A Beta-only IL-2 ImmunoTherapY Study (ABILITY-1)

July 3, 2025 updated by: Medicenna Therapeutics, Inc.

A Phase 1/2 Open Label, Dose Escalation and Expansion Study of MDNA11, IL-2 Superkine, Administered Alone or in Combination With Immune Checkpoint Inhibitor in Patients With Advanced Solid Tumors

This is a Phase 1/2, multi-center, open-label, dose-escalation and expansion study to evaluate safety and tolerability, PK, pharmacodynamic, and early signal of anti-tumor activity of MDNA11 alone or in combination with a checkpoint inhibitor in patients with advanced solid tumors.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study drug, MDNA11, long-acting "beta-only" recombinant interleukin-2 (rIL-2). MDNA11 specifically engineered to overcome the shortcomings of rhIL-2 (aldesleukin) by preferentially activating immune effector cells (CD8+ T- and NK cells) responsible for killing cancer cells, with minimal or no stimulation of immunosuppressive Tregs. It is designed to potentially enhance host immune response and fusion to albumin increases the half-life further avoiding frequent dosing required with rhIL-2.

The study will be conducted at up to 30 clinical sites following regulatory authority and institutional review board / independent ethics committee (IRB/ IEC) approval and completion of informed consent. The study will be conducted in multiple parts:

  • Monotherapy (MDNA11 alone) dose escalation
  • Monotherapy (MDNA11 alone) dose expansion in select tumor types
  • Combination (MDNA11 + pembrolizumab) dose escalation
  • Combination (MDNA11 + pembrolizumab) dose expansion in select tumor types

Approximately 115 patients will be enrolled.

After commencing treatment (first exposure of MDNA11 alone or MDNA11 + pembrolizumab), tumor assessment by CT/MRI will be performed every 8 weeks ± 1 week until immune confirmed progressive disease ("iCPD") by iRECIST, discontinuation of study drug(s), withdrawal of consent or loss to follow-up. Treatment beyond progression may be permitted if criteria are met. Patients can withdraw from participation at any time.

Study Type

Interventional

Enrollment (Estimated)

115

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Recruiting
        • Scientia Clinical Research
      • Sydney, New South Wales, Australia, 2109
        • Recruiting
        • Macquarie University
    • Queensland
      • Buderim, Queensland, Australia, 4556
        • Recruiting
        • University of the Sunshine Coast
      • Greenslopes, Queensland, Australia, 4120
        • Recruiting
        • Gallipoli Medical Research Foundation
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4W 3E2
        • Recruiting
        • Princess Margaret Cancer Center
  • Ireland
      • Dublin, Ireland, D07 R2WY
        • Recruiting
        • Mater Misericordiae University Hospital
  • Korea, Republic of
    • Gangnam-gu
      • Seoul, Gangnam-gu, Korea, Republic of
        • Active, not recruiting
        • Samsung Medical Center
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, Korea, Republic of
        • Active, not recruiting
        • Seoul National University Bundang Hospital
      • Suwon-si, Gyeonggi-do, Korea, Republic of
        • Active, not recruiting
        • The Catholic University of Korea St. Vincent Hospital
    • Jongno-gu
      • Seoul, Jongno-gu, Korea, Republic of
        • Active, not recruiting
        • Seoul National University Hospital
  • Portugal
      • Lisbon, Portugal, 1649-035
        • Recruiting
        • START Lisbon - Centro de Ensaios Clínicos, ULS Sta Maria
      • Porto, Portugal, 4200-072
        • Recruiting
        • Instituto Portugues de Oncologia do Porto
  • Spain
      • Badalona, Spain, 08916
        • Recruiting
        • Institut Catala d'Oncologia (ICO)-Badalona
      • Barcelona, Spain, 08041
        • Recruiting
        • Hospital De La Santa Creu I Sant Pau
      • Barcelona, Spain, 08023
        • Recruiting
        • START Barcelona / HM Nou Delfos
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28050
        • Recruiting
        • Hospital Universitario HM Sanchinarro
      • Madrid, Spain, 28040
        • Recruiting
        • START Madrid / Hospital Universitario Fundacion Jimenez Diaz
      • Oviedo, Spain, 33011
        • Recruiting
        • Hospital Universitario Central de Asturias (HUCA)
      • Torrejon, Spain, 28850
        • Recruiting
        • Hospital Universitario de Torrejon
  • United States
    • California
      • San Diego, California, United States, 92123
        • Recruiting
        • Sharp Memorial Hospital
      • San Francisco, California, United States, 94158
        • Active, not recruiting
        • UCSF Helen Diller Family Comprehensive Cancer Center
      • Santa Monica, California, United States, 90404
        • Recruiting
        • Providence Saint John's Health Center
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Recruiting
        • Boca Raton Regional Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory - Winship Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Institute
    • Texas
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • Md Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MDNA11
MDNA11 is a long-acting "beta-only" recombinant interleukin-2 (rIL-2) albumin fusion
Drug: MDNA11
MDNA11 will be administered, IV on a once every 2 weeks (Q2W) dosing schedule. Provisional dose cohorts for monotherapy dose escalation doses ranging from 0.003 to 0.6 (mg/kg): until determining the monotherapy Recommended Dose for Expansion (mRDE).
Other Names:
  • Interleukin-2 (IL-2)-albumin
Drug: Pembrolizumab (KEYTRUDA®)
MDNA11 will be administered in combination with pembrolizumab, IV. MDNA11 dose range to be evaluated in combination with pembrolizumab until determining the combination Recommended Dose for Expansion (cRDE).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment Related Adverse Events (TRAEs)
Time Frame: 24 months
Rate of TRAEs in patients with advanced solid tumors
24 months
Incidence of Treatment Emergent Adverse Events (TEAEs)
Time Frame: 24 months
Rate of TEAEs in patients with advanced solid tumors
24 months
MDNA11 Recommended Dose for Expansion for monotherapy (mRDE) and Recommended Dose for Expansion for combination (cRDE)
Time Frame: 24 months
Evaluation of tolerability as measured by number of patients with dose limiting toxicities (DLTs)
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetic characteristics on MDNA11 - Cmax (ug/mL)
Time Frame: Up to 24 months
Maximum observed serum drug concentration
Up to 24 months
Pharmacokinetic characteristics on MDNA11 - Tmax (h)
Time Frame: Up to 24 months
Time to maximum observed serum drug concentration
Up to 24 months
Pharmacokinetic characteristics on MDNA11 - AUClast (h.ug/mL)
Time Frame: Up to 24 months
Area under the serum concentration vs time curve from time zero to the last measurable concentration
Up to 24 months
Pharmacodynamic effects of MDNA11
Time Frame: Up to 24 months
Measurement of translational parameters - Flow cytometry analysis of immune cells in blood and serum measurements of cytokine levels
Up to 24 months
Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Overall Response Rate (ORR)
Time Frame: Approximately 24 months
Assessed by RECIST v1.1 and iRECIST; CR+PR/Evaluable N
Approximately 24 months
Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Disease Control Rate (DCR)
Time Frame: Approximately 24 months
CR+PR+SD/Evaluable N
Approximately 24 months
Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Progression Free Survival (PFS)
Time Frame: Approximately 24 months
Time from signing ICF to disease progression
Approximately 24 months
Immunogenicity of MDNA11 (anti-drug antibodies)
Time Frame: Up to 24 months
Incidence and persistence of anti-drug antibodies to MDNA11
Up to 24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Analysis of immune characteristics of the tumor microenvironment
Time Frame: Up to 24 months
Measured by change in Tumor Infiltrating Lymphocyte (TIL) levels
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medicenna Therapeutics, Inc.

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Nina Merchant, Medicenna Therapeutics
  • Study Chair: Arash Yavari, MBBS, Medicenna Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 27, 2021

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

December 30, 2026

Study Registration Dates

First Submitted

September 10, 2021

First Submitted That Met QC Criteria

October 7, 2021

First Posted (Actual)

October 21, 2021

Study Record Updates

Last Update Posted (Actual)

July 9, 2025

Last Update Submitted That Met QC Criteria

July 3, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MDNA11-01
  • KEYNOTE-E53 (Other Identifier: Merck Sharp & Dohme, LLC)
  • MK3475-E53 (Other Identifier: Merck Sharp & Dohme, LLC)
  • 2023-507536-21-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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