76TiP Fecal microbiota transplantation to improve efficacy of immune checkpoint inhibitors in metastatic lung cancer

Immunotherapy has recently become a main-stream treatment option in cancer care, with improved clinical outcomes in many malignancies, especially that of lung cancer. The long-term benefits of this treatment however are limited. Thus, there is a critical need to distinguish predictive biomarkers of response from those of resistance, and to develop synergistic strategies for improved therapeutic response. Strong emerging evidence indicates that the gut microbiome has the ability to influence response to immunotherapy. Unlike tumor genomics, the gut microbiome is modifiable, and thus, its modulation to enhance response to immunotherapy is an attractive therapeutic strategy. The main objective of this study is to evaluate the safety and efficacy of Fecal Microbiota Transplant (FMT) in altering response to immunotherapy in patients with metastatic lung cancer. The overall goal is to determine microbiome compositional and gene-content changes in patients who respond more efficiently to immunotherapy subsequent to FMT. This understanding may lead to future microbiome-based treatments combined with immunotherapy to significantly increase the efficacy of lung cancer treatment. In this prospective clinical-and molecular study, we will perform an in-depth analysis of the potential role of FMT in the context of immunotherapy. This prospective, stratified, randomized, placebo-controlled, double-blinded, comparative study. The study will assess the feasibility of Fecal microbiome transplant (FMT) when used in conjunction with standard immunotherapy +/- chemotherapy as a first-line treatment for metastatic lung cancer to enhance the disease control rate. Completely respond metastatic patients to immunotherapy will serve as the fecal implant donors. Patients will start receiving placebo/antibiotics then receive placebo/FMT on the first day of the (chemo-)immunotherapy cycle 1 and then every 3 weeks. The FMT capsules and (chemo-)immunotherapy administrations will be repeated until End of Treatment. NCT05502913. I. Massalha. Israel Cancer Association.