IPH5201 + durvalumab

IPH5201 + durvalumab is a combination therapy being investigated for the treatment of non-small cell lung cancer (NSCLC). This combination pairs IPH5201, an anti-CD39 blocking monoclonal antibody, with durvalumab, an anti-PD-L1 monoclonal antibody marketed as Imfinzi[1][7]. ## Mechanism of Action The combination works through complementary immune-modulating mechanisms: - **IPH5201** targets the CD39 immunosuppressive pathway. CD39 is an extracellular membrane-bound enzyme expressed on tumor infiltrating immune cells and stromal cells in several cancer types. By blocking CD39, IPH5201 promotes the accumulation of immunostimulatory adenosine triphosphate (ATP) and prevents the production of immunosuppressive adenosine, potentially boosting anti-tumor activity[3]. - **Durvalumab** (Imfinzi) is an established anti-PD-L1 therapy that works by blocking the interaction between PD-L1 and the PD-1 receptor, preventing tumor cells from evading immune detection[1][7]. ## Clinical Development The combination is currently being evaluated in: 1. **MATISSE Trial (Phase 2)**: A multicenter, single-arm study (NCT05742607) evaluating neoadjuvant and adjuvant treatment with IPH5201 + durvalumab and chemotherapy in treatment-naïve patients with resectable early-stage (stage II to IIIA) non-small cell lung cancer. The first patient was dosed in June 2023[1][7]. - Primary objectives: Assess antitumor activity based on pathological complete response (pCR) and safety - The study is sponsored by Innate Pharma, with AstraZeneca supplying the clinical trial drugs[1][7] 2. **Phase 1 Trial**: Previously, a Phase 1 clinical trial evaluated IPH5201 as monotherapy and in combination with durvalumab with or without oleclumab (anti-CD73 monoclonal antibody) in adult patients with advanced solid tumors. The first patient was dosed in March 2020[6].