A Phase II Evaluation of the Efficacy and Safety of Sacituzumab Govitecan in Patients with Recurrent Uterine Cancer.

PURPOSE: Patients with endometrial cancer who progress after chemotherapy/immunotherapy have limited treatment options. We evaluated the activity and safety of sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, in patients with advanced/recurrent endometrial cancer, including carcinosarcoma.

PATIENTS AND

METHODS

This was a phase II, two-stage, open-label, investigator-initiated trial of patients with persistent/recurrent endometrial cancer who had progressed following ≥1 prior chemotherapy. Patients received SG 10 mg/kg on days 1 and 8 every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST v1.1. Secondary endpoints included clinical benefit rate [CBR = complete response (CR) + partial response (PR) + stable disease ≥ 6 months], duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Trop-2 expression was analyzed by immunohistochemistry as an H-score.

RESULTS

Fifty patients were screened, and 21 enrolled during stage 1; 34 patients were screened, and 29 enrolled during stage 2; 84% (n = 42) of the patients harbored serous carcinoma, carcinosarcoma, or grade 3 endometrioid tumors. Patients received a median of two prior therapies (range, 1-4) and 50% had failed pembrolizumab/dostarlimab. At a median follow-up (range) of 11 (2.9-65.5) months, the ORR was 28% [95% confidence interval (CI), 16%-42%], including CRs (4%) and PRs (24%). The median DOR (95% CI) was 9.3 (2-12.9) months, with four still responding. The CBR was 52% (26/50). The median PFS and OS were 5.5 (95% CI, 3.7-7.4) and 17.5 (95% CI, 10.4-22.2) months, respectively. Grade 3 to 4 toxicity occurred in 88% with no attributable deaths. Mean H-scores did not predict response.

CONCLUSIONS

SG demonstrated encouraging efficacy in a pretreated population that included biologically aggressive recurrent endometrial cancer. Adverse events were consistent with the known safety profile.