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

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

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)

Study Overview

• Status: Completed
• Conditions: CMML; AML With Monocytic Differentiation
• Intervention / Treatment: Biological: IO-202; Biological: IO-202 and Azacitidine; Biological: IO-202 and Azacitidine + Venetoclax

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: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Davis, California, United States, 95817
      • University California, Davis (117)
    • Duarte, California, United States, 91010
      • City of Hope (106)
    • Irvine, California, United States, 92868
      • University of California, Irvine (107)
    • Los Angeles, California, United States, 90095
      • UCLA, Medical Center Division of Hematology/Oncology (119)
    • Palo Alto, California, United States, 94305
      • Stanford University (114)
    • San Francisco, California, United States, 94143
      • University of California, San Francisco (118)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado, Anschutz Medical Campus (103)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University (105)
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago (113)
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College, New York Presbyterian Hospital (110)
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic, Taussig Cancer Institute (111)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University, Center for Hematologic Malignancies (116)
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern, Simmons Comprehensive Cancer Center (104)
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center (101)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: 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 Names: IO-202 and AZA + Ven

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence of adverse events.	Incidence of adverse events	From first dose of IO-202 to 30 days following last study treatment
Safety of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence of adverse events.	Severity of adverse events	From first dose of IO-202 to 30 days following last study treatment
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.	Incidence dose interruptions and dose reductions	From first dose of IO-202 to 30 days following last study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the incidence of anti-drug antibodies against IO-202	Measure anti-drug antibodies in plasma.	Through study completion, an average of 1 year
To characterize the pharmacokinetics (PK) of IO-202 and IO-202 plus azacitidine ± venetoclax and as defined by maximum plasma concentration (Cmax)	Maximum concentration (Cmax) of IO-202	Through study completion, an average of 1 year
To characterize the PK of IO-202 and IO-202 IO-202 plus azacitidine ± venetoclax as defined by area under the curve (AUC)	measure area under the curve (AUC) of IO-202	Through study completion, an average of 1 year
To measure rates of response to IO-202 and IO-202 plus azacitidine ± venetoclax	Measure response rates in patients with anti-drug antibodies.	Through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To correlate target expression with response rates	Statistical correlation levels of target expression on leukemic blasts with response rate	Through study completion, an average of 1 year
To correlate target expression with rates of adverse events	Statistical correlation of target expression on leukemic blasts with adverse event rates	Through study completion, an average of 1 year
To evaluate immunophenotype of leukemic blasts after study treatment.	Measure immunophenotype of leukemic blasts from bone marrow aspirates after study treatment	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Immune-Onc Therapeutics
• Collaborators: California Institute for Regenerative Medicine (CIRM)
• Investigators: Study Director: Hong Xiang, PhD, Immune-Onc Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Actual): January 31, 2025
• Study Completion (Actual): January 31, 2025

Study Registration Dates

• First Submitted: April 20, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (Actual): May 4, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 13, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Monocytic
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myelodysplastic-Myeloproliferative Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Venetoclax; Azacitidine
• Other Study ID Numbers: IO-202-CL-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No