Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3

Abstract

Purpose: Pembrolizumab is standard therapy for patients with metastatic urothelial cancer (mUC) who progress after first-line platinum-based chemotherapy; however, only approximately 21% of patients respond. Sacituzumab govitecan (SG) is a trophoblast cell surface antigen-2-directed antibody-drug conjugate with US Food and Drug Administration-accelerated approval to treat patients with locally advanced or mUC who previously received platinum-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report the primary analysis of TROPHY-U-01 cohort 3.

Methods: TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label phase II study. Patients were CPI-naïve and had mUC progression after platinum-based chemotherapy in the metastatic setting or ≤12 months in the (neo)adjuvant setting. Patients received 10 mg/kg of SG once on days 1 and 8 and 200 mg of pembrolizumab once on day 1 of 21-day cycles. The primary end point was objective response rate (ORR) per central review. Secondary end points included clinical benefit rate (CBR), duration of response (DOR) and progression-free survival (PFS) per central review, and safety.

Results: Cohort 3 included 41 patients (median age 67 years; 83% male; 78% visceral metastases [29% liver]). With a median follow-up of 14.8 months, the ORR was 41% (95% CI, 26.3 to 57.9; 20% complete response rate), CBR was 46% (95% CI, 30.7 to 62.6), median DOR was 11.1 months (95% CI, 4.8 to not estimable [NE]), and median PFS was 5.3 months (95% CI, 3.4 to 10.2). The median overall survival was 12.7 months (range, 10.7-NE). Grade ≥3 treatment-related adverse events occurred in 61% of patients; most common were neutropenia (37%), leukopenia (20%), and diarrhea (20%).

Conclusion: SG plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with mUC who progressed after platinum-based chemotherapy. No new safety signals were detected. These data support further evaluation of SG plus CPI in mUC.

FIG 1.

Flow diagram. CPI, checkpoint inhibitor; IV, intravenous; mUC, metastatic urothelial cancer.

FIG 2.

Kaplan-Meier analysis of (A) DOR, (B) PFS, and (C) OS. DOR, duration of response; NE, not estimable; OS, overall survival; PFS, progression-free survival.

FIG 3.

Tumor responses per central review. (A) Waterfall plot showing best percentage change from baseline in the sum of the diameters of the target lesions in 39 patients (excludes two patients who were missing percentage change from baseline). The dashed line indicates threshold for partial response, according to RECIST v1.1. Target lesions were reduced in 72% of patients (28 of 38) with at least one postbaseline target lesion measurement. (B) Spider plot of tumor response by week. (C) Swimmer plot of response and duration. ^aPatients who achieved a complete response without a 100% reduction relative to the assessment at baseline had a lymph node as the target lesion. PD, progressive disease.

FIG A1.

ORR in key prespecified subgroups per central review: forest plot showing ORR in different subgroups. Horizontal line represents CI. ^aAll patients had two or fewer therapies and two or fewer chemotherapies. ECOG PS, Eastern Cooperative Oncology Group performance status; NA, not available; ORR, objective response rate.