A Beta-only IL-2 ImmunoTherapY Study

Ovarian Cancer Clinical Trial

— ABILITY-1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05086692
• Other study ID #: MDNA11-01
• Secondary ID: KEYNOTE-E53MK347
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 27, 2021
• Est. completion date: December 30, 2026

Study information

• Verified date: March 2024
• Source: Medicenna Therapeutics, Inc.
• Contact: Nina Merchant
• Phone: 604-340-3081
• Email: nmerchant[@]medicenna.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 115
• Est. completion date: December 30, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acral Melanoma
• Advanced Solid Tumor
• Basal Cell Carcinoma
• Bladder Cancer
• Carcinoma
• Carcinoma, Basal Cell
• Carcinoma, Merkel Cell
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Ovarian Epithelial
• Carcinoma, Renal Cell
• Carcinoma, Squamous Cell
• Cervical Cancer
• Clear Cell Renal Cell Carcinoma
• Cutaneous Melanoma
• Cutaneous Squamous Cell Carcinoma
• Endometrial Carcinoma
• Endometrial Neoplasms
• Epithelial Ovarian Carcinoma
• Esophageal Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Gastric Cancer
• Lung Neoplasms
• Melanoma
• Merkel Cell Carcinoma
• Mesothelioma
• MSI-H Solid Malignant Tumor
• Mucosal Melanoma
• Neoplasms
• Ovarian Cancer
• Pleural Mesothelioma
• Primary Peritoneal Cancer
• Skin Cancer
• Solid Tumor
• Solid Tumor, Adult
• Squamous Cell Carcinoma of Head and Neck
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

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).
• 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).

Locations

Country	Name	City	State
Australia	Gallipoli Medical Research Foundation	Greenslopes	Queensland
Australia	Scientia Clinical Research	Randwick	New South Wales
Australia	Macquarie University	Sydney	New South Wales
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Samsung Medical Center	Seoul	Gangnam-gu
Korea, Republic of	Seoul National University Hospital	Seoul	Jongno-gu
Korea, Republic of	The Catholic University of Korea St. Vincent Hospital	Suwon-si	Gyeonggi-do
United States	Emory - Winship Cancer Institute	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	MD Anderson Cancer Center	Houston	Texas
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Providence Saint John's Health Center	Santa Monica	California

Sponsors (2)

Lead Sponsor	Collaborator
Medicenna Therapeutics, Inc.	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Analysis of immune characteristics of the tumor microenvironment	Measured by change in Tumor Infiltrating Lymphocyte (TIL) levels	Up to 24 months
Primary	MDNA11 Recommended Dose for Expansion for monotherapy (mRDE) and Recommended Dose for Expansion for combination (cRDE)	Evaluation of tolerability as measured by number of patients with dose limiting toxicities (DLTs)	24 months
Primary	Incidence of Treatment Related Adverse Events (TRAEs)	Rate of TRAEs in patients with advanced solid tumors	24 months
Primary	Incidence of Treatment Emergent Adverse Events (TEAEs)	Rate of TEAEs in patients with advanced solid tumors	24 months
Secondary	Pharmacokinetic characteristics on MDNA11 - Cmax (ug/mL)	Maximum observed serum drug concentration	Up to 24 months
Secondary	Pharmacokinetic characteristics on MDNA11 - Tmax (h)	Time to maximum observed serum drug concentration	Up to 24 months
Secondary	Pharmacokinetic characteristics on MDNA11 - AUClast (h.ug/mL)	Area under the serum concentration vs time curve from time zero to the last measurable concentration	Up to 24 months
Secondary	Immunogenicity of MDNA11 (anti-drug antibodies)	Incidence and persistence of anti-drug antibodies to MDNA11	Up to 24 months
Secondary	Pharmacodynamic effects of MDNA11	Measurement of translational parameters - Flow cytometry analysis of immune cells in blood and serum measurements of cytokine levels	Up to 24 months
Secondary	Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Overall Response Rate (ORR)	Assessed by RECIST v1.1 and iRECIST; CR+PR/Evaluable N	Approximately 24 months
Secondary	Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Disease Control Rate (DCR)	CR+PR+SD/Evaluable N	Approximately 24 months
Secondary	Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Progression Free Survival (PFS)	Time from signing ICF to disease progression	Approximately 24 months