CBM588 improves the efficacy of first-line treatment with nivolumab and ipilimumab in patients with metastatic renal cell carcinoma (mRCC), according to research presented at IKCS North America 2022.¹

CBM588, a live bacterial product that contains the butyrate-producing bacterium Clostridium butyricum, improved the disease control rate (DCR) and prolonged progression-free survival (PFS) when added to nivolumab and ipilimumab, researchers found.

The researchers conducted this phase 1b trial (ClinicalTrials.gov Identifier: NCT03829111) in treatment-naive mRCC patients with clear cell and/or sarcomatoid histology and intermediate- or poor-risk disease. Patients were randomly assigned (2:1) to receive nivolumab-ipilimumab with daily oral CBM588 or without it.

A prior analysis from this study showed that CBM588 modulated the gut microbiome and improved clinical outcomes.² At that time, the median PFS was 12.7 months with CBM588 and 2.5 months without it (hazard ratio [HR], 0.15, 95% CI, 0.05-0.47; P =.001).

At IKCS North America 2022, Nazli Dizman, MD, of Yale School of Medicine in New Haven, Connecticut, reported long-term follow-up data from the trial.¹ Of the initial 30 patients, 29 were included in the final analysis.

There were 19 patients in the CBM588 arm and 10 in the control arm. The median age at baseline was 66 years in the CBM588 arm and 64 years in the control arm. Most patients were men (68% and 80%, respectively), had intermediate-risk disease (89% and 70%, respectively), and had clear cell histology (63% and 70%, respectively).

The overall response rate (ORR) was numerically higher and the DCR was significantly higher in the CBM588 arm than in the control arm. The ORR was 58% and 20%, respectively (P =.06). The DCR was 79% and 20%, respectively (P =.004). All responses were partial responses.

The median PFS was significantly longer in the CBM588 arm than in the control arm — 36.4 months and 2.5 months, respectively (HR, 0.10; 95% CI, 0.03-0.33; P <.001).

The median overall survival was not reached in either arm. At the data cutoff, 82.8% of the cohort was alive.

Adverse events (AEs) occurred in 100% of patients in the CBM588 arm and 90% of those in the control arm. The rate of grade 2 or higher AEs was 63% and 50%, respectively. There were no new safety signals with long-term use of nivolumab-ipilimumab plus CBM588.

“[A]lthough limited by the sample size, combination of nivolumab, ipilimumab, and CBM588 demonstrated superior clinical outcomes over nivolumab and ipilimumab,” Dr Dizman said. “Progression-free survival and objective response rate with nivolumab, ipilimumab, and CBM588 also exceeded those observed with nivolumab and ipilimumab in historical datasets.”

Disclosures: Osel Inc. provided the CBM588 for this study. Dr Dizman did not provide any disclosures.

References

1. Dizman N. Clinical outcomes with nivolumab/ipilimumab with or without CBM588 in metastatic renal cell carcinoma: Long-term follow-up of a randomized phase Ib clinical trial. Presented at IKCS North America 2022. November 4-5, 2022. Abstract 6.

2. 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 Cancer Therapy Advisor