Multinational phase 2 trial of second-line sacituzumab govitecan plus pembrolizumab for CPI-naïve metastatic urothelial carcinoma

Pembrolizumab is the standard therapy for patients with metastatic urothelial cancer (mUC) who progress after first-line platinum-based chemotherapy; however, only approximately 20% of patients respond. Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate. Cohort 3 of the multinational phase 2 TROPHY-U-01 trial evaluated the combination of SG and pembrolizumab for checkpoint inhibitor-naïve patients with mUC progressing after platinum-based chemotherapy. With a median follow-up of 14.8 months, objective response rate and clinical benefit rate were 41% (95% CI 26.3-57.9) and 46% (95% CI 30.7-62.6), respectively. The median DOR, PFS, and OS were 11.1 months (95% CI 4.8-NE), 5.3 months (95% CI 3.4-10.2), and 12.7 months (range 10.7-NE), respectively. Grade ≥3 treatment-related adverse events occurred in 68% of patients. The authors conclude that SG plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with mUC who progressed after platinum-based chemotherapy.