S2419 BioFront: Going for the Gut

We’re just weeks from opening an innovative kidney cancer trial that has the potential to significantly expand how we think about cancer therapeutics – the S2419 BioFront trial.

It’s the first SWOG trial – and the first phase III trial anywhere – to test a gut microbiome intervention as part of a cancer therapy regimen. If positive, it could support a Food and Drug Administration (FDA) registration strategy. 

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 that combined CBM588 with immunotherapy have produced encouraging signals in survival outcomes and response rates, with no evidence of additional toxicity. 

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 open with a safety run-in, with three months of enhanced toxicity monitoring for the first 50 randomized patients.

The S2419 BioFront study is chaired by Dr. Pedro Barata, whose work developing the trial was supported in part by a 2023 Coltman Fellowship from The Hope Foundation for Cancer Research. Dr. Barata further refined the study in our Early-Stage/Young Investigator Training Course – now our LEAP-D program.  

His BioFront study co-chairs are alumni of the same program – Drs. Ulka Vaishampayan and Sumanta Pal. 

Lead biostatistician on the trial is Dr. Cathy Tangen, and the patient advocate is Laura Esfeller.

Drs. David McConkey and Nazli Dizman are translational medicine co-chairs, and Dr. Cristiane Bergerot is co-chair for quality-of-life objectives.

Finally, more and more of our trials are integrating a co-chair for community engagement (we hope that number continues to grow). BioFront’s co-chair for community engagement is Dr. Helen Moon.  

The study was designed to be feasible across the full spectrum of SWOG member sites, including academic institutions, community practices, and VA medical centers. The investigational agent is a once-daily capsule requiring no refrigeration or special handling. 

Immune checkpoint inhibitors (ICIs) have transformed outcomes across a range of cancers. If BioFront demonstrates that modulating the gut microbiome can enhance ICI efficacy in RCC, the results may open a door to augmenting ICIs’ benefits in other malignancies as well through biologically informed intervention.

With a target activation date of April 1st (no fooling), we look for S2419 BioFront to be open for business before our spring group meeting (note though meeting registration will open February 24th). 
 

S2419, Phase III Double Blinded Trial of Immune-Based Therapy with a Live Biotherapeutic CBM588 or Placebo for Frontline Therapy of Advanced Clear Cell Renal Cell Carcinoma (BioFront Trial)