TROPHY-U-01 Cohort 3: Sacituzumab govitecan (SG) in combination with pembrolizumab (Pembro) in patients (pts) with metastatic urothelial cancer (mUC) who progressed after platinum (PLT)-based regimens.
Petros Grivas, Damien Pouessel, Chandler H. Park, Philippe Barthélémy, Manojkumar Bupathi, Daniel P. Petrylak, Neeraj Agarwal, Aude Fléchon, Chethan Ramamurthy, Nancy B. Davis, Alejandro Recio‐Boiles, Scott T. Tagawa, Cora N. Sternberg, Astha Bhatia, Cabilia Pichardo, Trishna Goswami, Yohann Loriot
Abstract
434 Background: Checkpoint inhibitors (CPIs) are standard therapy for pts with mUC after PLT-based regimens, with limited long-term disease control. SG is an antibody-drug conjugate composed of an anti-trophoblast cell-surface antigen 2 (Trop-2) antibody coupled to SN-38 (a topoisomerase-I inhibitor) via a proprietary hydrolyzable linker. In the TROPHY-U-01 registrational phase 2 trial, SG monotherapy demonstrated significant activity and manageable safety in pts with mUC who progressed after prior PLT-based chemotherapy and CPI, with 27% objective response rate (ORR) and median overall survival of 11 months (Tagawa, et al. J Clin Oncol. 2021). Here, we present interim efficacy and safety results of combining SG with Pembro as 2nd-line therapy in CPI-naive pts with mUC who progressed after PLT-based chemotherapy (cohort 3). Methods: TROPHY-U-01 is a multicohort, open-label, global phase 2 trial. Eligible pts had measurable disease, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1, and creatinine clearance ≥30 mL/min. The recommended phase 2 dose (RP2D) was determined during a 10-pt safety lead-in, and additional pts were enrolled at the RP2D in a Simon 2-stage design. Primary endpoint: ORR by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Key secondary endpoints: investigator-assessed ORR, clinical benefit rate [CBR; complete response (CR) + partial response (PR) + stable disease], progression-free survival (PFS), and safety. Results: At the time of data cutoff, 41 pts received at least a dose of SG at the RP2D (10 mg/kg). Of these 41 pts, median (range) age was 67y (46–86), 83% men, 61% ECOG PS 1, 76% had ≥1 Bellmunt risk factor, and median (range) number of prior anticancer regimens was 1 (1–3). At a median follow-up of 5.8 mo, the investigator-assessed ORR was 34% (95% CI, 20.1–50.6; 1 CR; 13 PR); CBR was 44% (95% CI, 28.5–60.3); 6-mo PFS rate was 47%. Median time to response was 2.0 mo (95% CI, 1.3–2.8). Most common treatment-emergent adverse events (TEAEs) were diarrhea (76%), nausea (59%), anemia (56%), neutropenia (44%), and asthenia (41%). Treatment-related grade ≥3 AEs occurred in 59% of pts. Key grade ≥3 TEAEs of any cause included diarrhea (24%), anemia (20%), febrile neutropenia (10%), fatigue (7%), and asthenia (5%). Two pts discontinued treatment due to treatment-related AEs. No treatment-related death occurred. Conclusions: SG in combination with Pembro demonstrated encouraging ORR and CBR, with an overall manageable safety profile with no new safety signal in CPI-naive pts who progressed after prior PLT-based chemotherapy. The data support further evaluation of SG plus CPI in mUC. Limitations: small sample size, short follow-up, and lack of randomization. Biomarker evaluation is ongoing. Clinical trial information: NCT03547973.