Biomarker-driven targeted therapy in patients with recurrent platinum-resistant epithelial ovarian cancer (BRIGHT): protocol for an open-label, multicenter, umbrella study

Abstract

BackgroundPlatinum-resistant, recurrent ovarian cancer has an abysmal prognosis with limited treatment options. Poly-(ADP-ribose)-polymerase (PARP), angiogenesis, and immune checkpoint inhibitors might improve the outcomes of platinum-resistant, recurrent ovarian cancer, but accurate patient selections for those therapies remain a significant clinical challenge.Primary ObjectiveTo evaluate the efficacy and safety of biomarker-driven combinatorial therapies of pamiparib, tislelizumab, bevacizumab, and nab-paclitaxel in platinum-resistant, recurrent ovarian cancer.Study HypothesisA precision medicine combination of PARP inhibitors, anti-angiogenic therapy, immunotherapy, and chemotherapy will improve disease outcomes of platinum-resistant, recurrent ovarian cancer by accounting for genomic and immunologic features.Trial DesignThe BRIGHT Trial is a prospective, open-label, multicenter, phase II, umbrella study planning to enroll 160 patients with serous, endometrioid, or clear cell platinum-resistant, recurrent ovarian cancer from 11 clinical centers in China. Patients are assigned to one of three experimental arms based on biomarkers. Patients withBRCA1/2mutations will receive pamiparib plus bevacizumab (arm 1, n=40) regardless of CD8+tumor-infiltrating lymphocytes count. Patients with wild-typeBRCA1/2(BRCAwt) and ≥3 CD8+tumor-infiltrating lymphocytes count will receive the combination of tislelizumab, bevacizumab, and nab-paclitaxel (arm 2, n=50), whileBRCAwtpatients with <3 CD8+tumor-infiltrating lymphocytes count will receive bevacizumab plus dose-dense nab-paclitaxel (arm 3, n=50). After completing patient enrollment in arm 2, another 20BRCAwtpatients with ≥3 CD8+tumor-infiltrating lymphocytes count will be included as an arm 2 expansion. Treatment will continue until disease progression or intolerable toxicity, and all adverse events will be recorded.Major Inclusion/Exclusion CriteriaEligible patients include those aged ≥18 with serous, endometrioid, or clear cell ovarian cancer, platinum-resistant recurrence, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.Primary EndpointObjective response rate (ORR) assessed by the investigators by the RECIST 1.1 criteria.Sample Size160 patients.Estimated Dates for Completing Accrual and Presenting ResultsRecruitment is estimated to be completed by 2024 and results may be published by 2027.Trial RegistrationClinicalTrials.gov:NCT05044871.