Microbiotica progresses melanoma trial
The international trial is due to recruit up to 40 patients at clinical centres in the UK, France, Italy and Spain with initial data readouts expected by the end of 2025.
PD-1 inhibitor immunotherapies have revolutionised cancer treatment and are now commonly used to treat melanoma. However, new treatment options are still needed to extend the benefit to patients for whom immunotherapies do not work (treatment-resistant patients). This can be up to 50 per cent of all advanced melanoma patients.
The MELODY-1 study will investigate the safety, tolerability, and initial signals of efficacy of MB097 in advanced (metastatic) melanoma, in combination with KEYTRUDA® (pembrolizumab), MSD's (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy, in patients with cutaneous melanoma who have failed to respond to immunotherapies.
MB097 is a once daily, orally administered LBP consisting of a defined consortium of nine strains of commensal bacteria designed to enhance the efficacy of immune checkpoint inhibitors (ICIs). The bacterial strains in MB097 were identified by analysing the microbiome of patients in multiple studies of ICIs in melanoma, including the MELRESIST study carried out with the company’s collaborators at Cambridge University Hospitals, UK.
Collectively, the MB097 bacterial consortium provides microbiome signalling that appears to be needed for ICI response. Pre-clinical studies demonstrate that MB097 activates core pathways of the immune system including Cytotoxic T Lymphocytes and Natural Killer cells to enable them to kill tumour cells.
Research to understand the mechanism of action of the nine bacterial strains has indicated that in addition to this immune-activating effect, the bacteria in MB097 produce metabolites that act directly at the site of the tumour.
All patients in this Phase 1b, first-in-human, randomised open-label clinical trial will receive MB097 and pembrolizumab for up to six months. Half of the participants will also receive vancomycin before starting the co-therapy to determine whether it helps the bacterial strains in MB097 embed and grow in the gut more efficiently.
As well as assessing the safety and tolerability of the co-therapy, the trial will measure standard oncology treatment efficacy including imaging measurements of tumour response. In addition, it will measure the engraftment of the strains being dosed, and changes in several immune biomarkers.
Microbiotica’s Chief Medical Officer, Ron Carter said: “The gut microbiome, the community of bacteria in the gut, plays a crucial role in digesting food and protecting people from infections, but it also interacts very closely with the immune system.
“In cancer patients, the bacteria in MB097 appear to be associated with better response rates to immune checkpoint inhibitor therapies, such as anti PD-1 drugs. MB097, with its precisely selected microbes based on data from responsive patients, in combination with ICIs, could therefore activate a therapeutic benefit for non-responding patients with advanced melanoma.
“Moreover, as the MB097 bacteria are found in healthy subjects as well as in patients who responded to ICIs, we anticipate a favourable safety profile.”
Professor Paolo A. Ascierto, Director of the Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, National Tumor Institute Fondazione G. Pascale, Naples, Italy, where the first patient has been dosed, added: “With more than half of patients with melanoma being treated with anti PD-1 drugs either not responding or relapsing, I have great hope that the addition of a MB097 precision microbiome therapy such to the treatment regime can improve the outcome for many more patients.”
Microbiotica, based in purpose-built facilities at Chesterford Research Park near Cambridge, has raised more than £62 million equity investment, including a £50m Series B in 2022, with venture investors including British Patient Capital, Cambridge Innovation Capital, Flerie Invest, IP Group plc, Seventure Partners and Tencent. The company has also received financial support from the US-based Crohn’s and Colitis Foundation.