Dr Dizman on Future Efforts to Elucidate Benefit With CBM588 in First-Line RCC

Nazli Dizman, MD, hematology/oncology fellow, The University of Texas MD Anderson Cancer Center, discusses next steps planned for research with CBM588 in patients with renal cell carcinoma (RCC) in the first line.

Results from a pooled analysis evaluating the impact of CBM588 on gut microbiome composition in patients with RCC who received first-line immune checkpoint inhibitors were presented at 

 The analysis showed that adding CBM588 to treatment with immune checkpoint inhibitors did not increase microbiome diversity or improve the richness of the gut microbiome. Despite the lack of increased diversity, CBM588 had notable effects on specific bacterial species associated with positive outcomes in patients treated with immune checkpoint blockade therapies; CBM588 demonstrated an ability to correct gut dysbiosis.

The data, based on a relatively small patient cohort, are supported by preclinical and translational evidence an suggest potential benefits with CBM588 in this patient population, Dizman says. Regarding next steps, researchers are currently conducting further laboratory studies of CBM588 in mice, she details. Additionally, a phase 3 clinical trial is being planned through the SWOG cooperative groups. This trial aims to assess clinical outcomes with the addition of CBM588 to immune checkpoint blockade-based first-line combinations in metastatic RCC, Dizman says.

There is considerable enthusiasm regarding these next steps, Dizman states. The goal of such research is to elucidate the detailed mechanism of action of CBM588 and to determine if it can indeed enhance clinical outcomes, she emphasizes. In the interim, patients are encouraged to participate in ongoing studies exploring lifestyle interventions, biotherapeutics, or fecal microbiota transplants, Dizman says. These approaches have shown strong proof-of-concept evidence and could offer potential benefits, but larger trials are needed to confirm their effectiveness in clinical practice, she concludes.

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Nazli Dizman, MD, discusses next steps planned for research with CBM588 in patients with renal cell carcinoma in the first line.

Dr Dizman on the Impact of CBM588 on the Gut Microbiome in ICI-Treated Patients With RCC

Nazli Dizman, MD, hematology/oncology fellow, The University of Texas MD Anderson Cancer Center, discusses results from a pooled analysis evaluating the impact of CBM588 on gut microbiome composition in patients with renal cell carcinoma (RCC) who received immune checkpoint inhibitors in the first line.

extensively utilized in Japan for various gastrointestinal cancers. Data from 2 randomized phase 1 clinical trials (NCT03829111; NCT05122546) investigating the efficacy of CBM588 revealed improvements in clinical outcomes. This prompted further investigation into the agent's impact on gut microbiome composition in patients with RCC through a pooled analysis of the studies.

The pooled analysis focused on microbiome diversity, a common metric in microbiome research, Dizman begins. Higher microbiome diversity has been linked to better outcomes with immune checkpoint inhibitors in prior studies, she states. However, findings presented at the 

 showed that the addition of CBM588 to checkpoint inhibitors did not result in an increase in diversity or improvement in the richness of the gut microbiome, Dizman reports. Despite the lack of increased diversity, CBM588 showed notable effects on specific bacterial species associated with positive outcomes in patients receiving immune checkpoint blockade therapies, Dizman continues. For instance, 

, which typically declines in the standard of care arm, maintained stable abundance in the CBM588 arm. This suggests that CBM588 supplementation may help preserve beneficial bacterial species that are otherwise reduced during standard treatments, she explains.

Moreover, one of the most significant findings was CBM588’s ability to correct gut dysbiosis, Dizman emphasizes. Dysbiosis, an imbalance in the gut microbiome, is often characterized by a reduced ratio of beneficial bacteria. CBM588 increased the abundance of Bacteroidetes and simultaneously decreased the abundance of Firmicutes, she details. The resulting increase in the Bacteroidetes to Firmicutes ratio indicates a shift towards a more eubiotic, or balanced, gut microbiome, Dizman says. This shift suggests that CBM588 supplementation helps the microbiome evolve in a manner that supports overall health, potentially enhancing the efficacy of immune checkpoint inhibitors, she concludes.

These findings indicate that CBM588 could play a vital role in modulating the gut microbiome to improve clinical outcomes in cancer patients.

Nazli Dizman, MD, discusses the impact of CBM588 on gut microbiome composition in patients with renal cell carcinoma who received immune checkpoint inhibitors in the first line.

Nazli Dizman, MD

Articles

Dr Dizman on Future Efforts to Elucidate Benefit With CBM588 in First-Line RCC

Dr Dizman on the Impact of CBM588 on the Gut Microbiome in ICI-Treated Patients With RCC