Phase 3 trial to evaluate gut microbiome intervention in renal cell carcinoma

A phase 3 randomized trial will evaluate whether modulation of the gut microbiome can improve outcomes in patients with advanced clear cell renal cell carcinoma (ccRCC) receiving standard-of-care immunotherapy-based regimens. The BioFront study (NCT07383441; S2419), led by the SWOG Cancer Research Network, is testing the addition of the investigational live biotherapeutic CBM588 to frontline immune checkpoint inhibitor (ICI)-based therapy in these patients.

The study represents the first phase 3 study to prospectively test a microbiome-directed intervention in combination with systemic cancer therapy.

“The phase 3 study, BioFront, represents an important step toward understanding how the gut microbiome can be leveraged to improve outcomes for patients with advanced kidney cancer,” Pedro C. Barata, MD, MSc, FACP, study chair and a medical oncologist at University Hospitals Seidman Cancer Center in Cleveland, Ohio, said in a news release.¹ “By integrating a novel, well-tolerated intervention with standard immunotherapy, we aim to generate high-level evidence that could meaningfully improve outcomes of patients and inform future treatment strategies.”

CBM588 is an investigational live biotherapy and a strain of the bacterium Clostridium butyricum. The agent is delivered in a once-daily capsule and does not require refrigeration or special handling. Early-phase studies in RCC have suggested that combining CBM588 with ICIs may improve response rates and survival outcomes without increasing toxicity. The BioFront trial is designed to provide confirmatory evidence in a larger, randomized setting.

In total, the study is designed to enroll more than 700 patients with advanced or metastatic ccRCC containing a clear cell component. To be eligible for enrollment, patients must have a Zubrod performance status of 0 to 2 within 28 days of registration as well as adequate levels of hemoglobin, leukocytes, absolute neutrophil counts, platelets, and total bilirubin.²

Patients are assigned to standard-of-care (SOC) ICI-based regimens selected by treating physicians based on disease risk and clinical factors, and then randomly assigned to receive either CBM588 or placebo in a double-blind fashion. SOC regimens permitted in the study include combinations widely used in frontline RCC management, such as nivolumab (Opdivo) plus ipilimumab (Yervoy), pembrolizumab (Keytruda) plus axitinib (Inlyta), nivolumab plus cabozantinib (Cabometyx), and pembrolizumab plus lenvatinib (Lenvima). The investigational agent is administered orally in 42-day cycles alongside these therapies. All patients will undergo CT or MRI and blood sample collection throughout the study.

The primary end point is investigator-assessed progression-free survival, evaluated up to 5 years. Secondary end points include overall survival and safety outcomes. Additional analyses will evaluate time to subsequent systemic therapy, the impact of concomitant medications (eg, antibiotics, proton pump inhibitors, steroids), and quality-of-life objectives with a focus on gastrointestinal symptoms and the association between clinical outcomes and patient-reported dietary fiber intake.

To confirm the safety of pairing CBM588 with immunotherapy-based combinations, the trial includes a safety run-in phase for the first 50 randomly assigned patients, with enhanced toxicity monitoring during the initial treatment period.

REFERENCES

1. Denholm J. UH Seidman Cancer Center researchers to test a gut microbiome intervention as part of a cancer therapy regimen. News release. University Hospitals. April 7, 2026. Accessed April 9, 2026. https://news.uhhospitals.org/news-releases/articles/2026/04/uh-seidman-cancer-center-researchers-to-test-a-gut-microbiome-intervention

2. Adding biotherapy or placebo to standard treatment for advanced kidney cancer. ClinicalTrials.gov. Updated February 3, 2026. Accessed April 9, 2026. https://clinicaltrials.gov/study/NCT07383441