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

• ClinicalTrials.gov Identifier: NCT05086692
• Recruitment Status: Recruiting
• First Posted: October 21, 2021
• Last Update Posted: November 3, 2022
• Sponsor: Medicenna Therapeutics, Inc.
• 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; Melanoma; Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; Triple Negative Breast Cancer; Cutaneous Melanoma; Non-Small Cell Lung Cancer Squamous; Non-Small Cell Lung Cancer Non-squamous; Colorectal Cancer; Gastric Cancer; Biliary Tract Cancer; Gallbladder 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; Hepatocellular Carcinoma; Endometrial Carcinoma; Solid Tumor; Solid Tumor, Adult	Drug: MDNA11 Monotherapy; Drug: MDNA11 in combination with checkpoint inhibitor	Phase 1; Phase 2

Detailed Description:

The study drug, MDNA11, is a selective IL-2 preferentially activating effector T cells (naïve CD8+ T-cells) and NK cells responsible for killing cancer cells, with minimal or no stimulation of the 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 16 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 two parts:

• Sequential Dose Escalation
• Dose Expansion in monotherapy as well as with an immune checkpoint inhibitor.

Approximately 100 patients will be enrolled.

Tumor assessment by CT/MRI will be performed every 12 weeks and will continue until documented disease progression. Treatment may continue for up to 1 year, or until treatment discontinuation criteria are met. Patients can withdraw from participation at any time.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: Sequential dose escalation (MDNA11 monotherapy) followed by dose expansion with MDNA11 monotherapy as well as in combination with a CPI.
• 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: September 30, 2024
• Estimated Study Completion Date: December 30, 2024

Arms and Interventions

Arm

Intervention/treatment

Experimental: MDNA11; MDNA11 is a long-acting "beta-only" recombinant interleukin-2 (rIL-2) albumin fusion

Drug: MDNA11 Monotherapy; MDNA11 will be administered by the IV route 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 Recommended Phase 2 Dose (RP2D); Other Name: Interleukin-2 (IL-2)-albumin; Drug: MDNA11 in combination with checkpoint inhibitor; MDNA11 in combination with checkpoint inhibitor Combination cohort is planned to evaluate the safety/ tolerability and anti-tumor activity of single agent MDNA11, or in combination with CPI in patients with solid tumors; Other Name: Interleukin-2 (IL-2)-albumin with checkpoint inhibitor

Outcome Measures

Primary Outcome Measures :

1. Recommended Phase 2 Dose (RP2D) for MDNA11 [ Time Frame: 12 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: 12 months ]
   Rate of TRAEs in patients with advanced solid tumors
3. Incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 12 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 12 months ]
   Maximum observed serum drug concentration
2. Pharmacokinetic characteristics on MDNA11 - Tmax (h) [ Time Frame: Up to 12 months ]
   Time to maximum observed serum drug concentration
3. Pharmacokinetic characteristics on MDNA11 - AUClast (h.ug/mL) [ Time Frame: Up to 12 months ]
   Area under the serum concentration vs time curve from time zero to the last measurable concentration
4. Pharmacodynamic effects of MDNA11 [ Time Frame: Up to 12 months ]
   Measurement of translational parameters - Flow cytometry analysis of immune cells in blood and serum measurements of cytokine levels
5. Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Overall Response Rate (ORR) [ Time Frame: Approximately 12 months ]
   Assessed by RECIST v1.1; CR+PR/Evaluable N
6. Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Disease Control Rate (DCR) [ Time Frame: Approximately 12 months ]
   CR+PR+SD/Evaluable N
7. Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Progression Free Survival (PFS) [ Time Frame: Approximately 12 months ]
   Time from signing ICF to disease progression

Other Outcome Measures:

1. Analysis of immune characteristics of the tumor microenvironment [ Time Frame: Up to 12 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 that is unresectable (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 or any investigational treatment within 28 days or less than 5 times the half-life, whichever is shorter. Palliative radiotherapy given within 28 days prior to the first dose of study drug may be approved on a case-by-case basis in discussion with the Sponsor.
2. Has carcinomatous meningitis or leptomeningeal disease; stable CNS metastases permitted based on Medical Monitor review.
3. Active malignancy (other than the disease under treatment in the study) within the previous 3 years except for curable cancers
4. Clinically significant active, known or suspected autoimmune disease, or diseases that can be exacerbated with immunotherapy.
5. Severe pulmonary, cardiac or other systemic disease.
6. Females who are pregnant or lactating or planning to become pregnant during the study.
7. Active infection requiring systemic therapy.
8. Any medical, emotional or psychiatric condition that interfere with the patient's ability to adhere to the protocol
9. 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.
10. Known severe hypersensitivity to any component of study drug(s).
11. Prior Interleukin therapy.
12. 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

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

Australia, New South Wales

Chris O'Brien Lifehouse; Recruiting

Camperdown, New South Wales, Australia, 2050

Scientia Clinical Research; Recruiting

Randwick, New South Wales, Australia, 2031

Australia, Queensland

Gallipoli Medical Research Foundation; Recruiting

Greenslopes, Queensland, Australia, 4120

Canada, Ontario

Princess Margaret Cancer Center; Recruiting

Toronto, Ontario, Canada, M4W 3E2

Sponsors and Collaborators

Medicenna Therapeutics, Inc.

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
• First Posted: October 21, 2021
• Last Update Posted: November 3, 2022
• Last Verified: October 2022

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; RCC; 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

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; Carcinoma, Basal Cell; Biliary Tract Neoplasms; Endometrial Neoplasms; Gallbladder Neoplasms; 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; Digestive System Neoplasms; Digestive System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue