The addition of sacituzumab govitecan (Trodelvy), an antibody–drug conjugate, to the PD-1 inhibitor pembrolizumab (Keytruda) showed encouraging antitumor activity in checkpoint inhibitor–naïve patients with metastatic urothelial cancer, according to an analysis of the results of cohort 3 from the phase 2 TROPHY-U-01 clinical trial, which were presented at the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium by Petros Grivas, MD, PhD, Clinical Director, Genitourinary Cancers Program, University of Washington School of Medicine, Seattle; and Associate Professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle.
Better treatment options are needed for metastatic urothelial cancer because patients’ outcomes remain poor. The investigators hypothesized that sacituzumab govitecan plus pembrolizumab would improve current approaches to treatment.
Cohort 3 of the open-label, multicohort phase 2 TROPHY-U-01 study was designed to enroll up to 61 patients whose disease progressed after platinum-based therapy and who had not received checkpoint inhibitor therapy. The patients received sacituzumab govitecan 10 mg/kg on days 1 and 8 every 21 days and 200 mg of pembrolizumab on day 1 every 21 days. Treatment continued until disease progression or unacceptable adverse events (AEs).
The primary end point was the objective response rate (ORR); key secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
In all, 83% of the patients were male, and the median age was 67 years, and 61% had an Eastern Cooperative Oncology Group performance score of 1. Among the patients, 49% and 27% had Bellmunt risk factor scores of 1 and 2, respectively. A total of 49% of the patients received adjuvant or neoadjuvant chemotherapy. The best response to previous systemic therapy in the metastatic setting was a complete response (CR) in 1 patient and a partial response (PR) in 2 patients.
At a median follow-up of 5.8 months, treatment with the sacituzumab govitecan plus pembrolizumab combination had an ORR of 34%, including 1 CR, 13 PRs, and 11 patients having stable disease (SD). Among the patients with SD, 4 had SD for ≥6 months.
The ORR plus SD rate was 61%. The median time to response was 2 months, and the median DOR was not reached. The median PFS was 5.5 months, and the median OS was not reached.
An ORR was observed in subgroups of patients with or without baseline visceral metastases and liver involvement (41.7% and 31%, respectively). The ORRs for the patients with Bellmunt risk factor scores of 0, 1, and 2 were 40%, 35%, and 27.3%, respectively.
“These data support further evaluation of antibody–drug conjugate/checkpoint inhibitor combination [therapy] in metastatic urothelial cancer in the platinum-refractory setting, and probably in earlier lines of therapy in a different patient population,” stated Dr Grivas. “Additional follow up for survival events and biomarkers are ongoing.”
In cohort 3, AEs of any grade included diarrhea (76%), nausea (59%), and anemia (56%), with grade ≥3 AEs of neutropenia (27%), diarrhea (24%), anemia (20%), and leukopenia (20%).
The median duration of treatment was 4 months with sacituzumab govitecan and 3.5 months with pembrolizumab. In all, 68% of patients permanently discontinued treatment, and 32% were still receiving treatment at the time of data cutoff. The reasons for treatment discontinuation included progressive disease (51%), withdrawal of consent (5%), and AEs (3%). Grade 3 or 4 treatment-related AEs were reported in 59% of patients; 39% of patients required dose reduction of sacituzumab govitecan due to treatment-related AEs.
Other TROPHY-U-01 cohorts continue to be evaluated.