{ "abstract": "Purpose:: MEDI1191 is a lipid nanoparticle–formulated messenger RNA (mRNA) designed to induce local interleukin (IL) 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).\n\nPatients and 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 lesion measurable per Response Evaluation Criteria in Solid Tumors (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.\n\nResults:: As of February 27, 2023, 61 patients were treated. Patients had a median of four prior regimens (range, 1–17); 39 (63.9%) received prior anti–programmed cell death protein 1/programmed cell death ligand 1 [PD-(L)1] immunotherapy. Treatment-emergent adverse events (TEAE) 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. The objective response rate was 9.8%, including 1 confirmed complete response and 5 confirmed partial responses (PR). The duration of response was 2.7 to 22.3 months; the 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.\n\nConclusions:: MEDI1191 and durvalumab were tolerated. Preliminary antitumor activity was encouraging in these heavily pretreated patients, including patients previously treated with immune checkpoint inhibitors.", "abstract_shown": true, "affiliations": [ "Division of Hematology/Oncology, Legorreta Cancer Center, Brown University, Providence, Rhode Island.", "Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.", "Department of Hematology/Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.", "Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain.", "Department of Medical Oncology, Moores Cancer Center, University of California San Diego, La Jolla, California.", "Early-Phase Drug Development, University of Texas MD Anderson Cancer Center, Houston, Texas.", "Medical Oncology, Cutaneous Oncology, The Angeles Clinic and Research Institute, A Cedars Sinai Affiliate, Los Angeles, California.", "University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California.", "Vall d’Hebron Barcelona Hospital Campus, IIS IR-HUVH, Barcelona, Spain.", "Department of Medicine, UAB, Barcelona, Spain.", "Translational Medicine, Oncology R&D, AstraZeneca, Waltham, Massachusetts.", "Oncology Data Science & AI, Early Data Science, AstraZeneca, Gaithersburg, Maryland.", "CPQP, Clinical Pharmacology and Safety Sciences, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.", "Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, AstraZeneca, Gaithersburg, Maryland.", "Early Oncology Statistics, Oncology R&D, AstraZeneca, Gaithersburg, Maryland.", "Translational Medicine, Oncology, AstraZeneca, Gaithersburg, Maryland.", "Early Oncology Clinical Development, Oncology R&D, AstraZeneca, Gaithersburg, Maryland.", "Late Development Oncology, Oncology R&D, AstraZeneca, Waltham, Massachusetts.", "Early Global Development, Oncology R&D, AstraZeneca, Barcelona, Spain.", "Research Department, The Angeles Clinic and Research Institute, A Cedars Sinai Affiliate, Los Angeles, California." ], "article_type": "research article", "arxiv": null, "author_total": 20, "authors": [ { "affs": [ 0 ], "name": "Benedito A. Carneiro", "orcid": "0000-0002-5468-1126" }, { "affs": [ 1 ], "name": "Thomas Marron", "orcid": "0000-0001-5903-8191" }, { "affs": [ 2 ], "name": "Dmitriy Zamarin", "orcid": "0000-0002-0094-0161" }, { "affs": [ 3 ], "name": "Eduardo Castañón", "orcid": "0000-0003-2957-4414" }, { "affs": [ 4 ], "name": "Sandip Pravin Patel", "orcid": "0000-0002-8387-4840" }, { "affs": [ 5 ], "name": "Vivek Subbiah", "orcid": "0000-0002-6064-6837" }, { "affs": [ 6 ], "name": "Inderjit Mehmi", "orcid": "0000-0002-2253-2206" }, { "affs": [ 7 ], "name": "Anthony El-Khoueiry", "orcid": "0000-0002-9053-3841" }, { "affs": [ 8, 9 ], "name": "Arjun Oberoi", "orcid": "0009-0003-2207-6524" }, { "affs": [ 10 ], "name": "Michael Abadier", "orcid": "0009-0002-9201-2502" }, { "affs": [ 11 ], "name": "Emily C. Jennings", "orcid": "0000-0002-7687-5319" }, { "affs": [ 12 ], "name": "Vincent Dubois", "orcid": "0000-0002-7423-5473" }, { "affs": [ 13 ], "name": "Zhongying Chen", "orcid": "0009-0004-3326-5782" }, { "affs": [ 13 ], "name": "Xiaoru Chen", "orcid": "0009-0009-7351-0259" }, { "affs": [ 14 ], "name": "Nairouz Elgeioushi", "orcid": "0009-0009-5303-9535" }, { "affs": [ 15 ], "name": "Nicholas M. Durham", "orcid": "0000-0003-1065-8474" }, { "affs": [ 16 ], "name": "Benjamin Ridgway", "orcid": "0009-0001-4408-6454" }, { "affs": [ 17 ], "name": "Paula G. Fraenkel", "orcid": "0000-0001-8894-0117" }, { "affs": [ 18 ], "name": "Analia Azaro", "orcid": "0000-0001-6852-4925" }, { "affs": [ 19 ], "name": "Omid Hamid", "orcid": "0000-0002-8238-4655" } ], "bibtex": "https://research.draconitic.com/paper/14hpa2r2f3690.bib", "cited_by": 2, "doi": "10.1158/1078-0432.ccr-25-4865", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13725328/", "id": "14hpa2r2f3690", "issns": [ "1078-0432", "1557-3265" ], "landing_url": "https://doi.org/10.1158/1078-0432.ccr-25-4865", "language": "en", "licence": "CC-BY-NC-ND-4.0", "licence_label": "CC BY-NC-ND 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Checkpoint Blockade" ], [ "heading", "Clinical Trial Results" ], [ "heading", "Clinical Trials: Immunotherapy" ], [ "heading", "Combination Immunotherapy" ], [ "heading", "Immunotherapy" ], [ "heading", "Phase I clinical trials" ], [ "openalex", "2730|Cancer Immunotherapy and Biomarkers" ] ], "openalex": "W7203685086", "pdf_url": null, "pmcid": "PMC13725328", "pmid": "42611979", "published": "2026-08-18", "publisher": null, "ris": "https://research.draconitic.com/paper/14hpa2r2f3690.ris", "sources": [ { "first_seen": "2026-11-04T12:23:45Z", "native_id": "PMC13725328", "source": "pmc", "url": "https://doi.org/10.1158/1078-0432.ccr-25-4865" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers", "subfield": "oncology" } ], "title": "Safety and Efficacy of Intratumoral MEDI1191, an IL12 mRNA Lipid Nanoparticle, plus Intravenous Durvalumab in Patients with Advanced Solid Tumors: A First-in-Human Study", "title_text": "Safety and Efficacy of Intratumoral MEDI1191, an IL12 mRNA Lipid Nanoparticle, plus Intravenous Durvalumab in Patients with Advanced Solid Tumors: A First-in-Human Study", "type": "peer-reviewed", "updated_at": "2026-11-06T12:21:37Z", "url": "https://research.draconitic.com/paper/14hpa2r2f3690", "venue": "Clinical Cancer Research", "versions": [] }