Sacituzumab Govitecan Shows 28% Response Rate in Recurrent Endometrial Cancer

Why This Study Matters

Endometrial cancer is the most common gynecologic malignancy in the United States, with an estimated 69,120 new cases and 13,860 deaths expected in 2025, and incidence is projected to double by 2030. Patients who progress after platinum-based chemotherapy and anti-PD-1 therapy have few effective options: a real-world cohort of nearly 2,000 U.S. patients with advanced or recurrent disease found median overall survival ranging from only 14.1 to 31.8 months after first-line therapy, and just 27% of patients went on to receive a third line of treatment.

Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate already approved for metastatic breast cancer. This single-center, investigator-initiated Phase II trial evaluated SG in a heavily pretreated population of patients with persistent or recurrent endometrial cancer, including biologically aggressive histologic subtypes — serous carcinoma, carcinosarcoma, and grade 3 endometrioid tumors — that made up 84% of the enrolled cohort and are frequently excluded from other trial designs.

Study Design

This was a single-center, open-label, Phase II, two-stage (Simon optimal two-stage design) investigator-initiated trial. Enrollment ran from March 2020 to December 2024. Patients received SG at 10 mg/kg intravenously on days 1 and 8 of a 21-day cycle until progression, unacceptable toxicity, withdrawal, or death. Stage 1 enrolled 21 evaluable patients selected for Trop-2 expression (2+ or greater staining in 50% of tumor cells); stage 2 enrolled 29 additional patients without prospective Trop-2 testing, after more than 90% of stage 1 tumors were found to express Trop-2. The primary endpoint was objective response rate (ORR) by RECIST v1.1; secondary endpoints included clinical benefit rate, duration of response, progression-free survival, overall survival, and safety.

Patient Population

Patients had histologically documented advanced or metastatic endometrial cancer that progressed after at least one prior platinum-based chemotherapy regimen, with no cap on prior lines of therapy. Median age was 68 years (range, 30-82). All patients had received prior carboplatin/paclitaxel; 50% had received pembrolizumab or dostarlimab, and 26% had received doxorubicin. By histology: 48% serous (mixed or pure) carcinoma, 22% carcinosarcoma, 22% endometrioid (73% of which were grade 3), and 8% other histologies. Mismatch repair status was available in 46 patients, of whom only 4.3% were MMR-deficient. Median follow-up was 11 months (range, 2.9-65.5 months).

Primary Endpoint Results

The authors note this ORR compares favorably with historic response rates for single-agent chemotherapies cited in the article's discussion — including paclitaxel (27.3%), docetaxel (7.7%), ixabepilone (12%), liposomal doxorubicin (9.5%), and oxaliplatin (13.5%) — and is consistent with the Phase II TROPiCS-03 endometrial cohort (ORR 22%) and the Phase I/II IMMU-132-01 basket trial (ORR 22%, OS 11.9 months). These comparisons are drawn from separate prior studies discussed within this article's own text, not from an independent within-trial comparator arm.

Subgroup Analyses

Objective responses were not confined to any particular histologic subtype (Fisher's exact test, P = 0.32):

An exploratory analysis of 43 evaluable patients examined response by Trop-2 membrane H-score, split at the median value of 240:

Progression-free survival by H-score was 3.8 months (95% CI, 3.4-11.3) at or above the median versus 5.6 months (95% CI, 3.5-9.2) below the median (HR 0.93; 95% CI, 0.47-1.81; P = 0.83). Mean membrane H-score did not significantly differ between responders (244.8 ± 49.9) and nonresponders (198.4 ± 80.5; P = 0.072). ORR by enrollment stage was 33% in stage 1 versus 25% in stage 2. Efficacy did not appear to depend on Trop-2 expression level in this exploratory analysis.

Safety Profile

Grade 3-4 treatment-emergent adverse events occurred in 44 of 50 patients (88%), reported 323 times in total. Serious adverse events occurred in 25 patients (50%). Three patients discontinued treatment due to grade 3-4 adverse events (myocardial infarction, cerebral edema, and pleural effusion with hypoxia and dyspnea, one each). Treatment delays were required in 27 patients and dose reductions in 9 patients. No treatment-related deaths were reported.

The article states toxicities were aligned with the known safety profile for the drug in other solid tumors, and were managed with growth factor support, antimotility agents, and standard supportive care. The authors note the side-effect profile mirrors the Phase III ASCENT trial of SG in metastatic triple-negative breast cancer, which reported higher rates of grade 3 or higher neutropenia (51%), diarrhea (10%), leukopenia (10%), anemia (8%), and febrile neutropenia (6%).

SG demonstrated encouraging efficacy in a pretreated population that included biologically aggressive recurrent endometrial cancer. Adverse events were consistent with the known safety profile.
— Santin et al., Discussion, Clinical Cancer Research (2026)

Interpretation and Broader Context

The study met its primary efficacy endpoint in a population enriched for biologically aggressive, difficult-to-treat histologies with no limit on prior treatment. Response did not appear to require high Trop-2 expression, a finding the authors say is consistent with mechanisms such as bystander cytotoxic effect, high drug-to-antibody ratio, and extracellular linker cleavage that allow antibody-drug conjugates to act even in tumors with lower target expression. The authors note this is a single-arm study without a comparator, with a small sample size and incomplete exploratory biomarker data, which limits conclusions about the relationship between Trop-2 expression and either efficacy or toxicity.

An international Phase III trial (ASCENT-GYN-01/GOG-3104/ENGOT-en26/APGOT-EN2) comparing SG to physician's choice chemotherapy in patients who have failed both platinum-based chemotherapy and immune checkpoint inhibition is currently underway, and will be needed to confirm these single-arm findings in a randomized, controlled setting.