创作:aluba 审核:aluba 2022年04月01日
  • 29名未经治疗的转移性肾细胞癌患者随机分组,在接受纳武单抗+伊匹单抗治疗的同时,其中19名患者每日口服CBM588;
  • 干预12周后,相比于对照组,CBM588组患者的肠道菌群中的双歧杆菌属丰度未显著增加,但CBM588组应答患者的双歧杆菌属丰度显著增加;
  • 相比于对照组,CBM588组患者的无进展生存期显著延长(12.7个月 vs. 2.5个月),客观应答率非显著地升高(58% vs. 20%);
  • 两组之间的3级及4级不良事件发生率无显著差异(50% vs. 52%)。
CBM588是一种含有丁酸梭菌的活菌产品。Nature Medicine上发表的一项临床1期研究结果,在29名转移性肾细胞癌患者中发现,补充CBM588可增强纳武单抗+伊匹单抗的疗效,显著延长患者的无进展生存期。
Nature Medicine [IF:87.241]

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



2022-02-28, Article

Abstract & Authors:展开

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 12 weeks 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 2.5 months, 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.

First Authors:
Nazli Dizman,Luis Meza,Paulo Bergerot

Correspondence Authors:
Sarah K Highlander,Sumanta K Pal

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