Adding the probiotic CBM588 to cabozantinib/nivolumab in patients with metastatic RCC improved response rate and progression-free survival in a phase 1 trial.
Hedyeh Ebrahimi, MD
The combination of cabozantinib and nivolumab is a standard first-line systemic treatment for metastatic clear cell renal cell carcinoma (RCC). Both retrospective and prospective clinical data suggest that CBM588, an orally available liver bacterial product containing a specific strain of Clostridium butyricum, can improve the response to immune checkpoint blockade in patients with cancer. To explore the effect of CBM588 on standard first-line therapy in patients with metastatic RCC, a phase 1 trial (NCT05122546) was performed. Hedyeh Ebrahimi, MD, presented the results at the 2023 ASCO Annual Meeting, held June 2-6 in Chicago.
A total of 30 patients were randomly assigned 2:1 to receive either cabozantinib/nivolumab/CBM588 or cabozantinib/nivolumab. CBM588 (80 mg) was administered twice daily. The primary endpoint of the study was change in Bifidobacterium species from baseline to week 12. Secondary endpoints were progression-free survival (PFS), response rate, and toxicity.
No statistically significant difference was observed in the relative abundance of Bifidobacterium species between baseline and week 12 in the control arm or experimental arm. Also, no statistically significant difference was observed in the alpha diversity between the control arm and experimental arm, both at baseline and at week 12. Therefore, the study did not meet its endpoint.
The median PFS, a secondary endpoint, was significantly improved in the experimental arm compared with the control arm: not reached versus 5.8 months (P=0.042). In addition, the response rate was improved in the experimental arm (56 vs 25%). No difference in toxicity was observed between the study arms.
Based on these results, Dr. Ebrahimi concluded that “the addition of CBM588 to cabozantinib/nivolumab was not associated with significant changes in the gut microbiome. However, CBM588 improved both response rate and PFS of cabozantinib/nivolumab treatment in metastatic RCC. This is in line with previous clinical data.”
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