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NCT05086692PHASE1, PHASE2Recruiting

A Beta-only IL-2 ImmunoTherapY Study

Medicenna Therapeutics, Inc.

Start Date

8/27/2021

Completion Date

12/30/2026

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.

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

MDNA11

DRUG

Pembrolizumab (KEYTRUDA®)

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Conditions

Advanced Solid TumorUnresectable Solid TumorClear Cell Renal Cell CarcinomaTriple Negative Breast CancerNon-Small Cell Lung Cancer SquamousNon-Small Cell Lung Cancer Non-squamousColorectal Cancer (MSI-H)Gastric CancerCervical CancerBasal Cell CarcinomaBladder CancerMerkel Cell CarcinomaSquamous Cell Carcinoma of Head and NeckCutaneous Squamous Cell CarcinomaPleural MesotheliomaEsophageal CancerEndometrial CarcinomaSolid TumorSolid Tumor, AdultMSI-H Solid Malignant TumorCancer With A High Tumor Mutational BurdenEpithelial Ovarian CarcinomaPrimary Peritoneal CancerGastroesophageal Junction (GEJ) CancerAcral MelanomaMucosal MelanomaCutaneous MelanomaDMMR Solid Malignant TumorFallopian Tube CancerOvarian CancerMSI-H CancerDMMR CancerPancreas Adenocarcinoma (MSI-H)Skin CancerViral CancerCervical CancersEndometrial Cancer

Locations

Sharp Memorial Hospital

San Diego, California 92123

United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California 94158

United States

Providence Saint John's Health Center

Santa Monica, California 90404

United States

Boca Raton Regional Hospital

Boca Raton, Florida 33486

United States

Emory - Winship Cancer Institute

Atlanta, Georgia 30322

United States

Karmanos Cancer Institute

Detroit, Michigan 48201

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Scientia Clinical Research

Randwick, New South Wales 2031

Australia

Macquarie University

Sydney, New South Wales 2109

Australia

University of the Sunshine Coast

Buderim, Queensland 4556

Australia

Gallipoli Medical Research Foundation

Greenslopes, Queensland 4120

Australia

Princess Margaret Cancer Center

Toronto, Ontario M4W 3E2

Canada

Mater Misericordiae University Hospital

Dublin, D07 R2WY

Ireland

START Lisbon - Centro de Ensaios Clínicos, ULS Sta Maria

Lisbon, 1649-035

Portugal

Instituto Portugues De Oncologia Do Porto

Porto, 4200-072

Portugal

Samsung Medical Center

Seoul, Gangnam-gu

South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do

South Korea

The Catholic University of Korea St. Vincent Hospital

Suwon, Gyeonggi-do

South Korea

Seoul National University Hospital

Seoul, Jongno-gu

South Korea

Institut Catala d'Oncologia (ICO)-Badalona

Badalona, 08916

Spain

START Barcelona / HM Nou Delfos

Barcelona, 08023

Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041

Spain

Hospital Universitario Ramón y Cajal

Madrid, 28034

Spain

START Madrid / Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040

Spain

Hospital Universitario Hm Sanchinarro

Madrid, 28050

Spain

Hospital Universitario Central de Asturias (HUCA)

Oviedo, 33011

Spain

Hospital Universitario de Torrejon

Torrejón, 28850

Spain