City of Hope researchers report that gut microbiome composition may influence how patients respond to immunotherapy combinations in metastatic renal cell carcinoma, pointing to a potential biomarker that could help guide treatment selection in the future.
The microbiome is a rising focus at City of Hope, highlighted by a recent symposium that convened federal health leaders and top cancer centers to accelerate progress in the field.
The study findings come from a combined analysis of two randomized phase 1 trials evaluating standard-of-care immune checkpoint inhibitor regimens with or without the addition of CBM5881, a live biotherapeutic designed to modulate the gut microbiome. The trials enrolled treatment-naïve patients with metastatic disease who received either nivolumab plus ipilimumab or nivolumab plus cabozantinib, reflecting commonly used immunotherapy-based frontline options.
Across the combined dataset, patients who received CBM588 in addition to immunotherapy achieved an objective response rate of 66.7%, compared with 20% among those receiving standard therapy alone. Median progression-free survival improved to 32.1 months with the combination versus 3.7 months with standard treatment.
Gut imbalance
Researchers also used a metagenomic measure called TOPOSCORE to assess gut imbalance and found that patients with a more disrupted microbiome saw the greatest benefit. In this subgroup, progression-free survival increased from 2.8 months to 24.9 months with the addition of CBM588. The association between microbiome profile and treatment response was particularly evident in patients who received nivolumab plus ipilimumab, suggesting that the microbiome may interact differently depending on the immunotherapy backbone.
The new data support a growing body of research linking the gut microbiome to immune response.
“These findings suggest the microbiome may play a direct role in shaping immunotherapy outcomes,” said Rahul Winayak, M.D., postdoctoral fellow at City of Hope. “If validated in larger studies, this approach could help guide treatment decisions and improve outcomes for patients with kidney cancer.”
A randomized phase 3 trial is underway to further evaluate this strategy.
The findings
The findings will be presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, where the cancer center will showcase 49 abstracts spanning solid tumors and blood cancers.
This year’s research, to be presented in Chicago from May 29 to June 2, reflects growing efforts to tailor cancer treatment based on tumor biology, prior therapies and patient-specific factors that influence response.
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