Safety and efficacy of intratumoral MEDI1191, an IL-12 mRNA lipid nanoparticle, plus intravenous durvalumab in patients with advanced solid tumors: a first-in-human study.

PURPOSE: MEDI1191 is a lipid nanoparticle-formulated mRNA designed to induce local interleukin-12 production and intensify antitumor T cell responses. We report dose-escalation results from a first-in-human, open-label, phase I study of intratumoral MEDI1191 plus intravenous durvalumab (NCT03946800). METHODS: Patients were ≥18 years with advanced/metastatic solid tumors and had progressed on ≥1 line of prior therapy (immunotherapy permitted). Cutaneous/subcutaneous (Parts 1A and 1B) or deep-seated lesions (Part 1D) were injected; patients had ≥1 noninjected lesions measurable per RECIST v1.1. Target lesions were noninjected. MEDI1191 and durvalumab were given sequentially (Part 1A) or concurrently (Parts 1B and 1D). Primary objectives were safety and determination of maximum tolerated dose (MTD). Secondary objectives included efficacy. RESULTS: As of February 27, 2023, 61 patients were treated. Patients had a median of 4 prior regimens (range, 1-17); 39 (63.9%) received prior anti-PD-(L)1 immunotherapy. Treatment-emergent adverse events (TEAEs) occurred in 96.7% of patients and 41.0% experienced Grade 3/4 TEAEs. There were no dose-limiting toxicities. The MTD was not reached. Objective response rate was 9.8%, including 1 confirmed complete response and 5 confirmed partial responses (PRs). Duration of response was 2.7-22.3 months; median was not reached. Responses occurred in injected lesions, local noninjected lesions, and distant lesions. Three of the 39 patients with prior anti-PD-(L)1 therapy had PRs. CONCLUSIONS: MEDI1191 and durvalumab were tolerated. Preliminary antitumor activity was encouraging in these heavily pretreated patients, including patients previously treated with immune checkpoint inhibitors.