Sacituzumab Govitecan Advised as Potential Combination Therapy With Pembrolizumab in mUC

Sacituzumab govitecan (SG), an antibody-drug conjugate approved by the U.S. FDA in 2020, has been advised to be studied further as a potential addition to be added to standard-of-care checkpoint inhibitor (CPI) pembrolizumab as a combination therapy for patients with metastatic urothelial cancer who have progressed after platinum-based regimens.

“SG in combination with Pembro demonstrated encouraging ORR and CBR, with an overall manageable safety profile with no new safety signal in CPI-naive pts who progressed after prior PLT-based chemotherapy,” reported lead author Petros Grivas, MD, PhD, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, and colleagues who presented interim efficacy and safety results.

CPIs like pembro are standard second-line therapy for MUC patients, with addition to offering limited long-term disease control. In TROPHY-U-01, a multicohort, open-label, global study which included the registrational phase 2 trial for SG monotherapy, the antibody-drug conjugate demonstrated significant activity and manageable safety in such patients, according to the abstract.

Therefore, the researchers presented data from TROPHY-U-01’s Cohort 3, in which 41 patients received the recommended Phase 2 dose of SG (10 mg per kg).

With a median follow-up of 5.8 months, the investigator-assessed overall response rate was 34% (95% CI, 20.1–50.6; 1 CR; 13 PR); the CBR (comprising complete response, partial response, and stable disease) was 44% (95% CI, 28.5–60.3); and PFS was 47%. The media time to response was 2 months (95% CI, 1.3–2.8).  

Treatment-related adverse events of grade 3 or higher occurred in 59% of patients; however, no treatment-related death occurred, according to the investigators. 

"Limitations of the study included a small sample size, a short follow-up period, and the lack of randomization," the authors concluded.

Source:

Grivas P, Pouessel D, Park C, et al. TROPHY-U-01 Cohort 3: Sacituzumab govitecan (SG) in combination with pembrolizumab (Pembro) in patients (pts) with metastatic urothelial cancer (mUC) who progressed after platinum (PLT)-based regimens. Abstract presented at: ASCO Genitourinary Cancers Symposium; Feb. 17-19, 2022; San Francisco, CA. Abstract 434