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

Antineoplastic Combined Chemotherapy Protocols / adverse effects Carcinoma, Renal Cell / drug therapy Dietary Supplements Female Humans Ipilimumab / therapeutic use Kidney Neoplasms / drug therapy Male Nivolumab / therapeutic use

Journal

Nature medicine

ISSN: 1546-170X

Titre abrégé: Nat Med

Pays: United States

ID NLM: 9502015

Informations de publication

Date de publication:
04 2022

Historique:

received: 26 07 2021

accepted: 13 01 2022

pubmed: 2 3 2022

medline: 22 4 2022

entrez: 1 3 2022

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41591-022-01694-6 PMID: 35228755 PMC: PMC9018425

pubmed: 35228755

doi: 10.1038/s41591-022-01694-6

pii: 10.1038/s41591-022-01694-6

pmc: PMC9018425

doi:

Substances chimiques

Ipilimumab 0

Nivolumab 31YO63LBSN

Banques de données

ClinicalTrials.gov

['NCT03829111']

Types de publication

Clinical Trial, Phase I Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

Pagination

704-712

Subventions

Organisme : NCI NIH HHS

ID : P30 CA033572

Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

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