Prior research on the microbiome has suggested that gut bacteria can influence cancer patients’ response to checkpoint inhibitors (CPIs). Now, Phase I trial data show that use of the live biotherapeutic CBM588 (Clostridium butyricum MIYAIRI 588 strain) plus immunotherapy medicine nivolumab/ipilimumab significantly improved progression-free survival in patients with metastatic kidney cancer when compared to use of nivolumab/ipilimumab alone.

The study was published in Nature Medicine in the paper, “Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase I trial.

“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,” said Sumanta Pal, MD, professor in the department of medical oncology & therapeutics research at City of Hope. “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.”

Sumanta Pal, MD, City of Hope

CBM588 is a bifidogenic live bacterial product that produces short-chain fatty acids (mainly butyric acid), a well-known energy source for the lining of the GI tract and has immunomodulatory properties. The bacterial strain appears to exert additional beneficial effects, including inhibiting pathogenic microorganisms and helping to restore the GI lining and decrease intestinal imbalance.

In the open-label, single-center study (NCT03829111), 30 patients with metastatic kidney cancer (renal cell carcinoma) who had never received treatment before were randomized to receive either CBM588 orally in combination with nivolumab/ipilimumab or nivolumab/ipilimumab alone.

The data show a significant improvement in progression-free survival in patients treated with CBM588 plus nivolumab/ipilimumab (12.7 months) compared to nivolumab/ipilimumab alone (2.5 months). Additionally, use of CBM588 in combination therapy was linked to an increase in response rate when compared to use of nivolumab/ipilimumab therapy alone (58% vs. 20%).

While there was no significant difference between the treatment groups in terms of the amount of the Bifidobacterium genus bacteria, patients who responded to the CBM588 with nivolumab/ipilimumab treatment had significant increases in the Bifidobacterium species. There were no significant differences in treatment-related toxicity reported between the two groups.

“Over the last several years, the immunotherapy field has been closely studying how the GI microbiome can enhance immune checkpoint efficacy for the treatment of cancer,” said Thomas Parks, PhD, director of product development at Osel—the company involved in the study. “Compared to microbiome modulation using fecal transplants, CBM588 given orally is potentially a more effective, reproducible, scalable, and safer method to treat patients. We look forward to supporting the world-class team at City of Hope as they advance CBM588 in additional clinical trials.”

“City of Hope is currently conducting another Phase I clinical trial of CBM588 in combination with nivolumab and tyrosine kinase inhibitor cabozantinib for the treatment of advanced or metastatic kidney cancer,” said Pal. “We are working to open a large, randomized Phase III trial of CBM588 in the future.”

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