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Peer-reviewedCC BY-NC-ND 4.0Clinical Cancer Research

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

  • Benedito A. Carneiro1
  • Thomas Marron2
  • Dmitriy Zamarin3
  • Eduardo Castañón4
  • Sandip Pravin Patel5
  • Vivek Subbiah6
  • Inderjit Mehmi7
  • Anthony El-Khoueiry8
  • Arjun Oberoi9,10
  • Michael Abadier11
  • Emily C. Jennings12
  • Vincent Dubois13
8 more authors
  • Zhongying Chen14
  • Xiaoru Chen14
  • Nairouz Elgeioushi15
  • Nicholas M. Durham16
  • Benjamin Ridgway17
  • Paula G. Fraenkel18
  • Analia Azaro19
  • Omid Hamid20
20 affiliations
  1. 1Division of Hematology/Oncology, Legorreta Cancer Center, Brown University, Providence, Rhode Island.
  2. 2Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.
  3. 3Department of Hematology/Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
  4. 4Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain.
  5. 5Department of Medical Oncology, Moores Cancer Center, University of California San Diego, La Jolla, California.
  6. 6Early-Phase Drug Development, University of Texas MD Anderson Cancer Center, Houston, Texas.
  7. 7Medical Oncology, Cutaneous Oncology, The Angeles Clinic and Research Institute, A Cedars Sinai Affiliate, Los Angeles, California.
  8. 8University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California.
  9. 9Vall d’Hebron Barcelona Hospital Campus, IIS IR-HUVH, Barcelona, Spain.
  10. 10Department of Medicine, UAB, Barcelona, Spain.
  11. 11Translational Medicine, Oncology R&D, AstraZeneca, Waltham, Massachusetts.
  12. 12Oncology Data Science & AI, Early Data Science, AstraZeneca, Gaithersburg, Maryland.
  13. 13CPQP, Clinical Pharmacology and Safety Sciences, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
  14. 14Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, AstraZeneca, Gaithersburg, Maryland.
  15. 15Early Oncology Statistics, Oncology R&D, AstraZeneca, Gaithersburg, Maryland.
  16. 16Translational Medicine, Oncology, AstraZeneca, Gaithersburg, Maryland.
  17. 17Early Oncology Clinical Development, Oncology R&D, AstraZeneca, Gaithersburg, Maryland.
  18. 18Late Development Oncology, Oncology R&D, AstraZeneca, Waltham, Massachusetts.
  19. 19Early Global Development, Oncology R&D, AstraZeneca, Barcelona, Spain.
  20. 20Research Department, The Angeles Clinic and Research Institute, A Cedars Sinai Affiliate, Los Angeles, California.
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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).

Patients 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.

Results:: 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.

Conclusions:: MEDI1191 and durvalumab were tolerated. Preliminary antitumor activity was encouraging in these heavily pretreated patients, including patients previously treated with immune checkpoint inhibitors.

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Cite

BibTeXRIS
BibTeX
@article{carneiro2026safety,
  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}},
  author = {Benedito A. Carneiro and Thomas Marron and Dmitriy Zamarin and Eduardo Castañón and Sandip Pravin Patel and Vivek Subbiah and Inderjit Mehmi and Anthony El-Khoueiry and Arjun Oberoi and Michael Abadier and Emily C. Jennings and Vincent Dubois and Zhongying Chen and Xiaoru Chen and Nairouz Elgeioushi and Nicholas M. Durham and Benjamin Ridgway and Paula G. Fraenkel and Analia Azaro and Omid Hamid},
  journal = {Clinical Cancer Research},
  year = {2026},
  month = aug,
  doi = {10.1158/1078-0432.ccr-25-4865},
  url = {https://doi.org/10.1158/1078-0432.ccr-25-4865},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - 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
AU  - Benedito A. Carneiro
AU  - Thomas Marron
AU  - Dmitriy Zamarin
AU  - Eduardo Castañón
AU  - Sandip Pravin Patel
AU  - Vivek Subbiah
AU  - Inderjit Mehmi
AU  - Anthony El-Khoueiry
AU  - Arjun Oberoi
AU  - Michael Abadier
AU  - Emily C. Jennings
AU  - Vincent Dubois
AU  - Zhongying Chen
AU  - Xiaoru Chen
AU  - Nairouz Elgeioushi
AU  - Nicholas M. Durham
AU  - Benjamin Ridgway
AU  - Paula G. Fraenkel
AU  - Analia Azaro
AU  - Omid Hamid
PY  - 2026
DA  - 2026/08/18
JO  - Clinical Cancer Research
DO  - 10.1158/1078-0432.ccr-25-4865
UR  - https://doi.org/10.1158/1078-0432.ccr-25-4865
AB  - 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).  Patients 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.  Results:: 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.  Conclusions:: MEDI1191 and durvalumab were tolerated. Preliminary antitumor activity was encouraging in these heavily pretreated patients, including patients previously treated with immune checkpoint inhibitors.
SN  - 1078-0432
SN  - 1557-3265
ER  -