Manojkumar Bupathi, MD, MS9; Philippe Barthelemy, MD, PhD10; Philippe Beuzeboc, MD, PhD11; Phillip Palmbos, MD, PhD12; Christos E. Kyriakopoulos, MD13; Damien Pouessel, MD, PhD14; Cora N. Sternberg, MD1; Quan Hong, MD15; Trishna Goswami, MD15; Loretta M. Itri, MD15; and Petros Grivas, MD, PhD16
1. Weill Cornell Medicine, New York, NY.
2. Perlmutter Cancer Center at NYU Langone Health, New York, NY.
3. Smilow Cancer Center, Yale School of Medicine, New Haven, CT.
4. Norton Cancer Institute, Louisville, KY.
5. Institut de Cancérologie Gustave Roussy, Villejuif, France.
6. Centre Léon Bérard, Lyon, France.
7. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
8. Huntsman Cancer Hospital, Salt Lake City, UT.
9. Rocky Mountain Cancer Centers, Littleton, CO.
10. Hôpitaux Universitaires de Strasbourg/Institut de Cancérologie Strasbourg Europe, Strasbourg, France.
11. Hôpital Foch, Suresnes, France.
12. University of Michigan Comprehensive Cancer Center, Ann Arbor, MI.
13. University of Wisconsin Carbone Cancer Center, Madison, WI.
14. Institut Claudius Regaud/Cancer Comprehensive Center, IUCT, Toulouse, France.
15. Immunomedics, a subsidiary of Gilead Sciences, Inc, Morris Plains, NJ.
16. Fred Hutchinson Cancer Research Center, University of Washington, Seattle Cancer Care Alliance, Seattle, WA.
Citation: Tagawa S., Balar A., Petrylak D., et al., TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors. J Clin Oncol. 2021 Apr 30 [Online ahead of print]
Related Content: ESMO Virtual Congress 2020: TROPHY-U-01 Cohort 1 Final Results: A Phase 2 Study of Sacituzumab Govitecan (SG) in Metastatic Urothelial Cancer That Has Progressed After Platinum and Checkpoint Inhibitors
ESMO 2020: The TROPHY-U-01 Study- Sacituzumab Govitecan for Advanced Urothelial Carcinoma - Petros Grivas