Bacterial Supplement May Improve CPI Outcomes in Metastatic Kidney Cancer

3D rendering of human intestine villi and microbiome
In a phase 1 trial, investigators tested whether an oral supplement containing a strain of Clostridium butyricum increases the abundance of certain gut bacteria known to be associated with a better response to immune checkpoint inhibitors.

Results from a small study suggest that a live bacterial supplement might improve outcomes in patients receiving checkpoint inhibitor (CPI) immunotherapy for advanced kidney cancer, possibly by increasing the abundance of certain beneficial bacteria.

Data from an open-label phase 1 trial demonstrate that use of a live strain of Clostridium butyricum (CBM588) orally in combination with the CPIs nivolumab/ipilimumab significantly improved progression-free survival (PFS) in patients with metastatic renal cell carcinoma (mRCC) compared with nivolumab/ipilimumab alone, investigators reported in Nature Medicine.

“To our knowledge, this is the first randomized clinical trial to demonstrate that a live bacterial product can modulate the gastrointestinal microbiome and enhance immunotherapy response in cancer patients,” the study’s senior author Sumanta K. Pal, MD, a professor in the Department of Medical Oncology & Therapeutics Research at City of Hope in Duarte, California, said in a press release. “These results can help improve treatment options for patients with kidney cancer and is an important foundational step to bring about more effective targeted therapies for cancer treatment.”

The study included 30 treatment-naive patients with mRCC who had clear cell and/or sarcomatoid histology and intermediate- or poor-risk disease. Investigators randomly assigned patients 2:1 to receive nivolumab/ipilimumab with or without daily oral CBM588, respectively. PFS was significantly longer in patients among the CBM588 recipients compared with those not receiving the bacterial supplement (12.7 vs 2.5 months). CBM588 was significantly associated with an 85% decreased risk for progression.

Dr Pal’s team tested whether use of CBM588 could improve CPI response by increasing the relative abundance of Bifidobacterium species in the gut. Previous studies have shown that Bifidobacterium species are associated with enhanced clinical benefit from CPIs. The investigators found no significant difference in the abundance of Bifidobacterium species between treatment arms overall, but did note significant increases in patients who responded to CBM588 plus nivolumab/ipilimumab. The groups did not differ significantly with respect to treatment-related toxicity.

The bacterial supplement is being developed by Osel, Inc.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Dizman N, Meza L, Bergerot P, et al. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nat Med. Published online February 28, 2022. doi:10.1038/s41591-022-01694-6

This article originally appeared on Renal and Urology News