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IO-202 as Monotherapy and IO-202 Plus Azacitidine ± Venetoclax in Patients in AML and CMML

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ClinicalTrials.gov Identifier: NCT04372433
Recruitment Status : Recruiting
First Posted : May 4, 2020
Last Update Posted : February 21, 2023
Sponsor:
Collaborator:
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Immune-Onc Therapeutics

Study Description
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Brief Summary:
To assess safety and tolerability at increasing dose levels of IO-202 in successive cohorts of participants with AML with monocytic differentiation and CMML in order to estimate the maximum tolerated dose (MTD) or maximum administered dose (MAD) and select the recommended Phase 2 dose (RP2D)

Condition or disease Intervention/treatment Phase
AML With Monocytic Differentiation CMML Biological: IO-202 Biological: IO-202 and Azacitidine Biological: IO-202 and Azacitidine + Venetoclax Phase 1

Detailed Description:
This is a Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Intravenously Administered IO-202 and IO-202 + Azacitidine ± Venetoclax in Acute Myeloid Leukemia (AML) Patients with Monocytic Differentiation and in Chronic Myelomonocytic Leukemia (CMML) Patients
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 122 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose Escalation and Expansion
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Intravenously Administered IO-202 and IO-202 + Azacitidine ± Venetoclax in Acute Myeloid Leukemia (AML) Patients With Monocytic Differentiation and in Chronic Myelomonocytic Leukemia (CMML) Patients
Actual Study Start Date : September 14, 2020
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : May 31, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose Escalation of IO-202
Dose cohorts treated with intravenous (IV) IO-202 monotherapy in ascending doses.
 Biological: IO-202
IO-202 as monotherapy
Experimental: Dose Escalation of IO-202 Plus Azacitidine
AZA Dose cohorts treated with intravenous (IV) IO-202 in ascending doses plus Azacitidine (IV or SC) on days 1-7 of each 28-day cycle.
 Biological: IO-202 and Azacitidine
IO-202 and azacitidine combination therapy
Other Name: IO-202 and AZA
Experimental: Dose Expansion of IO-202 plus Azacitidine AML
To enroll high LILRB4 expression monocytic AML patients refractory to or relapsed after available therapies known to be active in AML.
 Biological: IO-202 and Azacitidine
IO-202 and azacitidine combination therapy
Other Name: IO-202 and AZA
Experimental: Dose Expansion of IO-202 plus Azacitidine CMML
To enroll hypomethylating-agent naive CMML patients.
 Biological: IO-202 and Azacitidine
IO-202 and azacitidine combination therapy
Other Name: IO-202 and AZA
Experimental: Dose Expansion of IO-202 plus Azacitidine + Venetoclax (Ven)
To enroll newly diagnosed high LILRB4 expression AML patients who are unfit for intensive induction chemotherapy.
 Biological: IO-202 and Azacitidine + Venetoclax
IO-202 and azacitidine + venetoclax combination therapy
Other Name: IO-202 and AZA + Ven


Outcome Measures
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Primary Outcome Measures :
  1. Safety of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence of adverse events. [ Time Frame: From first dose of IO-202 to 30 days following last study treatment ]
    Incidence of adverse events

  2. Safety of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence of adverse events. [ Time Frame: From first dose of IO-202 to 30 days following last study treatment ]
    Severity of adverse events

  3. Tolerability of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence and duration of dose interruptions and dose reductions of study treatment. [ Time Frame: From first dose of IO-202 to 30 days following last study treatment ]
    Incidence dose interruptions and dose reductions


Secondary Outcome Measures :
  1. To characterize the pharmacokinetics (PK) of IO-202 and IO-202 plus azacitidine ± venetoclax and as defined by maximum plasma concentration (Cmax) [ Time Frame: Through study completion, an average of 1 year ]
    Maximum concentration (Cmax) of IO-202

  2. To characterize the PK of IO-202 and IO-202 IO-202 plus azacitidine ± venetoclax as defined by area under the curve (AUC) [ Time Frame: Through study completion, an average of 1 year ]
    measure area under the curve (AUC) of IO-202

  3. To evaluate the incidence of anti-drug antibodies against IO-202 [ Time Frame: Through study completion, an average of 1 year ]
    Measure anti-drug antibodies in plasma.

  4. To measure rates of response to IO-202 and IO-202 plus azacitidine ± venetoclax [ Time Frame: Through study completion, an average of 1 year ]
    Measure response rates in patients with anti-drug antibodies.


Other Outcome Measures:
  1. To correlate target expression with response rates [ Time Frame: Through study completion, an average of 1 year ]
    Statistical correlation levels of target expression on leukemic blasts with response rate

  2. To correlate target expression with rates of adverse events [ Time Frame: Through study completion, an average of 1 year ]
    Statistical correlation of target expression on leukemic blasts with adverse event rates

  3. To evaluate immunophenotype of leukemic blasts after study treatment. [ Time Frame: Through study completion, an average of 1 year ]
    Measure immunophenotype of leukemic blasts from bone marrow aspirates after study treatment


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must be ≥18.

  2. For the Part 1 Dose-Escalation Phase, patients must be diagnosed with the following:

    1. Relapsed or refractory AML with myelomonocytic or monoblastic/monocytic differentiation according to the World Health Organization 2016 criteria and has failed treatment with available therapies known to be active for AML.
    2. Relapsed or refractory CMML and has failed treatment with available therapies known to be active for CMML

  3. Part 2 Expansion Phase:

    1. Relapsed or refractory LILRB4high AML with myelomonocytic or monoblastic/monocytic differentiation and has failed treatment with available therapies known to be active for AML.
    2. Hypomethylating-agent naive CMML regardless of LILRB4 expression levels.
    3. Newly diagnosed high LILRB4 expression monocytic AML patients considered to be ineligible for standard induction therapy.
  4. Patients must be amenable to serial BM aspirates/biopsies and peripheral blood sampling during the study.
  5. Patients must be able to understand and willing to sign an informed consent. A legally authorized representative may consent.
  6. Patients must have an ECOG performance status of 0 to 2
  7. Patients must have adequate hepatic function
  8. Patients must have adequate renal function
  9. Patients must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer.
  10. Patients must be off systemic calcineurin inhibitors for at least 4 weeks prior to study drug treatment.
  11. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy.

Exclusion Criteria:

  1. Patients who have previously received a monoclonal antibody therapy targeting LILRB4.
  2. Patients who have undergone HSCT within 60 days of the first dose of IO-202.
  3. Patients who received systemic anti-cancer therapy or radiotherapy <7 days prior to their first day of study drug administration (Hydroxyurea or leukapheresis is allowed up to 24 hours prior to the first dose.
  4. Patients who received an investigational agent <7 days prior to their first day of study drug administration.
  5. Patients for whom potentially curative anti-cancer therapy is available.
  6. Patients who are pregnant or breastfeeding.
  7. Patients with uncontrolled, active infection.
  8. Patients with known hypersensitivity to any of the components of the IO-202 formulation.
  9. Patients with known pulmonary lesions and/or history of pneumonitis or interstitial lung disease.
  10. Active known malignancy.
  11. Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) or left ventricular ejection fraction (LVEF) <40%.
  12. Ongoing cardiac dysrhythmias Grade 2 or higher per of NCI CTCAE, Version 5.0, Grade ≥2.
  13. Known or suspected hypersensitivity to recombinant proteins.
  14. Known active bacterial, viral, and/or fungal infection.
  15. Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol.
  16. Patients with clinical signs and/or symptoms suggesting active, uncontrolled central nervous system (CNS) leukemia or known active, uncontrolled CNS leukemia.
  17. Patients with immediately life-threatening, severe complications of leukemia.
  18. Donor Lymphocyte Infusion within 30 days prior to first IO-202 administration.
  19. Current active treatment in another interventional therapeutic clinical study.
  20. Chronic systemic corticosteroid treatment with a dose of >10 mg prednisone/day or dose equivalent.
  21. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
  22. Acute Promyelocytic Leukemia patients or patients with known Philadelphia chromosome (Ph+) positive AML or chronic myelogenous leukemia (CML) blast crisis.
  23. Hyperleukocytosis (leukocytes ≥25 x 10e9/L) at first dose of IO-202.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04372433


Contacts
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Contact: Yasuhiro Tabata, MD, PhD 650-457-1741 yasuhiro.tabata@immuneonc.com
Contact: Kristin Gibbons kristin.gibbons@immuneonc.com

Locations
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United States, California
University California, Davis (117) Recruiting
Davis, California, United States, 95817
City of Hope (106) Recruiting
Duarte, California, United States, 91010
University of California, Irvine (107) Recruiting
Irvine, California, United States, 92868
Stanford University (114) Recruiting
Palo Alto, California, United States, 94305
University of California, San Francisco (118) Recruiting
San Francisco, California, United States, 94143
United States, Colorado
University of Colorado, Anschutz Medical Campus (103) Recruiting
Aurora, Colorado, United States, 80045
United States, Georgia
Winship Cancer Institute of Emory University (105) Recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
The University of Chicago (113) Recruiting
Chicago, Illinois, United States, 60637
United States, New York
Weill Cornell Medical College, New York Presbyterian Hospital (110) Recruiting
New York, New York, United States, 10021
United States, Texas
University of Texas Southwestern, Simmons Comprehensive Cancer Center (104) Recruiting
Dallas, Texas, United States, 75390
MD Anderson Cancer Center (101) Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Immune-Onc Therapeutics
California Institute for Regenerative Medicine (CIRM)
Investigators
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Study Director: Yasuhiro Tabata, MD, PhD Immune-Onc Therapeutics
More Information
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Responsible Party: Immune-Onc Therapeutics
ClinicalTrials.gov Identifier: NCT04372433    
Other Study ID Numbers: IO-202-CL-001
First Posted: May 4, 2020    Key Record Dates
Last Update Posted: February 21, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Immune-Onc Therapeutics:
Monocytic
Additional relevant MeSH terms:
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Azacitidine
Venetoclax
Antimetabolites, Antineoplastic
Antimetabolites
 Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors