信迪利单抗联合贝伐珠单抗和卡培他滨/奥沙利铂（BBCAPX）一线治疗 RAS 基因突变、微卫星稳定、转移性结直肠癌患者：一项随机、开放标签、多中心研究的研究方案。
Sintilimab plus bevacizumab and CapeOx (BBCAPX) on first-line treatment in patients with RAS mutant, microsatellite stable, metastatic colorectal cancer: study protocol of a randomized, open-label, multicentric study.
机构信息
Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
出版信息
BMC Cancer. 2023 Jul 18;23(1):676. doi: 10.1186/s12885-023-11139-z.
BACKGROUND
Rat sarcoma viral oncogene homolog (RAS) gene mutation is a common molecular event in colorectal cancer (CRC). The prognosis of mCRC (metastatic colorectal cancer) patients with RAS mutation is poor and capecitabine and oxaliplatin (CapeOx) plus bevacizumab has shown to be one of the standard therapeutic regimens as first line for these patients with objective response rate (ORR) of ~ 50% and median progression-free survival (mPFS) of 8-9 months. Immunotherapy, especially anti-programmed death 1 (PD-1) monoclonal antibody has demonstrated ground-breaking results in deficient mismatch repair (dMMR) / microsatellite instability-high (MSI-H) mCRC patients. However, the response rate of in microsatellite stable (MSS) patients is extremely low. In addition, preclinical studies have demonstrated that anti-Vascular endothelial growth factor (VEGF) agents, such as bevacizumab, can induce tumor vascular normalization and enhance antitumor immunity. Previous study indicated the combination of chemotherapy, anti-VEGF agents (bevacizumab) with immune checkpoint inhibitors may have promising clinical activity in RAS mutant, MSS refractory mCRC patients. Based on these evidences, we will explore the combination of CapeOx with bevacizumab and sintilimab (anti-PD-1 monoclonal antibody) in RAS mutant, MSS mCRC patients as first-line therapy.
METHODS
This is a randomized, open-label, multicentric clinical trial. In the sintilimab arm, patients will receive sintilimab in combination with CapeOx and bevacizumab. In the control arm, patients will receive CapeOx and bevacizumab. This trial will recruit 494 patients from 20 centers and randomly (1:1) disseminated into two groups. The primary endpoint is the PFS. The secondary endpoints include overall survival, safety, ORR, and disease control rate.
DISCUSSION
This study may provide new ideas for optimizing oncology treatment planning for RAS mutant, MSS mCRC patients in the first-line set.
TRIAL REGISTRATION
This study is short for BBCAPX and has been registered at clinicaltrials.gov registry with identifier NCT05171660.
背景
鼠肉瘤病毒癌基因同源物（RAS）基因突变是结直肠癌（CRC）的常见分子事件。RAS 突变的转移性结直肠癌（mCRC）患者的预后较差，卡培他滨和奥沙利铂（CapeOx）联合贝伐珠单抗已被证明是这些患者的标准治疗方案之一，客观缓解率（ORR）约为 50%，中位无进展生存期（mPFS）为 8-9 个月。免疫疗法，特别是抗程序性死亡 1（PD-1）单克隆抗体，在错配修复缺陷（dMMR）/微卫星高度不稳定（MSI-H）mCRC 患者中显示出突破性的结果。然而，在微卫星稳定（MSS）患者中的反应率极低。此外，临床前研究表明，抗血管内皮生长因子（VEGF）药物，如贝伐珠单抗，可诱导肿瘤血管正常化并增强抗肿瘤免疫。先前的研究表明，化疗、抗 VEGF 药物（贝伐珠单抗）与免疫检查点抑制剂联合可能在 RAS 突变、MSS 难治性 mCRC 患者中具有有前景的临床活性。基于这些证据，我们将探索 CapeOx 联合贝伐珠单抗和信迪利单抗（抗 PD-1 单克隆抗体）在 RAS 突变、MSS mCRC 患者中的一线治疗。
方法
这是一项随机、开放标签、多中心临床试验。在信迪利单抗组中，患者将接受信迪利单抗联合 CapeOx 和贝伐珠单抗治疗。在对照组中，患者将接受 CapeOx 和贝伐珠单抗治疗。该试验将从 20 个中心招募 494 名患者，并随机（1:1）分为两组。主要终点是无进展生存期（PFS）。次要终点包括总生存期、安全性、ORR 和疾病控制率。
讨论
这项研究可能为 RAS 突变、MSS mCRC 患者一线治疗方案的肿瘤治疗计划优化提供新的思路。
试验注册
本研究简称 BBCAPX，已在 clinicaltrials.gov 注册，登记号为 NCT05171660。
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