Microbiotica Doses First Patient in Phase 1b Trial of MB097 Microbiome Therapy for Advanced Melanoma
核心洞察
Microbiotica (搜索) has dosed the first patient in its international MELODY-1 Phase 1b trial testing MB097, a precision microbiome therapy, in combination with pembrolizumab for advanced melanoma (搜索) patients who failed to respond to immunotherapies.
The oral live biotherapeutic product contains nine bacterial strains designed to enhance immune checkpoint inhibitor efficacy, potentially benefiting up to 50% of advanced melanoma (搜索) patients who are treatment-resistant.
The randomized trial will recruit up to 40 patients across the UK, France, Italy, and Spain, with initial data readouts expected by the end of 2025.
Microbiotica (搜索) has achieved a significant milestone by dosing the first patient in its international Phase 1b MELODY-1 trial, testing the precision microbiome therapy MB097 in combination with MSD's pembrolizumab (KEYTRUDA®) for advanced melanoma (搜索) patients who have failed to respond to immunotherapies. The Cambridge-based clinical-stage biopharma company announced that up to 50% of all advanced melanoma patients could potentially benefit from this novel approach.
Novel Microbiome-Based Approach to Cancer Treatment
MB097 represents a once-daily, orally administered live biotherapeutic product consisting of nine precisely selected bacterial strains designed to enhance the efficacy of immune checkpoint inhibitors. The bacterial consortium was identified through comprehensive microbiome analysis of patients in multiple ICI studies in melanoma, including the MELRESIST study conducted with collaborators at Cambridge University Hospitals (搜索).
"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," explained Ron Carter, Microbiotica (搜索)'s Chief Medical Officer. "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 (搜索) drugs."
Trial Design and Patient Population
The MELODY-1 study is a Phase 1b, first-in-human, randomized open-label clinical trial that will recruit up to 40 patients at clinical centers across the UK, France, Italy, Spain, and up to 18 sites total. All participants will receive MB097 and pembrolizumab for up to six months, with half also receiving vancomycin before starting co-therapy to determine whether it helps the bacterial strains embed and grow in the gut more efficiently.
Patients benefiting from treatment at the end of the initial six-month period may continue receiving pembrolizumab for up to an additional 18 months, totaling approximately 24 months of treatment. The trial targets patients with cutaneous melanoma (搜索) who have failed to respond to immunotherapies, addressing a critical unmet medical need in advanced melanoma (搜索) treatment.
Mechanism of Action and Preclinical Evidence
Preclinical studies demonstrate that MB097 activates core immune system pathways, including cytotoxic T lymphocytes (搜索) and natural killer cells (搜索), enabling them to kill tumor cells more effectively. Research into the mechanism of action has revealed that beyond immune activation, the bacteria in MB097 produce metabolites that act directly at tumor sites.
"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 (搜索)," Carter noted. "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."
Clinical Significance and Expert Perspectives
Professor Paolo A. Ascierto, Director of the Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics at National Tumor Institute Fondazione G. Pascale (搜索) in Naples, Italy, where the first patient was dosed, emphasized the potential paradigm shift this approach represents. "Combining beneficial microbes with immune checkpoint inhibitors to increase the number of patients who could benefit from these life-saving therapies is a cutting-edge modality that could change the medical paradigm for advanced melanoma (搜索) patients," he said.
Pippa Corrie, PhD, FRCP, Affiliated Associate Professor of Medical Oncology at the University of Cambridge and leader of the UK arm of the study, highlighted the scientific foundation underlying MB097. "Our MELRESIST study has been fundamental in identifying precisely those gut bacteria that are associated with positive outcomes for melanoma patients on ICIs. The microbial signature comprising a small group of bacteria that were consistently raised in abundance in responding patients across multiple independent cohorts, which gives confidence that MB097 has real potential."
Trial Endpoints and Timeline
The study will assess safety and tolerability of the co-therapy while measuring standard oncology treatment efficacy through imaging measurements of tumor response. Additionally, researchers will monitor the engraftment of the dosed bacterial strains and changes in several immune biomarkers. Initial data readouts are expected by the end of 2025.
The trial operates under study identifiers NCT06540391, MSD KEYNOTE-E75, and 023-507377-17, with MSD supplying KEYTRUDA for the combination therapy evaluation. This collaboration represents a significant step forward in exploring the intersection of microbiome science and cancer immunotherapy, potentially offering new hope for patients with treatment-resistant advanced melanoma (搜索).