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

• ClinicalTrials.gov Identifier: NCT05086692
• Recruitment Status: Recruiting
• First Posted: October 21, 2021
• Last Update Posted: March 29, 2024
• Sponsor: Medicenna Therapeutics, Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Medicenna Therapeutics, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor; Unresectable Solid Tumor; Clear Cell Renal Cell Carcinoma; Triple Negative Breast Cancer; Non-Small Cell Lung Cancer Squamous; Non-Small Cell Lung Cancer Non-squamous; Colorectal Cancer (MSI-H); Gastric Cancer; Cervical Cancer; Basal Cell Carcinoma; Bladder Cancer; Merkel Cell Carcinoma; Squamous Cell Carcinoma of Head and Neck; Cutaneous Squamous Cell Carcinoma; Pleural Mesothelioma; Esophageal Cancer; Endometrial Carcinoma; Solid Tumor; Solid Tumor, Adult; MSI-H Solid Malignant Tumor; Cancer With A High Tumor Mutational Burden; Epithelial Ovarian Carcinoma; Primary Peritoneal Cancer; Gastroesophageal Junction (GEJ) Cancer; Acral Melanoma; Mucosal Melanoma; Cutaneous Melanoma; DMMR Solid Malignant Tumor; Fallopian Tube Cancer; Ovarian Cancer; MSI-H Cancer; DMMR Cancer; Pancreas Adenocarcinoma (MSI-H); Skin Cancer	Drug: MDNA11; Drug: Pembrolizumab	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 115 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: Sequential dose escalation (MDNA11 monotherapy and MDNA11 + pembrolizumab) followed by dose expansion with MDNA11 monotherapy and combination (MDNA11 + pembrolizumab).
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 27, 2021
• Estimated Primary Completion Date: June 30, 2026
• Estimated Study Completion Date: December 30, 2026

Arms and Interventions

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 Name: Interleukin-2 (IL-2)-albumin; Drug: Pembrolizumab; 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).

Outcome Measures

Primary Outcome Measures :

1. 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)
2. Incidence of Treatment Related Adverse Events (TRAEs) [ Time Frame: 24 months ]
   Rate of TRAEs in patients with advanced solid tumors
3. Incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 24 months ]
   Rate of TEAEs in patients with advanced solid tumors

Secondary Outcome Measures :

1. Pharmacokinetic characteristics on MDNA11 - Cmax (ug/mL) [ Time Frame: Up to 24 months ]
   Maximum observed serum drug concentration
2. Pharmacokinetic characteristics on MDNA11 - Tmax (h) [ Time Frame: Up to 24 months ]
   Time to maximum observed serum drug concentration
3. 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
4. Immunogenicity of MDNA11 (anti-drug antibodies) [ Time Frame: Up to 24 months ]
   Incidence and persistence of anti-drug antibodies to MDNA11
5. 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
6. 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
7. 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
8. 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

Other Outcome Measures:

1. Analysis of immune characteristics of the tumor microenvironment [ Time Frame: Up to 24 months ]
   Measured by change in Tumor Infiltrating Lymphocyte (TIL) levels

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Male Female (Women of Childbearing Potential will be subject to pregnancy testing)
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Nina Merchant; 604-340-3081; nmerchant@medicenna.com

Contact: Melissa Coello; 267-476-2313; mcoello@medicenna.com

Locations

United States, California

UCSF Helen Diller Family Comprehensive Cancer Center; Recruiting

San Francisco, California, United States, 94158

Providence Saint John's Health Center; Recruiting

Santa Monica, California, United States, 90404

United States, Florida

Boca Raton Regional Hospital; Recruiting

Boca Raton, Florida, United States, 33486

Orlando Health Cancer Institute; Recruiting

Orlando, Florida, United States, 32806

United States, Georgia

Emory - Winship Cancer Institute; Recruiting

Atlanta, Georgia, United States, 30322

United States, Maryland

Johns Hopkins Hospital; Not yet recruiting

Baltimore, Maryland, United States, 21287

United States, Michigan

Karmanos Cancer Institute; Recruiting

Detroit, Michigan, United States, 48201

United States, Texas

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Australia, New South Wales

Scientia Clinical Research; Recruiting

Randwick, New South Wales, Australia, 2031

Macquarie University; Recruiting

Sydney, New South Wales, Australia, 2109

Australia, Queensland

Gallipoli Medical Research Foundation; Recruiting

Greenslopes, Queensland, Australia, 4120

Canada, Ontario

Princess Margaret Cancer Center; Recruiting

Toronto, Ontario, Canada, M4W 3E2

Korea, Republic of

Samsung Medical Center; Recruiting

Seoul, Gangnam-gu, Korea, Republic of

Seoul National University Bundang Hospital; Recruiting

Seongnam-si, Gyeonggi-do, Korea, Republic of

The Catholic University of Korea St. Vincent Hospital; Recruiting

Suwon-si, Gyeonggi-do, Korea, Republic of

Seoul National University Hospital; Recruiting

Seoul, Jongno-gu, Korea, Republic of

Sponsors and Collaborators

Medicenna Therapeutics, Inc.

Merck Sharp & Dohme LLC

Investigators

• Study Director: Nina Merchant; Medicenna Therapeutics
• Study Chair: Martin Bexon, MBBS; Medicenna Therapeutics

More Information

• Responsible Party: Medicenna Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05086692
• Other Study ID Numbers: MDNA11-01; KEYNOTE-E53 ( Other Identifier: Merck Sharp & Dohme, LLC ); MK3475-E53 ( Other Identifier: Merck Sharp & Dohme, LLC )
• First Posted: October 21, 2021
• Last Update Posted: March 29, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Medicenna Therapeutics, Inc.:

IL-2; IL2; Interleukin-2; cancer; metastatic; ccRCC; TNBC; NSCLC; CRC; GEJ; intrahepatic; extrahepatic; MCC; SCCHN; CSCC; Gastroesophageal Junction; advanced; unresectable; MSI-H; dMMR; Microsatellite Instability-High; Mismatch Repair Deficient; PD-1; immunotherapy; anti-PD-1; BCC; RCC; HCC; Tumor Mutation Burden High; TMB-H

Additional relevant MeSH terms:

Carcinoma, Merkel Cell; Carcinoma; Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma; Carcinoma, Squamous Cell; Carcinoma, Renal Cell; Triple Negative Breast Neoplasms; Mesothelioma; Fallopian Tube Neoplasms; Carcinoma, Basal Cell; Endometrial Neoplasms; Carcinoma, Ovarian Epithelial; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms