A Beta-only IL-2 ImmunoTherapY (ABILITY) Study
Study Details
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 |
|---|---|---|
|
|
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
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 Names:
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 Names:
|
Outcome Measures
Primary Outcome Measures
- Recommended Phase 2 Dose (RP2D) for MDNA11 [12 months]
Evaluation of tolerability as measured by number of patients with dose limiting toxicities (DLTs)
- Incidence of Treatment Related Adverse Events (TRAEs) [12 months]
Rate of TRAEs in patients with advanced solid tumors
- Incidence of Treatment Emergent Adverse Events (TEAEs) [12 months]
Rate of TEAEs in patients with advanced solid tumors
Secondary Outcome Measures
- Pharmacokinetic characteristics on MDNA11 - Cmax (ug/mL) [Up to 12 months]
Maximum observed serum drug concentration
- Pharmacokinetic characteristics on MDNA11 - Tmax (h) [Up to 12 months]
Time to maximum observed serum drug concentration
- Pharmacokinetic characteristics on MDNA11 - AUClast (h.ug/mL) [Up to 12 months]
Area under the serum concentration vs time curve from time zero to the last measurable concentration
- Pharmacodynamic effects of MDNA11 [Up to 12 months]
Measurement of translational parameters - Flow cytometry analysis of immune cells in blood and serum measurements of cytokine levels
- Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Overall Response Rate (ORR) [Approximately 12 months]
Assessed by RECIST v1.1; CR+PR/Evaluable N
- Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Disease Control Rate (DCR) [Approximately 12 months]
CR+PR+SD/Evaluable N
- Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Progression Free Survival (PFS) [Approximately 12 months]
Time from signing ICF to disease progression
Other Outcome Measures
- Analysis of immune characteristics of the tumor microenvironment [Up to 12 months]
Measured by change in Tumor Infiltrating Lymphocyte (TIL) levels
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Aged at least 18 years (inclusive at the time of informed consent).
-
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
-
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.
-
Histologically or cytologically confirmed locally advanced or metastatic solid tumor that is unresectable (see tumor types listed under conditions)
-
Demonstrated adequate organ function
-
Measurable disease as per Response Evaluation Criteria in Solid Tumors, (RECIST v1.1) and documented by CT and/or MRI.
-
Life expectancy of ≥ 12 weeks.
-
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.
-
Agree to use highly effective contraception methods. WOCBP must agree to use highly effective birth control
Key Exclusion Criteria:
-
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.
-
Has carcinomatous meningitis or leptomeningeal disease; stable CNS metastases permitted based on Medical Monitor review.
-
Active malignancy (other than the disease under treatment in the study) within the previous 3 years except for curable cancers
-
Clinically significant active, known or suspected autoimmune disease, or diseases that can be exacerbated with immunotherapy.
-
Severe pulmonary, cardiac or other systemic disease.
-
Females who are pregnant or lactating or planning to become pregnant during the study.
-
Active infection requiring systemic therapy.
-
Any medical, emotional or psychiatric condition that interfere with the patient's ability to adhere to the protocol
-
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.
-
Known severe hypersensitivity to any component of study drug(s).
-
Prior Interleukin therapy.
-
Inability to comply with study and follow up procedures as judged by the Investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Boca Raton Regional Hospital | Boca Raton | Florida | United States | 33486 |
| 2 | Orlando Health Cancer Institute | Orlando | Florida | United States | 32806 |
| 3 | Emory - Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 4 | Chris O'Brien Lifehouse | Camperdown | New South Wales | Australia | 2050 |
| 5 | Scientia Clinical Research | Randwick | New South Wales | Australia | 2031 |
| 6 | Gallipoli Medical Research Foundation | Greenslopes | Queensland | Australia | 4120 |
| 7 | ICON Cancer Center | South Brisbane | Queensland | Australia | 4101 |
| 8 | Princess Margaret Cancer Center | 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MDNA11-01