CBM588—a live bacterial product—may improve clinical outcomes for patients with metastatic renal cell carcinoma (mRCC) when combined with the tyrosine kinase inhibitor (TKI) cabozantinib plus nivolumab, according to a late-breaking abstract presented at the American Society of Clinical Oncology 2023 Annual Meeting.
Previous research has shown that CBM588 may improve clinical outcomes in patients with mRCC receiving first-line therapy with dual immune checkpoint inhibitors (ICIs). TKIs in combination with ICIs are considered a standard-of-care treatment approach for patients with mRCC.
Hedyeh Ebrahimi, MD, MPH, and colleagues designed an analysis to determine if CBM588 would augment clinical outcomes in patients with mRCC when added to a cabozantinib-plus-nivolumab treatment regimen. A total of 30 patients with histologically verified—clear-cell, papillary, or sarcomatoid component—mRCC and no prior systemic therapy for metastatic disease were included in the study. Patients were randomized (1:2) to receive either cabozantinib plus nivolumab at the standard dose and schedule alone or with CBM588.
The primary end point was the relative abundance of Bifidobacterium spp in stool specimens at baseline and after 12 weeks of treatment. Among the secondary end points were response rate, overall survival, progression-free survival (PFS), systemic immunomodulation, and toxicity.
Researchers noted that 5 patients had sarcomatoid features and 2 patients had predominant papillary histology. Twelve, 12, and 6 patients had good-, intermediate-, and poor-risk disease, respectively.
Metagenomic sequencing of paired stool specimens showed a significant decrease in diversity from baseline to week 12 in patients in the cabozantinib-plus-nivolumab cohort (P=.02), whereas no significant difference was observed in patients in the CBM588 cohort. Additionally, no significant change in Bifidobacterium spp was observed.
The reported response rate was 63% in patients in the CBM588 cohort versus 33% in those receiving cabozantinib plus nivolumab alone. Median PFS was not reached versus 5.8 months, respectively (P=0.3).
Grade 3/4 toxicities were 42% and 44%, respectively.
“In the second prospective trial assessing the addition of CBM588 to ICI-based therapy in mRCC, a consistent result with improved PFS and response rate was observed,” study authors concluded. “Further translational efforts are underway to characterize the mechanism through which CBM588 augments clinical activity.”