Open-label, phase 2 study of adebrelimab combined with fuzuloparib in the treatment of patients with HRD-positive, recurrent platinum-resistant ovarian cancer.

Abstract

TPS5634 Background: Adebrelimab, a humanized anti-PD-L1 monoclonal antibody, selectively targets PD-L1 molecules to inhibit the PD-1/PD-L1 pathway, reversing tumor-induced immune tolerance and revitalizing the immune system's capacity to combat tumors. Fuzuloparib, a novel PARP inhibitor, impedes the activity of poly (ADP-ribose) polymerase, halting the DNA repair mechanism for single-stranded breaks, resulting in DNA damage accumulation and consequent cancer cell apoptosis. Emerging evidence strongly supports that PARP inhibitors significantly extend progression-free survival in homologous recombination-deficient (HRD)-positive ovarian cancer. The TOPACIO study demonstrated that the combination of niraparib and pembrolizumab for platinum-resistant ovarian cancer achieved an objective response rate (ORR) of 18%, with durable responses in patients. This underscores the potential of integrating PARP inhibitors with immune checkpoint inhibitors in clinical protocols. For platinum-resistant recurrent ovarian cancer, known for its challenging prognosis, we propose conducting exploratory clinical trials on the combination of adebrelimab and fuzuloparib, aiming to establish robust evidence for future clinical applications. Methods: This open-label, single-arm, Phase 2 study aims to evaluate the anti-tumor activity and safety of adebrelimab in combination with fuzuloparib in approximately 37 patients with HRD-positive, recurrent platinum-resistant epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer (hereinafter referred to as ovarian cancer). The primary endpoint is to determine the objective response rate of the combined treatment regimen, as defined by the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints encompass disease control rate, progression-free survival overall survival, along with the assessment of safety and tolerability. Patients must be aged 18-70 years with an Eastern Cooperative Oncology Group performance status of 0–1 and have recurrent histologically confirmed ovarian cancer with HRD-positive tumor. Patients must have progressed within less than 6 months after the last treatment with platinum-containing chemotherapy. HRD status confirmed by testing BRCA gene, loss of heterozygosity, telomeric allelic imbalance and large-scale transition. Adebrelimab (20 mg/kg) is administered intravenously every 3 weeks and fuzuloparib (100mg) is administered orally twice daily as until the patient experiences disease progression, intolerable toxicity, or other study treatment discontinuation criteria are met. This clinical trial is in progress and 7 patients have been enrolled. Clinical trial information: NCT05753826 .