Preliminary analysis of disitamab vedotin combined therapy for HER2-expressing platinum-sensitive recurrent ovarian/peritoneal/fallopian tube cancer (Diversity study): A single-arm, multicenter phase II trial.

5564 Background: Platinum-sensitive recurrent epithelial ovarian/peritoneal/fallopian tube cancer (PSROC) patients often exhibit reduced responsiveness to chemotherapy following initial platinum-based regimens, necessitating the development of more effective treatment strategies. Disitamab vedotin (DV; RC48) is a novel humanized anti-HER2 antibody-drug conjugate (ADC) with greater specificity than conventional agents like paclitaxel. This study (NCT06420973) evaluates the efficacy and safety of DV-based combination therapy in patients with HER2-expressing PSROC. Methods: This single-arm, open-label, multicenter phase II study examines DV combination therapy in patients with HER2-expressing (IHC 1 to 3+) PSROC. Patients received DV (2.5 mg/kg) plus carboplatin (AUC 5), with or without bevacizumab (7.5–15 mg/kg), every 21 days for six cycles. Maintenance therapy included DV (up to eight cycles) with or without bevacizumab until disease progression. The primary endpoint is PFS. Secondary endpoints include ORR, DCR, OS and safety. An exploratory endpoint assesses quality of life using the EORTC QLQ-CIPN20 (excluding Item 20). Results: As of January 2025, 15 patients (median age 58 years, range 47-73) were enrolled, with 86.7% diagnosed with ovarian cancer and 93.3% having high-grade serous carcinoma. Genetic analysis identified 4 gBRCA1 mutations, 1 sBRCA2 mutation, 5 wild-type cases, and 5 with unknown status. HER2 expression was 73% for IHC 1+ and 27% for 2+. The median number of prior treatment lines was one, with a median follow-up of 3.2 months (range 1-6.8m). Efficacy was evaluated in 10 patients, while safety was assessed in all 15. The ORR was 70% (1 CR, 6 PR), with a DCR of 100%. The ORR for both BRCA mutations and wild-type was 66.7%. Among patients with HER2 IHC 1+, the ORR was 71.4%, while for 2+, it was 66.6%. Patients with PFI >12 months had a 75% ORR, compared to 50% for those PFI <12 months. Treatment-related adverse events (TRAEs) were reported in 80% of patients, with ≥ Grade 3 TRAEs at 26.7%, including neutropenia (n=1), thrombocytopenia (n=2), and diarrhea (n=1). No Grade 4 or 5 TRAEs were observed. The EORTC QLQ-CIPN20 score showed no significant impact on quality of life compared to baseline. As of January 23, 2024, one patient had disease progression. Conclusions: The preliminary findings indicate that DV combined therapy is effective and safe for the treatment of HER2-expressing PSROC, highlighting its potential as a valuable therapeutic option. Further research in this area is essential to validate these results. Clinical trial information: NCT06420973 .