Multicenter first-in-human phase 1 study of MEDI1191 plus durvalumab in patients with advanced solid tumors

MEDI1191 is a lipid nanopraticle-formulated mRNA designed to induce local interleukin-12 production and intensify antitumor T cell responses. A multicenter, first-in-human phase 1 study evaluated intratumoral MEDI1191 plus intravenous durvalumab in adult patients with advanced solid tumors who had progressed on ≥ 1 line of prior therapy (immunotherapy permitted). Cutaneous or subcutaneous lesions or deep-seated lesions were injected; patients had ≥ 1 noninjected lesions measurable per RECIST v1.1. Target lesions were noninjected. MEDI1191 and durvalumab were given sequentially or concurrently. Primary objectives were safety and determination of maximum tolerated dose (MTD); seconday objectives included efficacy. Sixty-one patients were treated. Median number of prior therapies was 4 (range 1-17); 39 patients (63.9%) received prior anti-PD-(L)1 therapy. Treatment-emergent adverse events (TEAEs) occurred in 96.7% of patients; grade 3 or 4 TEAEs in 41.0%. There were no dose-limiting toxicities, and the MTD was not reached. Objective response rate was 9.8%, including one confirmed complete response and five confirmed partial responses. Duration of response was 2.7 to 22.3 months; median was not reached. Responses occurred in injected lesions, local noninjected lesions, and distant lesions. Three of 39 patients with prior anti-PD-(L)1 therapy had partial responses. The authors conclude that the combination of MEDI1191 and durvalumab was tolerated, with encouraging preliminary antitumor activity in these heavily pretreated patients.