抗程序性细胞死亡蛋白1抗体加多激酶抑制剂在多种肿瘤类型中显示出令人鼓舞的活性，包括结直肠癌。本研究评估了雷可莫芬和尼伐替尤在微卫星稳定/错配修复高水平的转移性结直肠癌患者中的应用。这项单臂、开放标签、多中心2期研究在美国的13个BYS参与站招募了已接受过治疗的微卫星稳定/错配修复高水平的晚期结直肠癌成年人体。符合条件的患者已知具有扩展的RAS/ BRAF状态、对不超过2条（对于扩展的RAS突变）或3条（对于扩展的RAS野生型）系统化疗耐药性或不耐受性和东方合作组织肿瘤诊疗小组的治疗效果分级为零或一。雷可莫芬口服每天80毫克，停药1周，连续3周（如果耐受良好，则增加至每天120毫克），同时给予每4周一次的静脉注射尼伐替尤480毫克。主要终点为客观缓解率。次要终点包括安全性、总生存期和无进展生存期。探索性终点包括与抗肿瘤活性相关的生物标志物。接受至少一剂研究干预的患者包括在疗效和安全性分析中。在第一年的每8周进行一次肿瘤评估，在此之后每12周进行一次肿瘤评估，直至疾病进展/研究结束，并在所有患者达到基线后五次扫描标准和十个月的随访或退出后分析客观缓解率。该试验已在ClinicalTrials.gov登记，编号为NCT04126733.从2019年10月14日至2020年1月14日，共有94名患者入选，70名患者接受了治疗。五名患者出现部分缓解，客观缓解率为7％（95％ CI为2.4-15.9; p = 0.27）。所有缓解患者在基线时没有肝转移。中位总生存期（数据不足）和无进展生存期分别为11.9个月（95％ CI 7.0-不可评估）和1.8个月（95％ CI 1.8-2.4）。大多数患者（97％，68/70）经历了与治疗相关的不良事件；51％为1级或2级，40％为3级，3％为4级，3％为5级。最常见的（≥20％）事件是疲劳（26/70）、手掌-足底红皮病综合征（19/70）、斑疹样皮疹（17/70）、增加的血胆红素（14/70）和食欲减退（14/70）。肿瘤免疫敏感性的生物标志物的基线表达较高与抗肿瘤活性相关联。需要进一步的研究以确定临床特征或生物标志物的亚组，这些患者最能从雷可莫芬加尼伐替尤治疗中获益。Bayer/Bristol Myers Squibb。©2023年作者。

Anti-programmed cell death protein 1 antibodies plus multikinase inhibitors have shown encouraging activity in several tumour types, including colorectal cancer. This study assessed regorafenib plus nivolumab in patients with microsatellite stable/mismatch repair-proficient metastatic colorectal cancer.This single-arm, open-label, multicentre phase 2 study enrolled adults from 13 sites in the USA with previously treated advanced microsatellite stable/mismatch repair-proficient metastatic colorectal cancer. Eligible patients had known extended RAS and BRAF status, progression or intolerance to no more than two (for extended RAS mutant) or three (for extended RAS wild type) lines of systemic chemotherapy and an Eastern Cooperative Oncology Group performance status of 0 or 1. Regorafenib 80 mg/day was administered orally for 3 weeks on/1 week off (increased to 120 mg/day if 80 mg/day was well tolerated) with intravenous nivolumab 480 mg every 4 weeks. Primary endpoint was objective response rate. Secondary endpoints included safety, overall survival, and progression-free survival. Exploratory endpoints included biomarkers associated with antitumour activity. Patients who received at least one dose of study intervention were included in the efficacy and safety analyses. Tumour assessments were carried out every 8 weeks for the first year, and every 12 weeks thereafter until progressive disease/end of the study, and objective response rate was analysed after all patients had met the criteria for primary completion of five post-baseline scans and either 10-months' follow-up or drop out. This trial is registered with ClinicalTrials.gov, number NCT04126733.Between 14 October 2019 and 14 January 2020, 94 patients were enrolled, 70 received treatment. Five patients had a partial response, yielding an objective response rate of 7% (95% CI 2.4-15.9; p = 0.27). All responders had no liver metastases at baseline. Median overall survival (data immature) and progression-free survival were 11.9 months (95% CI 7.0-not evaluable) and 1.8 months (95% CI 1.8-2.4), respectively. Most patients (97%, 68/70) experienced a treatment-related adverse event; 51% were grade 1 or 2, 40% were grade 3, 3% were grade 4, and 3% were grade 5. The most common (≥20%) events were fatigue (26/70), palmar-plantar erythrodysesthesia syndrome (19/70), maculopapular rash (17/70), increased blood bilirubin (14/70), and decreased appetite (14/70). Higher baseline expression of tumour biomarkers of immune sensitivity correlated with antitumour activity.Further studies are warranted to identify subgroups of patients with clinical characteristics or biomarkers that would benefit most from treatment with regorafenib plus nivolumab.Bayer/Bristol Myers Squibb.© 2023 The Authors.