Sacituzumab Govitecan Shows Antitumor Activity in Metastatic Cervical Cancer

Updated results from the phase 2 EVER-132-003 trial (NCT05119907) demonstrated promising antitumor activity of sacituzumab govitecan (Trodelvy) in Chinese patients with recurrent or metastatic cervical cancer, as presented at the European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Asia Congress 2025. The study evaluated heavily pretreated patients, including a subgroup with prior immunotherapy exposure.^1,2

In the full analysis set (FAS; n = 40), the objective response rate (ORR) was 43.0% (95% CI, 27.0%-59.0%), with a disease control rate (DCR) of 85.0% (95% CI, 70.0%-94.0%) and a median duration of response (DOR) of 9.2 months (95% CI, 4.6-11.7).

Responses included 1 complete response (3%) and 16 partial responses (40%). A similar benefit was observed in the postimmunotherapy subgroup (post-IO; n = 27), with an ORR of 48% and DCR of 89%.

In the FAS cohort, the median progression-free survival (PFS) was 7.1 months (95% CI, 4.2-8.4), the 6-month PFS rate was 51.0% (95% CI, 35.0%-66.0%), and the 12-month PFS rate was 20.0% (95% CI, 8.0%-36.0%).

In the post-IO cohort, the median PFS was 8.3 months (95% CI, 4.2-11.8), the 6-month PFS rate was 62.0% (95% CI, 41.0%-78.0%), and the 12-month PFS rate was 27.0% (95% CI, 11.0%-47.0%). The median overall survival (OS) was 16.5 months (95% CI, 13.4-not evaluable [NE]) in the FAS cohort and 17.2 months (95% CI, 13.4-NE) in the post-IO cohort.

In the FAS cohort, the 12-month OS rate was 71.0% (95% CI, 54.0%-83.0%) and the 24-month OS rate was 38.0% (95% CI, 19.0%-57.0%). In the post-IO cohort, the 12-month OS rate was 79.0% (95% CI, 57.0%-91.0%) and the 24-month OS rate was 37.0% (95% CI, 15.0%-60.0%).

In the FAS cohort, 1 patient (3%) had a confirmed complete response (CR), 16 patients (40%) had a confirmed partial response, 17 patients (43%) had stable disease, and 5 patients (13%) had progressive disease. One patient was not evaluable. In the post-IO cohort, the responses were 4%, 44%, 48%, 0%, and 4%, respectively.

“Overall, 83% [n = 33] of all treated patients had a reduction in target lesions,” Jusheng An, PhD, Department of Gynecologic Oncology, National Cancer Center, Beijing, China, said in a presentation of the data.

The trial evaluated patients who were refractory or intolerant to platinum- and taxane-based chemotherapy, with no prior treatment with TROP-2 inhibitors and an ECOG performance status of 0 or 1.

Sacituzumab govitecan is made up of a humanized antitrophoblast cell-surface antigen 2 monoclonal antibody coupled to SN-38, the active metabolite of the topoisomerase inhibitor irinotecan, via a proprietary hydrolyzable linker.³

Patients received 10 mg/kg of sacituzumab govitecan on days 1 and 8, every 21 days until disease progression or toxicity. The primary end point was ORR, and secondary end points were DCR, DOR, PFS, OS, and safety. At the October 2, 2024, data cutoff, the median follow-up was 9.6 months (range, 1.4-30.9).

Patient Characteristics

The median age in both cohorts was 54 years (FAS: range, 31-71; post-IO: range, 33-71). The majority of patients in the FAS cohort were ECOG performance status 1 (60%) but in the post-IO cohort, the majority of patients were ECOG performance status 0 (56%).

In both cohorts, the majority of patients had squamous cell carcinoma. Specifically, in the FAS cohort, 85% of patients had this histology type and in the post-IO cohort, 89% had squamous cell carcinoma.

Patients were heavily pretreated in both cohorts, with 43% of patients in the FAS cohort receiving a median of 2 prior regimens compared with 56% in the post-IO cohort. Fifteen percent and 19%, respectively, were treated with a median of 3 or more prior regimens.

Safety

In the FAS cohort, all patients reported treatment-emergent adverse events (TEAEs) and all were treatment-related (TRAEs).

Sixty-three percent of patients reported grade 3 or higher TEAEs, all of which were TRAEs. TEAEs leading to dose interruption and dose reduction were 73% and 20%, respectively.

The most frequently reported grade 3 or higher TEAEs were neutropenia (43%), leukopenia (38%), and anemia (20%). Febrile neutropenia was reported in 8% of patients. No deaths related to TEAEs were reported.

The safety profile was consistent with the known safety profile of sacituzumab govitecan, and findings support the potential role of the agent in recurrent/metastatic cervical cancer, particularly in pretreated patients, including those with prior immunotherapy exposure. Further investigation is warranted to confirm these results.

REFERENCES:

1. An J, Li G, Zhang Y, et al. Sacituzumab govitecan for Chinese patients with recurrent/metastatic cervical cancer: results from the EVER-132-003 basket study. Presented at: ESMO Targeted Anticancer Therapies Asia Congress 2025; July 18-20, 2025; Hong Kong SAR, China. Abstract 2O.

2. An J, Li G, Zhang Y, et al. Sacituzumab govitecan for Chinese patients with recurrent/metastatic cervical cancer: results from the EVER-132-003 basket study. Ann Oncol. 2025;10(suppl 6):1-6. doi:10.1016/esmoop/esmoop105345

3. Goldenberg DM, Cardillo TM, Govindan SV, Rossi EA, Sharkey RM. Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget. 2015;6(26):22496-22512. doi:10.18632/oncotarget.4318