Evaluation of the effectiveness and safety of disitamab vedotin for HER2-expressing advanced or recurrent gynecological cancers.

Abstract

e17512 Background: Recent evolution of treatment landscape in advanced or recurrent gynecological cancers has led to novel treatments such as antibody-drug conjugate (ADC) directed to HER2. Disitamab Vedotin (DV, RC48) is a novel HER2-targeted ADC coupling of disitamab with monomethyl auristatin E via a cleavable linker. The RC48-C018 trial showed promising anti-tumor activity and an acceptable safety profile associated with RC48 monotherapy in patients with HER2 expressing (IHC 1+, 2+,3+) recurrent or metastatic cervical cancer. Here, we retrospectively analyzed the efficacy and safety of RC48 monotherapy or combination treatments in HER2-expressing advanced or recurrent gynecological cancers in a real-world context. Methods: This retrospective, real-world study included patients with advanced or recurrent gynecological tumors with HER2 expression who received RC48 between January 2024 and December 2024.The primary objective is to estimate the objective response rate (ORR) based on the investigator assessment. The study will also assess disease control rate (DCR), progression free survival (PFS) and other outcome measures of RC48 antitumor activity across tumor types. Safety and tolerability will be assessed by the occurrence of AEs and SAEs. Results: From January 2024 to December 2024, a total of 14 eligible patients with HER2-expressing gynecological cancers were enrolled, as a cut-off date(30-Dec-2024), 9 of them completed at least 1 tumor assessment. Of all the patients, 5(35.7%) were HER2(1+) ,6(42.9%) were HER2(2+), and 3(21.4%) were HER2(3+). 8(57.1%)/2(14.3%)/4(28.6%) had 2/3/＞3 prior lines of treatment. 13(92.9%) had FIGO stage III or above disease at diagnosis.13(92.9%) had received taxanes before. 13(92.9%) patients underwent combination therapy(with platinum drugs, PD-1/L1 inhibitors or antiangiogenic drugs). The investigator-assessed (INV) overall ORR was 64.3% (9/14), DCR was 64.3% (9/14). The ORR was 71.4% (5/7) in ovarian cancer, 50.0% (3/6) in cervical cancer, and 100.0% (1/1) in endometrial cancer. Five (35.7%) patients experienced treatment-related adverse events (TRAEs) . The most common TRAEs were fever. Grade≥2 TRAEs occurred in three (21.4%) patients: one patient experienced infusion reaction caused by DV, one patient developed lower limbs motor nerves damage, and the other one patient experienced grade 3 intestinal obstruction. Conclusions: This study provides a novel insight into the clinical outcomes of HER2-expressing advanced or recurrent gynecological tumor patients receiving a RC48 regimen as treatment in a real-world setting. These preliminary results suggest that RC48 has a manageable safety profile and meaningful clinical benefit in pretreated patients with HER2-expressing gynecological cancers.