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760 Interim PK/PD, safety and efficacy data of monotherapy dose escalation of a phase 1/2 study with MDNA11 in patients with advanced solid tumors
  1. Minh D To1,
  2. Rosemina Merchant1,
  3. Victoria Atkinson2,
  4. Philippe Bedard3,
  5. Warren Brenner4,
  6. Melissa Coello1,
  7. Jesus Fuentes Antras3,
  8. Carole Galligan1,
  9. Charlotte Lemech5,
  10. Peter Lloyd6,
  11. Sudhir Madduri Karanam1,
  12. Kim Margolin7,
  13. Matthen Mathew4,
  14. Amy Prawira8,
  15. Sajeve Thomas9,
  16. Przemyslaw Twardowski7,
  17. Arash Yavari10 and
  18. Fahar Merchant1
  1. 1Medicenna Therapeutics, Toronto, ON, Canada
  2. 2Princess Alexandra Hospital, Woolloongabba, QLD, Australia
  3. 3Princess Margaret Hospital, Toronto, ON, Canada
  4. 4Boca Raton Regional Hospital, Boca Raton, FL, USA
  5. 5Scientia Clinical Research, Sydney, NSW, Australia
  6. 6KinDyn Consulting Ltd., London, UK
  7. 7Saint John’s Cancer Institute, Providence Saint John’s Health Center, Santa Monica, CA, USA
  8. 8Obatica Pty Ltd., Sydney, NSW, Australia
  9. 9Orlando Health Cancer Institute, Orlando, FL, USA
  10. 10University of Oxford, London, UK
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background MDNA11 is an albumin-fused long-acting IL-2 agonist with enhanced affinity for IL-2Rb and no binding to IL-2Ra, resulting in potent CD8+ T and NK cell activation, limited Treg increase and reduced toxicities.1 ABILITY (A Beta-only IL-2 ImmunoTherapY) is a Phase 1/2 study evaluating the safety, pharmacokinetic (PK), pharmacodynamic (PD) and preliminary clinical activity of MDNA11 as monotherapy and in combination with Prembrolizumab in pre-treated patients with advanced solid tumors.

Methods The dose-escalation phase of ABILITY uses a modified 3+3 design to determine the recommended dose for expansion (RDE). Patients received a fixed dose of 3, 10 or 30 μg/kg (dose levels 1–3; DL1–3) by intravenous infusion on a Q2W schedule. Step-up dosing was implemented starting at DL4 where patients received 2 or 3 priming doses prior to the target dose of 60 μg/kg (DL4), 90 μg/kg (DL5) or 120 μg/kg (DL6). Primary endpoints include incidence and severity of adverse events (AEs). Secondary endpoints include assessment of PK, PD and tumor response per RECISTv1.1 and iRECIST

Results As of June 22, 2023, twenty dose limiting toxicity (DLT)-evaluable patients have been dosed with MDNA11 during monotherapy dose escalation (3–120 μg/kg). Tumor types enrolled included melanoma (n=11), renal cell carcinoma (n=2), pancreatic ductal adenocarcinoma (PDAC; n=2), sarcoma (n=2), tonsillar squamous cell carcinoma (n=1), gastro-esophageal adenocarcinoma (n=1) and lung adenocarcinoma (n=1). PK analysis showed dose-dependent increase in MDNA11 exposure. Immune profiling showed robust lymphocyte expansion, including increase in CD8+ T and NK cells and limited change in Tregs. There were no DLTs observed. The most common AEs were infusion related reaction (65%) comprising pyrexia (50%), nausea (45%), chills (35%), fatigue (30%) and diarrhea (25%), with the majority being grade 1–2 and resolved within 48–72 hours. Transient (~ 1week duration) transaminases increase was seen in 25% of patients. Tumor response was evaluated in 19 patients. Single-agent activity included stable disease (SD) observed in 6 patients, including a melanoma patient with SD beyond 1.5 year, and an ongoing partial response (PR) in a PDAC patient who had previously progressed on immune checkpoint inhibitor and is currently continuing on MDNA11 for > 1 year.

Conclusions MDNA11 is well tolerated with no DLTs up to target dose of 120 μg/kg on a Q2W schedule. Evidence of clinical activity includes SD in 6 of 19 patients in addition to a durable PR in a PDAC patient. Data analysis is ongoing to inform RDE selection.

Acknowledgements We are grateful to all patients participating in this study.

Trial Registration NCT: 05086692


  1. Merchant R, Galligan C, Munegowda MA, et al. Fine-tuned long-acting interleukin-2 superkine potentiates durable immune responses in mice and non-human primate. 2022;10:e003155.

Ethics Approval The study was conducted with approval from institutional ethics committee and informed consent from participants.

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