City of Hope, a US cancer research and treatment organization, and Osel, a California based company developing LBPs for diseases linked to the disruption of the human microbiome, said Phase 1 trial data showed the use of bacterial strain, Clostridium butyricum MIYAIRI 588 (CBM588), in combination with nivolumab/ipilimumab “significantly improved” progression-free survival in patients with metastatic kidney cancer when compared to use of the immunotherapy drugs alone.
“These results can help improve treatment options for patients with kidney cancer and is an important foundational step to bring about more effective targeted therapies for cancer treatment,” said Sumanta K Pal, a professor in the Department of Medical Oncology and Therapeutics Research at City of Hope and senior author of the study.
Last summer, City of Hope granted an exclusive worldwide license to Osel for IP on the use of CBM588 to enhance efficacy of checkpoint inhibitors to treat cancer, including metastatic renal cell carcinoma.
In the clinical trial, 30 patients with metastatic kidney cancer (renal cell carcinoma) who had never received treatment before were randomized to receive either CBM588 orally in combination with nivolumab/ipilimumab or nivolumab/ipilimumab alone.
Data showed a significant improvement in progression-free survival in patients treated with CBM588 plus nivolumab/ipilimumab (12.7 months) compared to nivolumab/ipilimumab alone (2.5 months). Additionally, use of CBM588 in combination therapy was linked to an increase in response rate when compared to use of nivolumab/ipilimumab therapy alone (58% vs. 20%), said the authors.
“Over the last several years, the immunotherapy field has been closely studying how the GI microbiome can enhance immune checkpoint efficacy for the treatment of cancer,” said Thomas Parks, director of product development at Osel. “Compared to microbiome modulation using fecal transplants, CBM588 given orally is potentially a more effective, reproducible, scalable and safer method to treat patients.”
Osel licensed the rights for the pharmaceutical use of CBM588 in the US, Canada and Europe from Japan's Miyarisan Pharmaceutical Co Ltd.
“City of Hope is currently conducting another Phase 1 clinical trial of CBM588 in combination with nivolumab and tyrosine kinase inhibitor, cabozantinib, for the treatment of advanced or metastatic kidney cancer,” said Pal. “We are working to open a large, randomized Phase 3 trial of CBM588 in the future.”
Jeffrey Trent, president of City of Hope affiliate, Translational Genomics Research Institute (TGen) and a contributor to the study, commented how the field of microbiome research is exploding as evidenced. “This study points to the continued growth of clinical research and scientific understanding of the microbiome’s connection to disease and recovery.”
Reigniting the immune system
NASDAQ-listed LBP developer, 4D Pharma, is also active in the oncology field, and has ongoing partnerships with leading industry players in relation to its single LBP strain, MRx0518.
“What we are demonstrating is that MRx0518 has this really unique property to enhance the innate and adaptive immune system and increase tumor infiltrating lymphocytes (TILs), to stimulate systemic proinflammatory cytokines and chemokines, and upregulate a number of the biological pathways that are associated with an anti-tumor response.
“We have seen that in the Keytruda (MSD’s immune checkpoint inhibitor immunotherapy) setting, where patients have pretty much failed everything else, they have had a checkpoint inhibitor, they have stopped responding to that, and what we are able to do is reignite the immune system, to help the checkpoint inhibitor be more effective,” Duncan Peyton, CEO, 4D Pharma, told this publication last year.