A phase 1 study of the CD40 agonist MEDI5083 in combination with durvalumab in patients with advanced solid tumors

  • Immunotherapy. 2024;16(11):759-774. doi: 10.1080/1750743X.2024.2359359.
Ben Tran  1 ,  Mark Voskoboynik  2  3 ,  Johanna Bendell  4 ,  Martin Gutierrez  5 ,  Charlotte Lemech  6  7 ,  Daphne Day  3  8 ,  Sophia Frentzas  3  8 ,  Ignacio Garrido-Laguna  9 ,  Nathan Standifer  10 ,  Fujun Wang  11 ,  Charles Ferte  12 ,  Yue Wang  12 ,  Mayukh Das  12 ,  Benedito A Carneiro  13
Affiliations
  • 1. Peter MacCallum Cancer Centre, Melbourne, 8006, Australia.
  • 2. Nucleus Network, Melbourne, 3004, Australia.
  • 3. Monash University, Melbourne, 3004, Australia.
  • 4. Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN 37203, USA.
  • 5. Hackensack University Medical Center, Hackensack, NJ 07601, USA.
  • 6. Scientia Clinical Research, Randwick, 2031, Australia.
  • 7. The University of New South Wales, Sydney, 2052, Australia.
  • 8. Monash Medical Centre, Clayton, 3800, Australia.
  • 9. Huntsman Cancer Institute, Salt Lake City, UT 84132, USA.
  • 10. Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, South San Francisco, CA 94080, USA.
  • 11. Oncology Biometrics, AstraZeneca, Gaithersburg, MD 20878,USA.
  • 12. AstraZeneca, Gaithersburg, MD 20878,USA.
  • 13. Legorreta Cancer Center at Brown University, Lifespan Cancer Institute, Providence, RI 02903,USA.
PMID: 39264730 DOI: 10.1080/1750743X.2024.2359359
Abstract

Aim: This first-in-human study evaluated safety and efficacy of CD40 agonist MEDI5083 with durvalumab in patients with advanced solid tumors.Methods: Patients received MEDI5083 (3-7.5 mg subcutaneously every 2 weeks × 4 doses) and durvalumab (1500 mg every 4 weeks) either sequentially (N = 29) or concurrently (N = 9). Primary end point was safety; secondary end points included efficacy.Results: Thirty-eight patients received treatment. Most common adverse events (AEs) were injection-site reaction (ISR; sequential: 86%; concurrent: 100%), fatigue (41%; 33%), nausea (20.7%; 55.6%) and decreased appetite (24.1%; 33.3%). Nine patients had MEDI5083-related grade ≥3 AEs with ISR being the most common. Two patients experienced dose limiting toxicities (ISR). One death occurred due to a MEDI5083-related AE. MEDI5083 maximum tolerated dose was 5 mg. Objective response rate was 2.8% (1 partial response and 11 stable disease).Conclusion: MEDI5083 toxicity profile limits its further development.

Keywords
CD40; CD40L; cancer; efficacy; fusion protein; safety.
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