City of Hope: Gut Microbiome Changes Aid Metastatic Kidney Cancer Outcomes

Researchers at City of Hope, one of the largest cancer research and treatment organizations in the United States, have discovered a promising new use for a live biotherapeutic product called CBM588 in treating metastatic kidney cancer. Their findings, published in Nature Medicine, indicate that patients who took CBM588 in combination with immunotherapy and tyrosine kinase inhibitors experienced better health outcomes. This phase 1 trial represents a significant step forward in cancer treatment, suggesting that CBM588 can modulate the gut microbiome to enhance the effectiveness of cancer immunotherapies approved by the Food and Drug Administration.

City of Hope scientists are now collaborating with the SWOG Cancer Research Network to plan a global phase 2/3 trial to further evaluate the efficacy of CBM588 in advanced cancer treatment. Sumanta Pal, M.D., a professor and vice chair at City of Hope’s Department of Medical Oncology & Therapeutics Research, is expected to co-lead this trial. According to Dr. Pal, City of Hope is pioneering in demonstrating that a live bacterial product can improve clinical outcomes for kidney cancer patients undergoing immunotherapy. The potential of CBM588 to enhance immune checkpoint inhibitor-based treatments, improve patient outcomes, and modulate the gut microbiota is particularly exciting. Further clinical trials are essential to confirm these benefits and address current challenges.

In the phase 1 trial, 30 patients with metastatic kidney cancer were randomized to receive cabozantinib, a vascular endothelial growth factor receptor inhibitor, alongside nivolumab, a targeted immunotherapy, with or without CBM588 as their first-line treatment. Participants’ gut microbiomes were analyzed initially and 13 weeks into treatment through stool samples. The study found increased levels of unclassified Ruminococcaceae genera, which has been associated with better clinical outcomes in patients treated with immune checkpoint inhibitors. The bacterium in CBM588, Clostridium butyricum MIYAIRI 588, produces butyric acid, an important compound for intestinal health and immune modulation.

City of Hope has granted an exclusive worldwide license to Osel for the intellectual property around using CBM588 to enhance the effectiveness of checkpoint inhibitors for treating cancers, including metastatic renal cell carcinoma. The trial also saw collaboration from scientists at Osel and Miyarisan Pharmaceutical Co. Ltd, the manufacturer of CBM588.

Previous research has shown that the gut microbiome’s composition could predict immunotherapy outcomes for patients with various cancers, including lung cancer, melanoma, and metastatic kidney cancer. Current guidelines for treating metastatic renal cell carcinoma recommend using either dual checkpoint inhibitor therapy or a combination of immunotherapy and tyrosine kinase inhibitors. However, most patients eventually experience disease progression, and subsequent treatments are mainly palliative. Therefore, physicians and scientists are exploring new treatment strategies, such as microbiome modulation, which do not introduce toxic side effects.

“While microbiome modulation is not yet part of standard cancer treatment protocols, it shows great promise in enhancing the efficacy of cancer therapies, particularly immunotherapies,” said Hedyeh Ebrahimi, M.D., M.P.H., a postdoctoral medical oncology fellow at City of Hope and the study’s first author. The growing body of evidence suggests that microbiome-based interventions could soon become a valuable component of cancer treatment strategies.

City of Hope is accelerating its research into the connection between a healthy gut and the success of immune therapies like CAR T cell therapy. This enhanced microbiome program spans basic to clinical research, including studying the gut microbiome’s role in protecting transplant patients from complications during recovery. According to Marcel van den Brink, M.D., Ph.D., president of City of Hope Los Angeles and City of Hope National Medical Center, this study highlights the important role of the microbiome in the efficacy and toxicity of cancer immunotherapy and its potential as a target to improve outcomes.