Treatment-naive RCC patients (n= 29) were randomized 2:1 to receive combination nivolumab plus ipilimumab treatment with or without oral CBM588, a live bifidogenic bacterial product. At data cutoff, the median follow-up time was 12.2 months, 12 patients were still on treatment, and 24 patients were alive. Median PFS was significantly prolonged in the CBM588-treated group (12.7 months versus 2.5 months, hazard ratio 0.15, P<0.001). Disease control was reached in 15 (79%) CBM588-treated patients versus 4 (40%) in the other arm. Exploratory microbiome analyses indicated Bifidobacterium increase in treatment-responsive CMB588-treated patients.
Contributed by Margot O’Toole
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 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.
Author Info: (1) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. Yale University School of Medicine, New Haven, CT, USA. (2) Department of Medical Onc
Author Info: (1) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. Yale University School of Medicine, New Haven, CT, USA. (2) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (3) Cettro Oncologia, Brasilia, Brazil. (4) Department of Immunology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (5) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (6) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (7) Division of Biostatistics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (8) Division of Biostatistics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (9) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (10) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (11) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (12) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (13) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (14) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (15) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (16) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (17) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (18) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (19) The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA. (20) The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA. (21) The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA. (22) Miyarisan Pharmaceuticals, Co., Ltd., Tokyo, Japan. (23) Miyarisan Pharmaceuticals, Co., Ltd., Tokyo, Japan. (24) Miyarisan Pharmaceuticals, Co., Ltd., Tokyo, Japan. (25) Department of Immunology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. (26) The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA. sarah@skhighlander.us. (27) Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. spal@coh.org.
