%0 Clinical Trial Protocol
%T Biomarker-driven targeted therapy in patients with recurrent platinum-resistant epithelial ovarian cancer (BRIGHT): protocol for an open-label, multicenter, umbrella study.
%A Xu Y
%A Xiong F
%A Li H
%A Zheng H
%A Jiang J
%A Li Q
%A Li G
%A Zhao W
%A Li R
%A Li J
%A Xie R
%A An R
%A Zhang H
%A Gao Q
%J Int J Gynecol Cancer
%V 34
%N 9
%D 2024 Sep 2
%M 38658024
%F 4.661
%R 10.1136/ijgc-2024-005351
%X <B>BACKGROUND: </B>Platinum-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.<BR><B>OBJECTIVE: </B>To evaluate the efficacy and safety of biomarker-driven combinatorial therapies of pamiparib, tislelizumab, bevacizumab, and nab-paclitaxel in platinum-resistant, recurrent ovarian cancer.<BR><B>OBJECTIVE: </B>A 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.<BR><B>METHODS: </B>The 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 with BRCA1/2 mutations will receive pamiparib plus bevacizumab (arm 1, n=40) regardless of CD8+ tumor-infiltrating lymphocytes count. Patients with wild-type BRCA1/2 (BRCAwt) and ≥3 CD8+ tumor-infiltrating lymphocytes count will receive the combination of tislelizumab, bevacizumab, and nab-paclitaxel (arm 2, n=50), while BRCAwt patients 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 20 BRCAwt patients 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.<BR><B>UNASSIGNED: </B>Eligible 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.<BR><B>METHODS: </B>Objective response rate (ORR) assessed by the investigators by the RECIST 1.1 criteria.<BR><B>METHODS: </B>160 patients.<BR><B>UNASSIGNED: </B>Recruitment is estimated to be completed by 2024 and results may be published by 2027.<BR><B>BACKGROUND: </B>ClinicalTrials.gov: NCT05044871.