MaaT Pharma has randomized the first patient in the IMMUNOLIFE Phase 2 clinical study, which is exploring whether modulation of the gut microbiome can help overcome resistance to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer (NSCLC).

IMMUNOLIFE is a randomized, multicentre exploratory trial sponsored by Gustave Roussy and conducted within the IMMUNOLIFE consortium. The study is evaluating the potential of MaaT033, an oral pooled microbiotherapy, in combination with cemiplimab, compared with best investigator choice in patients with advanced NSCLC who have developed resistance to PD-1 or PD-L1 inhibitors following antibiotic exposure and who present with antibiotic-induced gut dysbiosis.

The trial is based on growing evidence that disruption of the gut microbiome may negatively influence response to immunotherapy. Antibiotic exposure has been increasingly associated with reduced efficacy of immune checkpoint inhibitors, particularly in lung cancer, where treatment resistance remains a major clinical challenge.

IMMUNOLIFE is enrolling 162 patients across 14 centres in France. Patients are randomized 1:1 to receive either MaaT033 orally for one week prior to each cycle of cemiplimab, administered every three weeks for six months and followed by cemiplimab alone, or best investigator choice as second-line therapy. The primary endpoint is disease control rate at 12 weeks. Patient enrolment is expected to take approximately two years, with total treatment duration of up to two years.

Lisa Derosa, coordinating investigator of the IMMUNOLIFE trial at Gustave Roussy, said: “Gut dysbiosis is increasingly recognized as a risk factor for immunoresistance to immunotherapy. MaaT033 is designed to restore microbiome balance and may help improve patients’ response to treatment.”

The study is designed to assess the clinical rationale for combining a full-ecosystem microbiotherapy with immune checkpoint inhibition in a defined population of patients presenting antibiotic-induced dysbiosis. An interim futility analysis is planned for the first half of 2027, following randomization of the 81st patient. Primary results after one year of follow-up post-treatment could be expected in late 2030.

According to MaaT Pharma, the IMMUNOLIFE trial builds on data generated in its hemato-oncology programmes, where complex donor-derived microbiome products have been evaluated for their ability to restore immune homeostasis in patients with pre-existing dysbiosis.

Hervé Affagard, chief executive officer and co-founder of MaaT Pharma, said: “We have built substantial evidence in our hemato-oncology programs that complex donor-derived products restore immune homeostasis in the context of pre-existing dysbiosis. This study represents an opportunity to further explore these findings in immuno-oncology in a well-defined patient population expected to show antibiotic-mediated dysbiosis.”

IMMUNOLIFE forms part of the company’s broader exploratory strategy launched in 2022, which also includes the PICASSO Phase 2a randomized controlled trial sponsored by AP-HP in Paris. PICASSO is evaluating MaaT013 in combination with immune checkpoint inhibitors in patients with metastatic melanoma. MaaT Pharma said it has been informed by the academic sponsor that topline results from PICASSO are now expected in the first half of 2026, rather than late 2025 as previously indicated.

Data generated from IMMUNOLIFE and PICASSO are expected to inform the clinical development strategy for MaaT034, the company’s next-generation microbiome-based therapy, as well as contribute to its microbiome-informed AI platform.

The IMMUNOLIFE consortium brings together academic institutions including Gustave Roussy, INSERM, Paris Saclay University, INRAe and the Hospital-University Institute Méditerranée Infection, alongside biotech partners. The consortium is funded by the French National Research Agency and aims to address primary resistance to immune checkpoint inhibitors in advanced NSCLC following antibiotic exposure.