Neoadjuvant disitamab vedotin plus carboplatin in HER2-expressing advanced ovarian cancer: A prospective, single-arm, phase II trial.

Abstract

5556 Background: Standard neoadjuvant paclitaxel-carboplatin for advanced ovarian cancer causes significant neurotoxicity impacting quality of life. Disitamab vedotin (RC48), an anti-HER2 antibody-drug conjugate, demonstrated efficacy and favorable tolerability in HER2-expressing solid tumors. We evaluated RC48 plus carboplatin as neoadjuvant therapy in HER2-expressing advanced ovarian cancer. Methods: This single-arm phase II trial (NCT06574763) enrolled patients with newly diagnosed FIGO stage III-IV high-grade serous ovarian, fallopian tube, or primary peritoneal cancer expressing HER2 (IHC 1+ or ERBB2 amplification) who were ineligible for primary cytoreductive surgery. Treatment comprised carboplatin (AUC 5, day 1, Q3W) alone in cycle 1, then RC48 (2.5 mg/kg, day 1, Q3W) plus carboplatin for cycles 2-4. A 6-patient safety run-in determined optimal RC48 dosing. Interval debulking surgery (IDS) was performed 14-28 days after cycle 4. Primary endpoint: complete resection rate (CRR, defined as no macroscopic residual disease at IDS). Secondary endpoints: pathological complete response (pCR), objective response rate (ORR per RECIST v1.1), progression-free survival, overall survival, and safety (CTCAE v5.0). Results: From October1st, 2024 to December 31st, 2025, 33 patients were enrolled.; 25 completed neoadjuvant therapy and underwent IDS. Among 24 evaluable patients (1 excluded for mixed histology meeting exclusion criteria), median age was 57 years (range 42-71); all had stage IIIC (n=18, 75%) or IVB (n=6, 25%) disease. The regimen achieved exceptional surgical outcomes: CRR 91.6% (22/24), with 2 patients having minimal residual disease <1 cm. ORR was 87.5% (21/24). pCR rate was 4.2% (1/24). Robust tumor regression was observed: median residual viable tumor in primary lesions 22% (range 0-80%), in omental implants 44% (range 0-80%). With median follow-up of 5.0 months (range 2.3-10.6), no disease recurrence occurred. Grade ≥3 treatment-related adverse events occurred in 29.2% of patients, primarily hematological toxicities (neutropenia, thrombocytopenia) that resolved to ≤grade 2 within one week with supportive care. Critically, no patient (0/27, 0%) experienced peripheral neuropathy of any grade. Conclusions: Neoadjuvant disitamab vedotin plus carboplatin demonstrated exceptional surgical outcomes with 91.6% complete resection rate and complete elimination of neurotoxicity in HER2-expressing advanced ovarian cancer. The regimen induced substantial pathological regression with a favorable safety profile. These results support RC48-carboplatin as a promising neurotoxicity-sparing alternative to standard paclitaxel-based therapy. Updated survival data will be presented. Clinical trial information: NCT06574763 .