Efficacy and safety of distamab vedotin combined with carboplatin and bevacizumab for HER2-expressing platinum-sensitive ovarian cancer with prior PARPi treatment.

Abstract

e17580 Background: Disitamab Vedotin (DV) is a newly developed antibody-drug conjugate targeting human epidermal growth factor 2 (HER2) that is comprised of hertuzumab coupling monomethyl auristatin E(MMAE) via a cleavable linker. It has been approved in HER2-expressing urothelial and gastric cancers. The increasing use of PolyADP-ribose polymerase inhibitors (PARPis) in clinical practice for ovarian cancer raised the issue of PARPis resistance, disease relapse and dismal prognosis for patients. New treatments are needed for platinum-sensitive ovarian cancer (PSOC) patients who have received PARPi maintenance therapy after front lines of chemotherapy. The aim of this study (ChiCTR2400084761) was to assess efficacy and safety of MMAE-ADC RC48 combined with platinum in patients with HER2-expressing PSOC. Methods: Participants with confirmed HER2-expressing (IHC3+, 2+or 1+) ovarian cancer that had experienced platinum-sensitive recurrence were enrolled. After RC48 combined with carboplatin for at least 4~6 cycles (with or without bevacizumab), then maintenance with RC48(with or without bevacizumab) was administered until disease progression or unacceptable toxicity. Primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety. Results: At the time of data cutoff (January 14, 2025), 10 eligible patients were enrolled and 7 of them completed at least 1 tumor assessment. Of all the patients, 7 were HER2 (1+) and 3 were HER2 (2+). Most patients (90%) had FIGO stage III OC at diagnosis. 60% of the patients relapsed from first-line PARPi maintenance treatment and 40% of patients relapsed from ≥2 systematic treatment. All had received taxanes and platinum before. The median duration of PARPi in the entire cohort was 11.5 (4.9-30.7) months. Patients had a median Platinum Free Interval (PFI) after last platinum therapy of 9.2 (6.3-35.3) months. Of all the patients who completed at least 1 tumor assessment ,5 received PR, 1 received SD, and 1 received PD. The overall ORR was 71.4% (5/7) and DCR was 85.7% (6/7). Most common treatment-related AEs were leukopenia, neutropenia and AST/ALT increase. The most common grade 3 or higher drug related AEs were neutropenia (71.4%) . No new safety signals were identified, and there were no deaths related to RC48. Conclusions: The preliminary data demonstrated notable efficacy in this pretreated PSOC population, including among those who may have PARPi resistance. DV combined with carboplatin and bevacizumab demonstrated manageable safety consistent with the known profile. The clinical trial is on-going. Clinical trial information: ChiCTR2400084761 .