Commentary
Video
Author(s):
Nazli Dizman, MD, explains the rationale for evaluating the impact of CBM588 on the gut microbiome in patients with metastatic RCC.
“[CBM588] has some preclinical data suggesting that it may improve gastrointestinal [GI] barrier function, especially under the conditions of antibiotic-induced dysbiosis.”
Nazli Dizman, MD, hematology/oncology fellow, The University of Texas MD Anderson Cancer Center, explains the rationale for evaluating CBM588 and its impact on gut microbiome in patients with metastatic renal cell carcinoma (RCC) treated with immune checkpoint inhibitors.
CBM588 is a live bacterial product that has been used in Japan for gastrointestinal (GI) conditions for decades, according to Dizman. She notes that preclinical data have shown that CBM588 may improve GI barrier function, particularly with antibiotic-induced dysbiosis.
Findings from previous preclinical data also suggest that CBM588 improves the amount of present good bacteria in the gut microbiome, Dizman adds. In 2 randomized phase 1 studies (NCT03829111; NCT05122546), she states that the agent was assessed and demonstrated improved clinical outcomes.
In both studies, Dizman and her colleagues analyzed stool samples from enrolled patients with metastatic RCC who were treated with either standard-of-care (SOC) nivolumab (Opdivo) plus ipilimumab (Yervoy) with or without CBM588, or SOC cabozantinib (Cabometyx) plus nivolumab with or without CBM588.
Gut microbiome diversity and composition at baseline were compared, and at week 12 among patients in the SOC are arms vs those who received CBM588 plus a SOC regimen. In the analysis, 59 patients were included, of which 39 received CBM588 plus SOC as first-line treatment. Data demonstrated that in both the SOC and CBM588/SOC cohorts, there were no statistically significant differences among alpha and beta diversity between baseline and week 12.
Going forward, Dizman and colleagues plan to further explore the effect of CBM588 on the composition of the gut microbiome, she concludes. A phase 3 study evaluating the addition of the agent to a SOC immune checkpoint inhibitor combination is being planned.