Efficacy and Safety of Sacituzumab Govitecan in Patients With Advanced Solid Tumors (TROPiCS-03): Analysis in Patients With Advanced Endometrial Cancer

Abstract

Purpose: Patients with advanced endometrial cancer (EC) who progress on or after platinum-based therapy and immunotherapy have 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: NCT03964727) 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. 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 three (range, 1-6); and 85% of patients received previous chemotherapy and immunotherapy. ORR was 22% (95% CI, 11 to 38); CBR was 32% (95% CI, 18 to 48). Median DOR was 8.8 months (95% CI, 2.8 to not estimable); median PFS was 4.8 months (95% CI, 2.8 to 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.

FIG 1.

(A) Best percentage change from baseline in total sum of target lesion diameters and (B) spider plot of tumor response over time. NE, not estimable; PD, progressive disease; PR, partial response; SD, stable disease.

FIG 2.

Kaplan-Meier plot of PFS per investigator assessment. PFS, progression-free survival; SG, sacituzumab govitecan.

FIG 3.

Analysis of efficacy by Trop-2 expression: (A) Kaplan-Meier estimates of PFS by H-score median, (B) best percent tumor volume change from baseline by Trop-2 H-score, and (C) best overall response by Trop-2 H-score. (B) Best overall response calculated for 33 patients as patients without tumor change data were excluded. (C) Trop-2 data were only available for eight of nine patients with PR and 17 of 18 patients with SD. HR, hazard ratio; NE, not estimable; PFS, progression-free survival; PR, partial response; SD, stable disease; Trop-2, trophoblast cell-surface antigen 2.

FIG A1.

Kaplan-Meier plot of duration of response per investigator assessment. NE, not estimable.

FIG A2.

Trop-2 expression distribution. Calculated for 39 patients. Trop-2, trophoblast cell surface antigen 2.