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Biomarker-driven targeted therapy in patients with recurrent platinum-resistant epithelial ovarian cancer (BRIGHT): protocol for an open-label, multicenter, umbrella study
  1. Yu Xu1,2,
  2. Fan Xiong1,2,
  3. Huayi Li1,2,
  4. Hong Zheng3,
  5. Jie Jiang4,
  6. Qingshui Li5,
  7. Guiling Li6,
  8. Weidong Zhao7,
  9. Rong Li8,
  10. Jundong Li9,
  11. Rong Xie10,
  12. Ruifang An11,
  13. Huifeng Zhang12 and
  14. Qinglei Gao1,2
    1. 1National Clinical Research Center for Obstetrics and Gynecology, Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    2. 2Cancer Biology Research Center (Key Laboratory of the Ministry of Education, Hubei Provincial Key Laboratory of Tumor Invasion and Metastasis), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    3. 3Department of Gynecology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital, Beijing, China
    4. 4Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, China
    5. 5Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Jinan, China
    6. 6Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    7. 7Department of Gynecological Oncology, Anhui Provincial Cancer Hospital, Hefei, China
    8. 8Gynecological Oncology Center, Chongqing University Cancer Hospital, Chongqing, China
    9. 9Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
    10. 10Department of Gynecology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China
    11. 11Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
    12. 12Department of Gynecologic Oncology, Hubei Cancer Hospital, Wuhan, China
    1. Correspondence to Dr Qinglei Gao, National Clinical Research Center for Obstetrics and Gynecology, Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; qingleigao{at}hotmail.com; Dr Huifeng Zhang, Department of Gynecologic Oncology, Hubei Cancer Hospital, Wuhan, China; zhanghuifen29{at}163.com; Dr Ruifang An, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; anruifang{at}163.com

    Abstract

    Background 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.

    Primary Objective To evaluate the efficacy and safety of biomarker-driven combinatorial therapies of pamiparib, tislelizumab, bevacizumab, and nab-paclitaxel in platinum-resistant, recurrent ovarian cancer.

    Study Hypothesis 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.

    Trial Design 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.

    Major Inclusion/Exclusion Criteria 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.

    Primary Endpoint Objective response rate (ORR) assessed by the investigators by the RECIST 1.1 criteria.

    Sample Size 160 patients.

    Estimated Dates for Completing Accrual and Presenting Results Recruitment is estimated to be completed by 2024 and results may be published by 2027.

    Trial Registration ClinicalTrials.gov: NCT05044871.

    • Ovarian Cancer
    • Homologous recombination

    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • YX, FX, HL, HZhe and JJ contributed equally.

    • Contributors QG, YX, FX, and HL developed the study concept and protocol. HZhe and JJ assisted in further development of the protocol. QL, GL, WZ, RL, JL, RX, RA, HZha, and QG are responsible for the supervision of the clinical trial. QG has access to the final trial dataset. QG acts as a guarantor. All authors contributed to the article and approved the submitted version.

    • Funding This work was supported by the National Key Technology Research and Development Programme of China (2022YFC2704200 and 2022YFC2704205), Beijing Xisike Clinical Oncology Research Foundation (Y-2019AZZD-0359), and National Natural Science Foundation of China (82072889 and 82372928).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; internally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.