A recent analysis of phase 1 clinical trials suggests that CBM588, an experimental biotherapeutic, may improve clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitors (ICIs). The findings, presented at the 2024 Kidney Cancer Research Summit (KCRS), highlight CBM588's potential to modulate the gut microbiome and enhance response to ICI therapy.
The pooled analysis included data from two studies: one evaluating nivolumab plus ipilimumab with CBM588 (NCT03829111) and another assessing nivolumab plus cabozantinib with CBM588 (NCT05122546). These trials involved a total of 39 patients who received standard-of-care (SOC) therapy in combination with CBM588 and 20 patients who received SOC alone. Researchers analyzed stool samples to assess gut biome diversity and composition at baseline and after 12 weeks of treatment.
Impact on Gut Microbiome
The results indicated that treatment with CBM588 was associated with a notable correction of gut dysbiosis and prevention of the depletion of ICI response-associated species. This suggests a plausible mechanism by which CBM588 could enhance clinical outcomes in mRCC patients undergoing ICI therapy. According to Dr. Nazli Dizman, a hematology/oncology fellow at The University of Texas MD Anderson Cancer Center, these findings are promising and warrant further investigation.
Future Directions and Phase 3 Trial
Dr. Dizman expressed optimism about future research directions, stating, "I am optimistic that we will hopefully find the details of the mechanism of action [of CBM588]. I’m hoping that we would observe improvements in clinical outcomes once the phase 3 trial is completed." A planned phase 3 trial will evaluate the clinical activity and gut microbiome modulation capacity of CBM588 combined with ICIs in patients with metastatic RCC receiving frontline ICI combinations.
Encouraging Patient Interventions
In addition to CBM588, Dr. Dizman encouraged patients to consider other interventions with strong proof-of-concept evidence, including lifestyle interventions, alternative biotherapeutics, and fecal microbiota transplant (FMT), to potentially improve their outcomes. She emphasized the importance of participating in studies that explore these approaches to enhance patient outcomes in the future.
