Sacituzumab Govitecan Plus Pembrolizumab Shows Promise in Platinum-Refractory/Relapsed Metastatic Urothelial Carcinoma

Primary Analysis of Cohort 3 From Phase 3 TROPHY-U-01

According to a primary analysis of the phase 2 TROPHY-U-01 trial, sacituzumab govitecan plus pembrolizumab demonstrated a high rate of response with a manageable toxicity profile among patients with metastatic urothelial carcinoma who had progressed following platinum-based chemotherapy.

The standard therapy for patients with metastatic urothelial cancer who progress after platinum-based chemotherapy in the first-line setting is pembrolizumab. “However,” Petros Grivas, MD, Fred Hutchinson Cancer Center at University of Washington, Seattle, and coauthors, wrote, “only approximately 21% of patients respond,” and so “new treatment strategies are urgently needed in this setting.”

The multicohort, open-label phase 2 TROPHY-U-01 trial enrolled patients with metastatic urothelial cancer who had not yet been treated with checkpoint inhibitors and had progressed after platinum-based chemotherapy in the metastatic setting or within the 12 months following neo/adjuvant treatment. In cohort 3, 41 patients received 10 mg/kg of sacituzumab govitecan once on days 1 and 8, plus 200mg of pembrolizumab once on day 1 of 21-day cycle. The primary end point was objective response rate (ORR). Secondary end points included clinical benefit rate, duration of response (DOR), progression-free survival (PFS) per central review, and safety.

It was previously reported that sacituzumab govitecan monotherapy demonstrated a ORR of 27% with a median DOR of 7.2 months and a median OS of 10.9 months among the heavily pretreated population in Cohort 1 of this trial.

With a median follow-up duration of 14.8 months, the ORR of Cohort 3 was 41% with 20% achieving a complete response, and the clinical benefit rate was 46%. The median DOR was 11.1 months and the median PFS was 5.3 months. There was a median overall survival of 12.7 months. Grade ≥3 treatment-related adverse events were reported in 61% of patients and the most common were neutropenia (37%), leukopenia (20%), diarrhea (20%), and anemia (17%). Treatment-related adverse events led to sacituzumab govitecan interruptions in 46%, dose reductions in 39% of patients, and discontinuations in 15% of patients.

Dr Grivas et al concluded sacituzumab govitecan plus pembrolizumab “demonstrate[ed] higher ORR compared with historical pembrolizumab monotherapy data in this setting, with a promising survival signal.”

Associate editor for the Journal of Clinical Oncology, Michael A Carducci, MD, Johns Hopkins Medicine, Baltimore, Maryland, added that the combination of sacituzumab govitecan plus pembrolizumab “is a novel regimen moving forward in a number of clinical trials, along with other [antibody drug conjugates] and immune checkpoint inhibitor combinations for urothelial cancer. This study provides a summary of early clinical activity and the rationale for future study.”

Source:

Grivas P, Pouessel D, Park CH, et al. Sacituzumab govitecan in combination with pembrolizumab for patients with metastatic urothelial cancer that progressed after platinum-based chemotherapy: TROPHY-U-01 cohort. J Clin Oncol. Published on January 23, 2024. doi:10.1200/JCO.22.02835