Dr Grivas on Sacituzumab Govitecan Plus Pembrolizumab in Metastatic Urothelial Cancer

Petros Grivas, MD, PhD, professor, Clinical Research Division, Fred Hutch Cancer Center, clinical director, Genitourinary Cancers Program, University of Washington Medicine, professor, Department of Medicine, Division of Oncology, University of Washington School of Medicine, discusses findings from the primary analysis of cohort 3 of the phase 2 TROPHY U-01 trial (NCT03547973) in patients with metastatic urothelial cancer.

Cohort 3 of TROPHY U-01 consisted of adult patients with metastatic urothelial cancer who had progressed following treatment with platinum-based chemotherapy in the metastatic setting or within 12 months of completing platinum-based chemotherapy in the neoadjuvant or adjuvant setting and were naïve to checkpoint inhibitors. Patients in this single-arm cohort received sacituzumab govitecan-hziy (Trodelvy) at 10 mg/kg on days 1 and 8 plus pembrolizumab (Keytruda) at 200 mg on day 1 of each 21-day cycle. The primary end point of this cohort was overall response rate (ORR), with a target ORR of 41%.

In cohort 3, the ORR with sacituzumab govitecan and pembrolizumab was 41%, meeting the cohort’s primary end point, Grivas says. Of the responders, 8 achieved a complete response (CR), translating to a 20% CR rate, and the clinical benefit rate was 46%. Responses were seen across prespecified patient subsets, including those with liver metastases, those with visceral metastases, and those with 2 Bellmunt risk factors, Grivas explains. In addition, 72% of the evaluable patients experienced tumor reduction.

The median duration of response was 11.1 months, which further supports the hypothesis that adding pembrolizumab to sacituzumab govitecan results in deep and durable responses, Grivas emphasizes. The median progression-free survival (PFS) in cohort 3 was 5.32 months and the median overall survival (OS) was 12.75 months. Although TROPHY U-01 is a single-arm phase 2 trial with patient selection bias that warrants caution when considering these PFS and OS data, these efficacy signals are promising, Grivas concludes.