UH Seidman Cancer Center researchers to test a gut microbiome intervention as part of a cancer therapy regimen

The S2419 BioFront study is chaired by UH Seidman Cancer Center medical oncologist and Miggo Family Chair in Cancer Research, Pedro Barata, MD, M.Sc, whose work developing the trial was supported in part by a 2023 Coltman Fellowship from The Hope Foundation for Cancer Research.

• Phase III clinical trial will test a gut microbiome intervention as part of a kidney cancer therapy regimen
• The investigational agent is a once-daily capsule requiring no refrigeration or special handling
• Study chaired by UH Seidman Cancer Center medical oncologist and Miggo Family Chair in Cancer Research, Pedro Barata, MD, M.Sc
• S2419 BioFront study funded by SWOG Cancer Research Network

CLEVELAND- University Hospitals Seidman Cancer Center researchers announce the S2419 BioFront study, which is the first SWOG trial and first phase III anywhere to test a gut microbiome intervention as part of a cancer therapy regimen.

The S2419 BioFront study is chaired by UH Seidman Cancer Center medical oncologist and Miggo Family Chair in Cancer Research, Pedro Barata, MD, M.Sc, whose work developing the trial was supported in part by a 2023 Coltman Fellowship from The Hope Foundation for Cancer Research.

The intervention being tested in this potential FDA registration trial is a capsule containing a strain of the bacterium Clostridium butyricum known as CBM588. Early phase studies in renal cell carcinoma showed that the combination of CBM588 with immunotherapy have produced encouraging signals in survival outcomes and response rates, with no evidence of additional toxicity.

"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. 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," said Dr. Barata.

S2419 will enroll more than 700 patients with advanced renal cell carcinoma with a clear cell component. All will get a standard-of-care immunotherapy-based treatment, chosen in consultation with their physician. Once that regimen has been selected, they'll be randomized to also get either a placebo or the CBM588 capsule.

The primary endpoint is progression-free survival, with secondary endpoints that include response rates and overall survival. The study team will also compare toxicities between the arms and potential interactions with other medications patients are taking.

A set of quality-of-life objectives will focus on gastrointestinal symptoms and the association of clinical and other outcomes with patient-reported dietary fiber intake.

To confirm the safety of pairing CBM588 with immunotherapy-based treatment combinations, S2419 will run with a safety run-in, with three months of enhanced toxicity monitoring for the first 50 randomized patients.

The investigational agent is a once-daily capsule requiring no refrigeration or special handling.

The clinical trial is funded by SWOG Cancer Research Network. A major, publicly funded international cancer research organization founded in 1956. As a part of the National Cancer Institute's (NCI) National Clinical Trials Network (NCTN), it conducts Phase II and III trials for adult cancers, involving over 12,000 members across 1,000+ global institutions. SWOG has led to FDA approval for 15 therapies and changed over 100 care standards.