Sponsor: Medicenna Therapeutics, Inc. (industry)
Phase: 1/2
Start date: Aug. 27, 2021
Planned enrollment: 115
MDNA11, also known as MDNA109FEAA, is an investigational long-acting interleukin-2 (IL-2) super-agonist developed by Medicenna Therapeutics. It is designed to selectively stimulate immune effector cells, such as CD8⁺ T cells and natural killer (NK) cells, while minimizing activation of regulatory T cells (Tregs). MDNA11 is currently being evaluated in the Phase 1/2 ABILITY-1 study (NCT05086692) as both a monotherapy and in combination with pembrolizumab (KEYTRUDA®) in patients with advanced or metastatic solid tumors.
MDNA11 is engineered to enhance binding to the IL-2 receptor beta (CD122) subunit without engaging the IL-2 receptor alpha (CD25) subunit. This selective binding promotes the activation and proliferation of anti-cancer immune cells, including CD8⁺ T cells and NK cells, while reducing stimulation of Tregs, which can suppress immune responses. The fusion of MDNA11 to a recombinant human albumin scaffold extends its half-life and facilitates accumulation in tumor tissues and tumor-draining lymph nodes.
In the ongoing ABILITY-1 study, MDNA11 has demonstrated promising anti-tumor activity:
Monotherapy Dose Expansion Cohort: Among 10 patients with advanced solid tumors who had previously failed immune checkpoint inhibitor (ICI) therapy, MDNA11 achieved an objective response rate (ORR) of 30%, including three partial responses (PRs). Notably, two of these PRs were observed in patients with microsatellite instability-high (MSI-H) pancreatic ductal adenocarcinoma (PDAC), resulting in an ORR of 66.7% in this subgroup. Additionally, a complete response (CR) was reported in a patient with cutaneous melanoma. (stocktitan.net)
Combination with Pembrolizumab: In the combination dose escalation cohorts, MDNA11, administered with pembrolizumab, showed encouraging preliminary signs of anti-tumor activity. Among five heavily pre-treated efficacy-evaluable patients, tumor control (PR or stable disease) was observed in four patients, including a PR in a microsatellite-stable (MSS) colon cancer patient. (stocktitan.net)
MDNA11 has exhibited a favorable safety profile in clinical evaluations:
Monotherapy: No dose-limiting toxicities (DLTs) or evidence of vascular leak syndrome were reported during the dose escalation phase. The majority (94%) of treatment-related adverse events (TRAEs) were Grade 1 or 2 and resolved within 48 hours. (stocktitan.net)
Combination Therapy: In combination with pembrolizumab, MDNA11 was well tolerated, with no DLTs or new safety signals observed. This favorable safety profile allowed for dose escalation to 120 µg/kg in the combination therapy cohorts. (stocktitan.net)
Last updated: Apr 2025
Goal: The trial aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of MDNA11 both as a monotherapy and in conjunction with pembrolizumab in patients with advanced solid tumors.
Patients: The study focuses on adult patients aged 18 and over with locally advanced or metastatic solid tumors. Participants must have an ECOG performance status of 0 or 1, a minimum life expectancy of 12 weeks, and demonstrable adequate organ function.
Design: This is a non-randomized, open-label, dose-escalation and expansion Phase 1/2 study conducted across multiple clinical sites. The study phases include dose escalation and expansion for both monotherapy and combination therapy arms.
Treatments: The investigational drug MDNA11, a long-acting recombinant interleukin-2 (rIL-2) Superkine, is the focal therapy, engineered to target the IL-2 beta receptor on immune effector cells. This design aims to enhance anti-tumor immunity while reducing undesired Treg activation. Combined with pembrolizumab, preliminary data has shown promising responses, including complete responses in some tumor types.
Outcomes: The trial measures the recommended dose for expansion for both monotherapy and combination, along with incidence rates of dose-limiting toxicities, treatment-related adverse events, and treatment-emergent adverse events. Secondary outcomes focus on pharmacokinetic properties such as Cmax, Tmax, and AUClast, immunogenicity, pharmacodynamic effects, anti-tumor activity (ORR, DCR, PFS), and changes in tumor microenvironment immunology.
Burden on patient: Patients will likely face a moderate burden due to frequent medical visits for pharmacokinetic blood sampling, routine imaging every eight weeks, and regular clinical assessments. Additional travel and time commitment will occur for participating at up to 30 clinical sites. However, the trial procedures resemble standard early-phase trial demands for investigational medications, potentially difficult for patients with limited mobility or those living far from trial locations.
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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Status: Recruiting
Greenslopes, Queensland, 4120, Australia
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Status: Recruiting
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
Seoul, Gangnam-gu, Korea, Republic of
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Status: Active, not recruiting
Seongnam-si, Gyeonggi-do, Korea, Republic of
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Status: Active, not recruiting
Suwon-si, Gyeonggi-do, Korea, Republic of
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Status: Active, not recruiting
Seoul, Jongno-gu, Korea, Republic of
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Status: Active, not recruiting
Lisbon, 1649-035, Portugal
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Status: Recruiting
Porto, 4200-072, Portugal
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Status: Recruiting
Torrejon, 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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Status: Recruiting
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