小柯机器人

美国希望之城综合癌症中心Sumanta K. Pal、转化基因组学研究院Sarah K. Highlander等研究人员合作完成nivolumab加Ipilimumab联合补充活细菌补充治疗转移性肾细胞癌的临床试验。2022年2月28日，《自然—医学》杂志在线发表了这项成果。

据研究人员介绍。以前的研究表明，肠道微生物组影响着癌症患者对检查点抑制剂（CPI）的反应。CBM588是一种双歧因子活菌产品，研究人员推测它可以通过调节肠道微生物组来增强CPI反应。

在一项开放标签的单中心研究（NCT03829111）中，30名治疗无效的透明细胞和/或肉瘤组织学的转移性肾细胞癌患者，以2:1的比例随机接受nivolumab和ipilimumab，分别每日口服CBM588或不接受。在多个时间点进行了粪便元基因组测序。比较基线和12周时双歧杆菌的相对丰度的主要终点没有达到，也没有检测到双歧杆菌或与nivolumab-ipilimumab联用CBM588相关的Shannon指数差异。次要终点包括反应率、无进展生存期（PFS）和毒性。接受nivolumab-ipilimumab和CBM588病人的PFS明显长于不接受的病人（12.7个月 vs 2.5个月，风险比0.15，95%置信区间0.05-0.47，P=0.001）。虽然没有统计学意义，但接受CBM588的患者反应率也更高（58% vs 20%，P=0.06）。在研究组之间没有观察到毒性的明显差异。

这些数据表明，CBM588似乎能提高接受nivolumab-ipilimumab治疗的转移性肾细胞癌患者临床结果。有必要进行更大规模的研究，以证实这一临床观察，并阐明其作用机制和对微生物组和免疫区的影响。

附：英文原文

Title: Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial

Author: Dizman, Nazli, Meza, Luis, Bergerot, Paulo, Alcantara, Marice, Dorff, Tanya, Lyou, Yung, Frankel, Paul, Cui, Yujie, Mira, Valerie, Llamas, Marian, Hsu, Joann, Zengin, Zeynep, Salgia, Nicholas, Salgia, Sabrina, Malhotra, Jasnoor, Chawla, Neal, Chehrazi-Raffle, Alex, Muddasani, Ramya, Gillece, John, Reining, Lauren, Trent, Jeff, Takahashi, Motomichi, Oka, Kentaro, Higashi, Seiya, Kortylewski, Marcin, Highlander, Sarah K., Pal, Sumanta K.

Issue&Volume: 2022-02-28

Abstract: Previous studies have suggested that the gut microbiome influences the response to checkpoint inhibitors (CPIs) in patients with cancer. CBM588 is a bifidogenic live bacterial product that we postulated could augment CPI response through modulation of the gut microbiome. In this open-label, single-center study (NCT03829111), 30 treatment-naive patients with metastatic renal cell carcinoma with clear cell and/or sarcomatoid histology and intermediate- or poor-risk disease were randomized 2:1 to receive nivolumab and ipilimumab with or without daily oral CBM588, respectively. Stool metagenomic sequencing was performed at multiple timepoints. The primary endpoint to compare the relative abundance of Bifidobacterium spp. at baseline and at 12weeks was not met, and no significant differences in Bifidobacterium spp. or Shannon index associated with the addition of CBM588 to nivolumab–ipilimumab were detected. Secondary endpoints included response rate, progression-free survival (PFS) and toxicity. PFS was significantly longer in patients receiving nivolumab–ipilimumab with CBM588 than without (12.7 months versus 2.5months, hazard ratio 0.15, 95% confidence interval 0.05–0.47, P=0.001). Although not statistically significant, the response rate was also higher in patients receiving CBM588 (58% versus 20%, P=0.06). No significant difference in toxicity was observed between the study arms. The data suggest that CBM588 appears to enhance the clinical outcome in patients with metastatic renal cell carcinoma treated with nivolumab–ipilimumab. Larger studies are warranted to confirm this clinical observation and elucidate the mechanism of action and the effects on microbiome and immune compartments.

DOI: 10.1038/s41591-022-01694-6

Source: https://www.nature.com/articles/s41591-022-01694-6

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
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