378MO - Efficacy and safety of disitamab vedotin in treatment of HER2 expressed advanced or recurrent gynecological cancers

Background

Disitamab vedotin (RC48) is a human epidermal growth factor 2 (HER2)–directed antibody-drug conjugate, with a novel humanized anti-HER2 antibody disitamab conjugated to monomethyl auristatin E (MMAE) via a cleavable linker. RC48 has been approved for the treatment of HER2-positive gastric cancer and urothelial carcinoma patients in China. However, anti-HER2 treatments in gynecological tumors with HER2 expression are still limited.

Methods

This study retrospectively analyzed the efficacy and safety of RC48 monotherapy or combination treatments in HER2-expressing advanced or recurrent gynecological tumors. The primary endpoint was objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety.

Results

This study enrolled 27 advanced or recurrent gynecological tumor patients, including 18 ovarian cancer patients, 7 cervical cancer patients, and 2 endometrial cancer patients. One, 11 and 14 of the 27 patients was defined as HER2 3+, 2+, and 1+ by IHC, respectively. Among the 27 patients, 22 were evaluable with enough information. The ORR and DCR were 54.5% and 72.7% respectively, with 4 patients achieving complete response (CR), 8 patients achieving partial response (PR), and 4 patients achieving stable disease (SD). The ORR for ovarian cancer, cervical cancer and endometrial cancer were 42.9%, 83.3% and 50%, respectively. The ORR among patients with HER2 1+ and 2+ were 50% and 60%, respectively. The median PFS (mPFS) for the overall population was 6.60 months (95% CI: 4.63-NR), with 4.17 months (95% CI: 3.70-NR) for ovarian cancer patients, 9.73 (95% CI: 7.83-NR) months for cervical cancer patients, and 6.27 months (95% CI: 5.93-NR) for endometrial cancer patients. The mPFS were 4.80 months (95% CI: 3.97-NR) and 6.60 months (95% CI: 4.63-NR) among patients with HER2 2+ and 1+ respectively. The most common adverse events were decreased white blood cell count (36.4%) and decreased neutrophil count (36.4%), with rare occurrence of grade 4 or higher adverse events.

Conclusions

This study indicates that RC48 has promising efficacy and manageable safety for advanced or recurrent gynecological tumors expressing HER2.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Guangzhou Major Clinical Projects(2023P-ZD12); Guangdong Basic and Applied Basic Research Foundation (2024A1515013004, 2023A1515012647, 2021A1515220142).

Disclosure

All authors have declared no conflicts of interest.