Dr Ebrahimi on Clinical Outcomes With the Addition of CBM588 to Cabozantinib and Nivolumab in RCC

“We hypothesized that the addition of CBM588 [to cabozantinib and nivolumab] would result in an increase in Bifidobacterium species in experimental arm. What we saw was that neither the experimental nor control arm had any significant difference in the abundance of Bifidobacterium species at week 13 compared with baseline. However, we saw that the median PFS…and the overall response rate were higher in experimental arm.”

Hedyeh Ebrahimi, MD, MPH, postdoctoral fellow, City of Hope Comprehensive Cancer Center, discusses clinical- and microbiome-related outcomes observed with the addition of CBM588 to cabozantinib (Cabometyx) and nivolumab (Opdivo) in patients with metastatic renal cell carcinoma, according to updated data from a phase 1 study (NCT05122546).

Previous data published from the study in Nature indicated that the addition of CBM588 to cabozantinib plus nivolumab did not lead to a difference in the relative abundance of Bifidobacterium spp. or alpha diversity, failing to meet the study’sprimary microbiome-related end point. However, results from an updated analysis shared during the 2025 Genitourinary Cancers Symposium showed that the addition of CBM588 demonstrated clinical benefits in progression-free survival (PFS) and objective response rate, she reports.

As observed in the prior analysis, there was no statistically significant difference in Bifidobacterium spp. abundance between baseline and week 13 in either the experimental arm (n = 20; P = .3894) or the control arm (n = 10; P = .9453) per Wilcoxon matched-pairs test, Ebrahimi says. Similarly, no significant difference in alpha diversity was observed between baseline and week 13 in the experimental (P = .65) or control (P = .17) arms using the Kruskal-Wallis test.

Despite the lack of observed microbiome alterations, CBM588 plus cabozantinib and nivolumab was associated with improved clinical outcomes, Ebrahimi details. In the CBM588/cabozantinib/nivolumab cohort, the median PFS was 19.7 months vs 13.4 months in the cabozantinib/nivolumab-only cohort (HR, 0.74; 95% CI, 0.25-2.23; P = .59). The partial response rate in the CBM588 group was 84% compared with 20% in the control group. The stable disease and progressive disease rates were 5% and 11%, respectively, in the experimental arm, compared with 50% and 30%, respectively, in the control arm.