CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Biomarker-driven targeted therapy in patients with recurrent platinum-resistant epithelial ovarian cancer (BRIGHT): protocol for an open-label, multicenter, umbrella study.
Biomarker-driven targeted therapy in patients with recurrent platinum-resistant epithelial ovarian cancer (BRIGHT): protocol for an open-label, multicenter, umbrella study.
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铂耐药复发性卵巢癌预后极差，治疗选择有限。聚（ADP-核糖）聚合酶（PARP）抑制剂、抗血管生成药物和免疫检查点抑制剂可能改善铂耐药复发性卵巢癌的结局，但为这些疗法准确筛选患者仍是一项重大的临床挑战。主要目的：评估基于生物标志物驱动的帕米帕利、替雷利珠单抗、贝伐珠单抗和白蛋白结合型紫杉醇联合疗法在铂耐药复发性卵巢癌中的疗效和安全性。研究假设：PARP抑制剂、抗血管生成治疗、免疫治疗和化疗的精准医学联合方案将通过考虑基因组和免疫学特征来改善铂耐药复发性卵巢癌的疾病结局。试验设计：BRIGHT试验是一项前瞻性、开放标签、多中心、II期伞式研究，计划从中国11个临床中心入组160例浆液性、子宫内膜样或透明细胞铂耐药复发性卵巢癌患者。患者根据生物标志物被分配至三个实验组之一。携带BRCA1/2突变的患者将接受帕米帕利联合贝伐珠单抗治疗（第1组，n=40），无论CD8+TIL（肿瘤浸润淋巴细胞）计数如何。BRCA1/2野生型（BRCAwt）且CD8+TIL（肿瘤浸润淋巴细胞）计数≥3的患者将接受替雷利珠单抗、贝伐珠单抗和白蛋白结合型紫杉醇联合治疗（第2组，n=50），而CD8+TIL（肿瘤浸润淋巴细胞）计数<3的BRCAwt患者将接受贝伐珠单抗联合剂量密集白蛋白结合型紫杉醇治疗（第3组，n=50）。第2组患者入组完成后，将再纳入20例CD8+TIL（肿瘤浸润淋巴细胞）计数≥3的BRCAwt患者作为第2组扩展队列。治疗将持续至疾病进展或出现不可耐受的毒性，所有不良事件都将被记录。主要入组/排除标准：符合条件的患者包括年龄≥18岁、患有浆液性、子宫内膜样或透明细胞卵巢癌、铂耐药复发、东部肿瘤协作组（ECOG）体能状态评分为0或1的患者。主要终点：由研究者根据RECIST 1.1标准评估的客观缓解率（ORR）。样本量：160例患者。预计完成入组和展示结果的日期：预计入组将于2024年完成，结果可能于2027年发表。
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.
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