Sponsor: Medicenna Therapeutics, Inc. (industry)
Phase: 1/2
Start date: Aug. 27, 2021
Planned enrollment: 115
MDNA11 is an investigational, long-acting interleukin-2 (IL-2) agonist being developed by Medicenna for advanced solid tumors. It is under evaluation intravenously as monotherapy and with pembrolizumab in the open-label Phase 1/2 ABILITY-1 trial (NCT05086692). No randomized results or peer-reviewed full clinical publication are available; current evidence comes primarily from interim conference reports. (clinicaltrials.gov)
MDNA11 consists of the engineered IL-2 variant MDNA109FEAA fused to albumin to extend systemic exposure. The IL-2 component contains mutations that enhance binding to IL-2 receptor β (CD122) while eliminating binding to IL-2 receptor α (CD25). This “β-enhanced, not-α” profile is intended to preferentially expand cytotoxic CD8-positive T cells and natural-killer cells while limiting stimulation of regulatory T cells. Preclinical studies reported approximately 30-fold greater affinity for CD122 than recombinant IL-2, enhanced STAT5 signaling, and reduced regulatory-T-cell activation. (jitc.bmj.com)
In the most detailed independently published conference abstract, with a November 18, 2024 cutoff, 5 of 20 efficacy-evaluable, checkpoint-inhibitor–experienced patients receiving monotherapy at ≥60 µg/kg responded (ORR 25%; 95% CI 6%–44%): one complete response in melanoma and four partial responses—two in melanoma and two in MSI-high pancreatic cancer. Six additional patients had stable disease, three lasting over six months. (aacrjournals.org)
A later ESMO Immuno-Oncology 2025 update reported higher response rates in small, selected expansion cohorts—for example, 42% ORR (5/12) when MDNA11 was given immediately after checkpoint-inhibitor progression. Tumor-specific results included 38% ORR in melanoma, 22% in MSI-high cancers, and, with pembrolizumab, 50% in MSS endometrial cancer. These figures were reported by the sponsor and remain preliminary, nonrandomized, and based on small subgroups. (ir.medicenna.com)
In the 2025 AACR abstract, no protocol-defined dose-limiting toxicities were observed through 120 µg/kg every two weeks. Most treatment-related adverse events were grade 1–2, transient, and resolved within 72 hours. Earlier conference data identified infusion-related reactions, fever, nausea, chills, and fatigue as common events. Approximately 94% of treatment-related events in a 2024 report were grade 1–2; no maximum tolerated dose had been reached. (aacrjournals.org)
Last updated: Sep 2026
Goal: Determine tolerable doses of MDNA11 alone and with pembrolizumab for expansion, characterize safety and pharmacology, and assess preliminary antitumor activity in advanced solid tumors.
Patients: Adults with locally advanced or metastatic solid tumors, measurable disease, ECOG performance status 0–1, adequate organ function, and life expectancy of at least 12 weeks. Key exclusions include active CNS metastases, clinically significant autoimmune disease, systemic immunosuppression, active infection, and serious organ disease.
Design: Multicenter, open-label phase 1/2 study with separate monotherapy and combination dose-escalation and tumor-specific expansion parts. There is no randomized comparator. Treatment may continue beyond initial progression if protocol criteria are met.
Treatments: MDNA11 is an investigational, long-acting, albumin-fused IL-2 agonist engineered to favor IL-2 receptor β signaling in CD8-positive T cells and natural killer cells while limiting regulatory T-cell stimulation. In preliminary, nonrandomized conference data, 5 of 20 evaluable checkpoint-inhibitor–experienced patients receiving MDNA11 monotherapy at doses of at least 60 µg/kg had a response; these small-cohort findings do not establish efficacy. Pembrolizumab is a standard PD-1–blocking immune checkpoint inhibitor studied here in combination with MDNA11.
Outcomes: Primary measures are dose-limiting toxicities, recommended monotherapy and combination expansion doses, and treatment-related and treatment-emergent adverse events. Secondary measures include MDNA11 pharmacokinetics, anti-drug antibodies, circulating immune-cell and cytokine changes, overall response rate, disease control rate, and progression-free survival. Changes in tumor-infiltrating lymphocytes are also assessed.
Burden on patient: Likely high, particularly during dose escalation: patients receive study treatment and undergo safety monitoring, pharmacokinetic and immune-marker blood sampling, and CT or MRI approximately every eight weeks. Repeated clinic visits and travel may be more demanding than routine care. The provided information does not establish whether research tumor biopsies are required.
Last updated: Sep 2026
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.
Sydney, New South Wales, 2109, Australia
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Status: Recruiting
Randwick, New South Wales, 2031, 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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Porto, 4200-072, Portugal
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Status: Recruiting
Lisbon, 1649-035, Portugal
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Status: Recruiting
Oviedo, 33011, Spain
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Status: Recruiting
Madrid, 28050, Spain
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Madrid, 28034, Spain
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Torrejón, 28850, Spain
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Status: Recruiting
Barcelona, 08041, 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
Madrid, 28040, 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
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
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
San Francisco, California, 94158, United States
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Status: Active, not recruiting
Houston, Texas, 77030, United States
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Status: Active, not recruiting