MEDI5395 + durvalumab

MEDI5395 + durvalumab is a combination therapy that has been investigated in a Phase I clinical trial for patients with advanced solid tumors. This combination represents an innovative approach to cancer immunotherapy, combining an oncolytic virus with an immune checkpoint inhibitor. ## Drug Components MEDI5395 is a recombinant attenuated Newcastle disease virus (NDV) engineered to express human granulocyte-macrophage colony-stimulating factor (GM-CSF). This oncolytic virus selectively infects and destroys cancer cells while sparing normal cells. The GM-CSF transgene helps stimulate the immune system to recognize and attack cancer cells[1][3]. Durvalumab is an established anti-PD-L1 immune checkpoint inhibitor that is already approved for the treatment of various solid tumors. It works by blocking the interaction between PD-L1 on tumor cells and PD-1 on immune cells, thereby preventing the tumor from evading immune surveillance[1][3]. ## Clinical Development The first-in-human Phase I study of this combination was conducted in patients with advanced solid tumors who had relapsed or were refractory or intolerant to at least one prior line of standard treatment. The study assessed four dose levels of MEDI5395 (10^8^, 10^9^, 10^10^, 10^11^ focus forming units) with either sequential or delayed durvalumab administration[1][3]. In this trial, MEDI5395 was administered intravenously as six doses over 15-18 days, while durvalumab was given at a dose of 1500 mg intravenously every 4 weeks for up to 2 years[1][5]. ## Efficacy and Safety Results The study demonstrated preliminary efficacy with an overall response rate of 10.3% (4/39 patients) and a disease control rate of 30.8% (12/39 patients). Four patients achieved partial responses, including patients with non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC). Notably, three of these four patients had previously received anti-PD-1 immune checkpoint inhibitors[3]. Regarding safety, all 39 patients experienced at least one treatment-emergent adverse event. Two patients experienced dose-limiting toxicities: one with Grade 3 fatigue and another with Grade 3 neutropenia. The maximum tolerated dose of MEDI5395 at the time of study termination was 10^11^ FFU (with 2 log desensitization for the first dose) with sequential durvalumab, and 10^10^ FFU (with 1 log desensitization for the first dose) with delayed durvalumab[3]. The study concluded that this combination demonstrated feasibility, safety, and preliminary efficacy in patients with advanced solid tumors, suggesting potential for further development in cancer immunotherapy[1][3].