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

Daniel P. Petrylak, Scott T. Tagawa, Rohit K. Jain, Manojkumar Bupathi, Arjun Balar, Arash Rezazadeh Kalebasty, Saby George, Phillip Palmbos, Luke Nordquist, Nancy Davis, Chethan Ramamurthy, Cora N. Sternberg, Yohann Loriot, Neeraj Agarwal, Chandler Park, Julia Tonelli, Morganna Vance, Huafeng Zhou, Petros Grivas, Daniel P. PetrylakScott T. Tagawa, Rohit K. Jain, Manojkumar Bupathi, Arjun Balar, Arash Rezazadeh Kalebasty, Saby George, Phillip Palmbos, Luke Nordquist, Nancy Davis, Chethan Ramamurthy, Cora N. Sternberg, Neeraj Agarwal, Chandler Park, Julia Tonelli, Morganna Vance, Huafeng Zhou, Petros Grivas, Yohann Loriot

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

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    Résumé

    PURPOSESacituzumab 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.METHODSTROPHY-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.RESULTSCohort 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%).CONCLUSIONSG 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.

    langue originaleAnglais
    Pages (de - à)3410-3420
    Nombre de pages11
    journalJournal of Clinical Oncology
    Volume42
    Numéro de publication29
    Les DOIs
    étatPublié - 10 oct. 2024

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