Sponsor: Medicenna Therapeutics, Inc. (industry)
Phase: 1/2
Start date: Aug. 27, 2021
Planned enrollment: 115
MDNA11 (also called MDNA109FEAA) is an intravenously administered, long‑acting interleukin‑2 (IL‑2) “superkine” engineered to preferentially stimulate IL‑2Rβ/γ (CD122/CD132) on CD8 T and NK cells while minimizing IL‑2Rα (CD25) engagement and Treg activation. It is fused to human albumin to extend half‑life. MDNA11 is being evaluated in the Phase 1/2 ABILITY‑1 trial (NCT05086692) as monotherapy and in combination with pembrolizumab in advanced solid tumors. (pmc.ncbi.nlm.nih.gov)
Human data are from the ongoing Phase 1/2 ABILITY‑1 trial in heavily pretreated solid tumors.
Note: As of October 7, 2025, no randomized or registrational efficacy data have been published.
Disclosure: Several efficacy and safety figures above derive from sponsor press releases/meeting news and should be considered preliminary until validated in peer‑reviewed publications or full conference reports.
Last updated: Oct 2025
Goal: Evaluate the safety, tolerability, recommended doses for expansion, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of MDNA11, a long-acting IL-2 beta-only superkine, administered as monotherapy or in combination with pembrolizumab in advanced solid tumors.
Patients: Adults (≥18 years) with histologically or cytologically confirmed locally advanced or metastatic solid tumors, ECOG 0–1, measurable disease by RECIST v1.1, adequate organ function, and life expectancy ≥12 weeks. Key exclusions include active CNS metastases (unless treated and stable), recent systemic therapy or radiotherapy, significant autoimmune disease or need for immunosuppression, severe cardiopulmonary disease, active infections including HBV/HCV, prior allogeneic transplant, and pregnancy or lactation.
Design: Phase 1/2, multi-center, open-label, non-randomized dose-escalation and expansion study with four parts: MDNA11 monotherapy dose escalation, monotherapy expansion in select tumor types, MDNA11 plus pembrolizumab dose escalation, and combination expansion. Tumor assessments by CT/MRI every 8 weeks using RECIST v1.1 and iRECIST, with treatment beyond progression allowed per protocol criteria.
Treatments: MDNA11 as monotherapy and in combination with pembrolizumab. MDNA11 is an engineered interleukin-2 superkine (MDNA109FEAA) fused to human albumin to extend half-life and designed to preferentially bind IL-2Rβ while avoiding IL-2Rα, thereby activating effector CD8+ T cells and NK cells with minimal Treg stimulation. Early clinical data from the ongoing program have shown signals of activity, including responses in checkpoint inhibitor–refractory populations, and a favorable safety profile without dose-limiting toxicities up to 120 μg/kg; most adverse events have been grade 1–2 and transient. The combination with pembrolizumab has produced early responses in select tumor types, supporting biological synergy with checkpoint blockade. Pembrolizumab is a PD-1 inhibitor used as standard immunotherapy across multiple solid tumors.
Outcomes: Primary: determination of recommended doses for expansion for monotherapy and combination based on dose-limiting toxicities; incidence of treatment-related and treatment-emergent adverse events. Secondary: pharmacokinetics of MDNA11 (Cmax, Tmax, AUClast), immunogenicity (anti-drug antibodies), pharmacodynamics (circulating immune cell subsets and cytokines), and anti-tumor activity by RECIST v1.1 and iRECIST including ORR, DCR, and PFS. Other: changes in tumor microenvironment immune characteristics, including tumor-infiltrating lymphocytes.
Burden on patient: High. As an early-phase dose-escalation/expansion study with both monotherapy and combination cohorts, patients should anticipate frequent clinic visits, intensive safety monitoring, and serial PK and PD blood draws, particularly around dosing days. Imaging is scheduled every 8 weeks, and optional or mandated tumor biopsies for translational analyses may be requested, adding procedural burden. Travel demands may be substantial due to the visit frequency typical of phase 1/2 immunotherapy trials and potential infusion-related monitoring periods.
Last updated: Oct 2025
Key Inclusion Criteria:
1. Aged at least 18 years (inclusive at the time of informed consent).
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
3. Must be able and willing to provide written informed consent prior to start of any study procedures and assessments and must be willing to comply with all study procedures.
4. Histologically or cytologically confirmed locally advanced or metastatic solid tumor (see tumor types listed under conditions)
5. Demonstrated adequate organ function
6. Measurable disease as per Response Evaluation Criteria in Solid Tumors, (RECIST v1.1) and documented by CT and/or MRI.
7. Life expectancy of ≥ 12 weeks.
8. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and within 72 hours before the first dose of study drug(s). Women must not be breastfeeding.
9. Agree to use highly effective contraception methods. WOCBP must agree to use highly effective birth control.
Key Exclusion Criteria:
1. Last administration of prior antitumor therapy:
* Prior systemic anti-cancer therapy including investigational agents within 4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs) prior to start of treatment.
* Prior radiotherapy within 2 weeks prior to start of treatment or has had a history of radiation pneumonitis. A 1-week washout is required for palliative radiation (\<2 weeks of radiotherapy) to non-CNS disease.
* Radiation therapy to the lung that is \> 30Gy within 6 months prior to start of treatment.
* Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to start of treatment. Concomitant participation in an observational study must be discussed on a case-by-case basis with the MM for approval.
2. Has known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to start of treatment, subject to discussion with MM.
3. Active malignancy (other than the disease under treatment in the study) within the previous 3 years except for curable cancers.
4. Condition requiring long-term systemic treatment with either corticosteroids \> 10 mg daily prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to start of treatment.
5. Clinically significant active, known or suspected autoimmune disease, or diseases that can be exacerbated with immunotherapy.
6. Severe pulmonary, cardiac or other systemic disease.
7. Known hepatitis B or C virus infection.
8. Females who are pregnant or lactating or planning to become pregnant during the study.
9. Has had an allogeneic tissue/solid organ transplant.
10. Active infection requiring systemic therapy.
11. Any medical, emotional or psychiatric condition that interfere with the patient's ability to adhere to the protocol
12. Any other underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug(s) unsafe or obscure the interpretation of toxicity determination or adverse events.
13. Known severe hypersensitivity to any component of study drug(s).
14. Inability to comply with study and follow up procedures as judged by the Investigator.
Randwick, New South Wales, 2031, Australia
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Status: Recruiting
Sydney, New South Wales, 2109, Australia
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Greenslopes, Queensland, 4120, Australia
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Buderim, Queensland, 4556, Australia
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Status: Recruiting
Toronto, Ontario, M4W 3E2, Canada
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Status: Recruiting
Dublin, D07 R2WY, Ireland
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Status: Recruiting
Lisbon, 1649-035, Portugal
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Status: Recruiting
Porto, 4200-072, Portugal
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Status: Recruiting
Seoul, Gangnam-gu, South Korea
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Status: Active, not recruiting
Seongnam-si, Gyeonggi-do, South Korea
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Status: Active, not recruiting
Suwon, Gyeonggi-do, South Korea
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Status: Active, not recruiting
Seoul, Jongno-gu, South Korea
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Status: Active, not recruiting
Torrejón, 28850, Spain
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Status: Recruiting
Badalona, 08916, Spain
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Status: Recruiting
Barcelona, 08023, Spain
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Status: Recruiting
Barcelona, 08041, Spain
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Status: Recruiting
Madrid, 28034, Spain
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Madrid, 28040, Spain
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Status: Recruiting
Madrid, 28050, Spain
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Status: Recruiting
Oviedo, 33011, Spain
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Status: Recruiting
Santa Monica, California, 90404, United States
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Status: Recruiting
San Diego, California, 92123, United States
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Status: Recruiting
San Francisco, California, 94158, United States
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Status: Active, not recruiting
Boca Raton, Florida, 33486, United States
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Status: Recruiting
Atlanta, Georgia, 30322, United States
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Status: Recruiting
Detroit, Michigan, 48201, United States
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Status: Recruiting
Houston, Texas, 77030, United States
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Status: Active, not recruiting