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
| Autor: | Scott T. Tagawa, Yohann Loriot, Daniel P. Petrylak, Loretta M. Itri, Arjun Vasant Balar, Trishna Goswami, Aude Flechon, Quan Hong, Manojkumar Bupathi, Arash Rezazadeh Kalebasty, Rohit Jain, Petros Grivas, Christos Kyriakopoulos, Philippe Barthélémy, Philippe Beuzeboc, Phillip L. Palmbos, Cora N. Sternberg, Neeraj Agarwal, Damien Pouessel |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research Urologic Neoplasms Metastatic Urothelial Carcinoma Immunoconjugates Organoplatinum Compounds medicine.medical_treatment Immune checkpoint inhibitors Antibodies Monoclonal Humanized Cohort Studies 03 medical and health sciences 0302 clinical medicine Open label study Antineoplastic Combined Chemotherapy Protocols medicine Humans In patient Immune Checkpoint Inhibitors Aged Aged 80 and over Chemotherapy business.industry Combination chemotherapy Middle Aged 030104 developmental biology Oncology 030220 oncology & carcinogenesis Sacituzumab govitecan Cancer research Camptothecin Female business |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 39(22) |
| ISSN: | 1527-7755 0354-7973 |
| Popis: | PURPOSE Patients with metastatic urothelial carcinoma (mUC) who progress on platinum-based combination chemotherapy (PLT) and checkpoint inhibitors (CPIs) have limited options that offer objective response rates (ORRs) of approximately 10% with a median overall survival (OS) of 7-8 months. Sacituzumab govitecan (SG) is a TROP-2–directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC. 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 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 pretreated mUC that has progressed on both prior PLT regimens and CPI. The results from this study supported accelerated approval of SG in this population. |
| Databáze: | OpenAIRE |
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