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Purpose

Patients with advanced endometrial cancer (EC) who progress on or after platinum-based therapy and immunotherapy have a poor prognosis. We report efficacy and safety of sacituzumab govitecan (SG), a trophoblast cell-surface antigen 2 (Trop-2)–directed antibody-drug conjugate, in patients with advanced EC.

Methods

TROPiCS-03 (ClinicalTrials.gov identifier: ) is a multicohort, open-label, phase II basket study in patients with metastatic solid tumors. Eligible patients in the EC cohort received SG 10 mg/kg once on days 1 and 8 every 3 weeks. The primary end point was objective response rate (ORR) by investigator's assessment per RECIST v1.1. Secondary end points included clinical benefit rate (CBR; complete and partial response, and stable disease ≥6 months), duration of response (DOR), and progression-free survival (PFS) per investigator assessment, overall survival, and safety. Trop-2 expression of archival or baseline tumor specimens was analyzed by immunohistochemistry.

Results

At data extraction date, 41 patients were enrolled. Median follow-up was 5.8 months (range 0.7-19.3); median previous therapies was 3 (range 1-6); and 85% of patients received previous chemotherapy and immunotherapy. ORR was 22% (95% CI 11-38); CBR was 32% (95% CI 18-48). Median DOR was 8.8 months (95% CI 2.8 to not estimable); median PFS was 4.8 months (95% CI 2.8-9.8). Trop-2 exploratory analysis was conducted retrospectively for 39 patients. Tumor Trop-2 protein was highly expressed in EC, showing limited correlation with efficacy. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 73% of patients. Study drug discontinuation due to TRAEs was 5%. Two deaths occurred, deemed unrelated to SG.

Conclusion

Findings from TROPiCS-03 showed encouraging efficacy of SG with a manageable toxicity profile in a heavily pretreated population with advanced EC. Safety findings were consistent with the known SG safety profile.

Read an interview about the study here and expert commentary about it here.