Clinical trial NCT05086692: A Beta-only IL-2 ImmunoTherapY Study
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: 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
Viral Cancer
Cervical Cancers
Endometrial Cancer
Keywords: 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
PDAC
Lead sponsor: Medicenna Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-10-21
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Sequential dose escalation (MDNA11 monotherapy and MDNA11 + pembrolizumab) followed by dose expansion with MDNA11 monotherapy and combination (MDNA11 + pembrolizumab).
Primary purpose: TREATMENT

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.

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: 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.

Primary outcomes:
measure: MDNA11 Recommended Dose for Expansion for monotherapy (mRDE) and Recommended Dose for Expansion for combination (cRDE)
timeFrame: 24 months
measure: Incidence of Treatment Related Adverse Events (TRAEs)
timeFrame: 24 months
measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: 24 months
Secondary outcomes:
measure: Pharmacokinetic characteristics on MDNA11 - Cmax (ug/mL)
timeFrame: Up to 24 months
measure: Pharmacokinetic characteristics on MDNA11 - Tmax (h)
timeFrame: Up to 24 months
measure: Pharmacokinetic characteristics on MDNA11 - AUClast (h.ug/mL)
timeFrame: Up to 24 months
measure: Immunogenicity of MDNA11 (anti-drug antibodies)
timeFrame: Up to 24 months
measure: Pharmacodynamic effects of MDNA11
timeFrame: Up to 24 months
measure: Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Overall Response Rate (ORR)
timeFrame: Approximately 24 months
measure: Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Disease Control Rate (DCR)
timeFrame: Approximately 24 months
measure: Anti-tumor activity of MDNA11 (alone or in combination with CPI) - Progression Free Survival (PFS)
timeFrame: Approximately 24 months
Other outcomes:
measure: Analysis of immune characteristics of the tumor microenvironment
timeFrame: Up to 24 months
Locations:
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: Providence Saint John's Health Center
state: California
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory - Winship Cancer Institute
state: Georgia
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Randwick
country: Australia
facility: Scientia Clinical Research
state: New South Wales
city: Sydney
country: Australia
facility: Macquarie University
state: New South Wales
city: Buderim
country: Australia
facility: University of the Sunshine Coast
state: Queensland
city: Greenslopes
country: Australia
facility: Gallipoli Medical Research Foundation
state: Queensland
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-gu
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea St. Vincent Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Jongno-gu
city: Lisbon
country: Portugal
facility: START Lisbon - Centro de Ensaios Clínicos, ULS Sta Maria
city: Barcelona
country: Spain
facility: START Barcelona / HM Nou Delfos
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: START Madrid / Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Hm Sanchinarro
city: Torrejon
country: Spain
facility: Hospital Universitario de Torrejon
Study officials:
affiliation: Medicenna Therapeutics
name: Nina Merchant
role: STUDY_DIRECTOR
affiliation: Medicenna Therapeutics
name: Arash Yavari, MBBS
role: STUDY_CHAIR
References: