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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 : March 15, 2024
Sponsor:
Collaborator:
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Immune-Onc Therapeutics

Tracking Information
First Submitted Date  ICMJE April 20, 2020
First Posted Date  ICMJE May 4, 2020
Last Update Posted Date March 15, 2024
Actual Study Start Date  ICMJE September 14, 2020
Estimated Primary Completion Date January 31, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 17, 2023)
  • 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
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: April 29, 2020)
  • Safety of IO-202 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
  • Safety of IO-202 as measured by severity of adverse events. [ Time Frame: From first dose of IO-202 to 30 days following last study treatment ]
    Severity of adverse events
  • Tolerability of IO-202 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2023)
  • 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
  • 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
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2020)
  • To characterize the pharmacokinetics (PK) of IO-202 as defined by maximum plasma concentration (Cmax) [ Time Frame: Through study completion, an average of 1 year ]
    Maximum concentration (Cmax) of IO-202
  • To characterize the PK of IO-202 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
  • 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.
  • To measure rates of response to IO-202 in patients with anti-drug antibodies [ Time Frame: Through study completion, an average of 1 year ]
    Measure response rates in patients with anti-drug antibodies.
  • Measure response rates in patients treated with IO-202 or IO-202 in combination with AZA [ Time Frame: Through study completion, an average of 1 year ]
    Measure response rates by bone marrow examination of blast percentage.
Current Other Pre-specified Outcome Measures
 (submitted: May 3, 2022)
  • 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
  • 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
  • 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
Original Other Pre-specified Outcome Measures
 (submitted: April 29, 2020)
  • To assess changes in lymphocytes with IO-202 or IO-202 in combination with AZA [ Time Frame: Through study completion, a average of 1 year ]
    Measure changes in numbers of lymphocytes with study drug treatment
  • To measure blood immune proteins with IO-202 or IO-202 in combination with AZA [ Time Frame: Through study completion, a average of 1 year ]
    Measure changes in blood immune proteins with study drug treatment
  • To correlate target expression with response rates [ Time Frame: Through study completion, a average of 1 year ]
    Statistical correlation levels of target expression on leukemic blasts with response rate
  • To correlate target expression with rates of adverse events [ Time Frame: Through study completion, a average of 1 year ]
    Statistical correlation of target expression on leukemic blasts with adverse event rates
  • To evaluate immunophenotype of leukemic blasts after study treatment. [ Time Frame: Through study completion, a average of 1 year ]
    Measure immunophenotype of leukemic blasts from bone marrow aspirates after study treatment
 
Descriptive Information
Brief Title  ICMJE IO-202 as Monotherapy and IO-202 Plus Azacitidine ± Venetoclax in Patients in AML and CMML
Official Title  ICMJE 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
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)
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Dose Escalation and Expansion
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • AML With Monocytic Differentiation
  • CMML
Intervention  ICMJE
  • Biological: IO-202
    IO-202 as monotherapy
  • Biological: IO-202 and Azacitidine
    IO-202 and azacitidine combination therapy
    Other Name: IO-202 and AZA
  • Biological: IO-202 and Azacitidine + Venetoclax
    IO-202 and azacitidine + venetoclax combination therapy
    Other Name: IO-202 and AZA + Ven
Study Arms  ICMJE
  • Experimental: Dose Escalation of IO-202
    Dose cohorts treated with intravenous (IV) IO-202 monotherapy in ascending doses.
    Intervention: Biological: IO-202
  • 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.
    Intervention: Biological: IO-202 and Azacitidine
  • 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.
    Intervention: Biological: IO-202 and Azacitidine
  • Experimental: Dose Expansion of IO-202 plus Azacitidine CMML
    To enroll hypomethylating-agent naive CMML patients.
    Intervention: Biological: IO-202 and Azacitidine
  • 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.
    Intervention: Biological: IO-202 and Azacitidine + Venetoclax
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 6, 2023)		 106
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2020)		 64
Estimated Study Completion Date  ICMJE January 31, 2027
Estimated Primary Completion Date January 31, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yasuhiro Tabata, MD, PhD 650-457-1741 yasuhiro.tabata@immuneonc.com
Contact: Kristin Gibbons kristin.gibbons@immuneonc.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04372433
Other Study ID Numbers  ICMJE IO-202-CL-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Immune-Onc Therapeutics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Immune-Onc Therapeutics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE California Institute for Regenerative Medicine (CIRM)
Investigators  ICMJE
Study Director: Yasuhiro Tabata, MD, PhD Immune-Onc Therapeutics
PRS Account Immune-Onc Therapeutics
Verification Date March 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP