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
1 other identifier
interventional
67
1 country
14
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)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2020
Longer than P75 for phase_1
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 20, 2020
CompletedFirst Posted
Study publicly available on registry
May 4, 2020
CompletedStudy Start
First participant enrolled
September 14, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 31, 2025
CompletedFebruary 14, 2025
February 1, 2025
4.4 years
April 20, 2020
February 13, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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 Outcomes (4)
To characterize the pharmacokinetics (PK) of IO-202 and IO-202 plus azacitidine ± venetoclax and as defined by maximum plasma concentration (Cmax)
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)
Through study completion, an average of 1 year
To evaluate the incidence of anti-drug antibodies against IO-202
Through study completion, an average of 1 year
To measure rates of response to IO-202 and IO-202 plus azacitidine ± venetoclax
Through study completion, an average of 1 year
Other Outcomes (3)
To correlate target expression with response rates
Through study completion, an average of 1 year
To correlate target expression with rates of adverse events
Through study completion, an average of 1 year
To evaluate immunophenotype of leukemic blasts after study treatment.
Through study completion, an average of 1 year
Study Arms (5)
Dose Escalation of IO-202
EXPERIMENTALDose cohorts treated with intravenous (IV) IO-202 monotherapy in ascending doses.
Dose Escalation of IO-202 Plus Azacitidine
EXPERIMENTALAZA 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.
Dose Expansion of IO-202 plus Azacitidine AML
EXPERIMENTALTo enroll high LILRB4 expression monocytic AML patients refractory to or relapsed after available therapies known to be active in AML.
Dose Expansion of IO-202 plus Azacitidine CMML
EXPERIMENTALTo enroll hypomethylating-agent naive CMML patients.
Dose Expansion of IO-202 plus Azacitidine + Venetoclax (Ven)
EXPERIMENTALTo enroll newly diagnosed high LILRB4 expression AML patients who are unfit for intensive induction chemotherapy.
Interventions
IO-202 and azacitidine combination therapy
IO-202 and azacitidine + venetoclax combination therapy
Eligibility Criteria
You may qualify if:
- Patients must be ≥18.
- For the Part 1 Dose-Escalation Phase, patients must be diagnosed with the following:
- 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.
- Relapsed or refractory CMML and has failed treatment with available therapies known to be active for CMML
- Part 2 Expansion Phase:
- Relapsed or refractory LILRB4high AML with myelomonocytic or monoblastic/monocytic differentiation and has failed treatment with available therapies known to be active for AML.
- Hypomethylating-agent naive CMML regardless of LILRB4 expression levels.
- Newly diagnosed high LILRB4 expression monocytic AML patients considered to be ineligible for standard induction therapy.
- Patients must be amenable to serial BM aspirates/biopsies and peripheral blood sampling during the study.
- Patients must be able to understand and willing to sign an informed consent. A legally authorized representative may consent.
- Patients must have an ECOG performance status of 0 to 2
- Patients must have adequate hepatic function
- Patients must have adequate renal function
- Patients must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer.
- Patients must be off systemic calcineurin inhibitors for at least 4 weeks prior to study drug treatment.
- +1 more criteria
You may not qualify if:
- Patients who have previously received a monoclonal antibody therapy targeting LILRB4.
- Patients who have undergone HSCT within 60 days of the first dose of IO-202.
- 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.
- Patients who received an investigational agent \<7 days prior to their first day of study drug administration.
- Patients for whom potentially curative anti-cancer therapy is available.
- Patients who are pregnant or breastfeeding.
- Patients with uncontrolled, active infection.
- Patients with known hypersensitivity to any of the components of the IO-202 formulation.
- Patients with known pulmonary lesions and/or history of pneumonitis or interstitial lung disease.
- Active known malignancy.
- Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) or left ventricular ejection fraction (LVEF) \<40%.
- Ongoing cardiac dysrhythmias Grade 2 or higher per of NCI CTCAE, Version 5.0, Grade ≥2.
- Known or suspected hypersensitivity to recombinant proteins.
- Known active bacterial, viral, and/or fungal infection.
- Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
University California, Davis (117)
Davis, California, 95817, United States
City of Hope (106)
Duarte, California, 91010, United States
University of California, Irvine (107)
Irvine, California, 92868, United States
UCLA, Medical Center Division of Hematology/Oncology (119)
Los Angeles, California, 90095, United States
Stanford University (114)
Palo Alto, California, 94305, United States
University of California, San Francisco (118)
San Francisco, California, 94143, United States
University of Colorado, Anschutz Medical Campus (103)
Aurora, Colorado, 80045, United States
Winship Cancer Institute of Emory University (105)
Atlanta, Georgia, 30322, United States
The University of Chicago (113)
Chicago, Illinois, 60637, United States
Weill Cornell Medical College, New York Presbyterian Hospital (110)
New York, New York, 10021, United States
Cleveland Clinic, Taussig Cancer Institute (111)
Cleveland, Ohio, 44195, United States
Oregon Health and Science University, Center for Hematologic Malignancies (116)
Portland, Oregon, 97239, United States
University of Texas Southwestern, Simmons Comprehensive Cancer Center (104)
Dallas, Texas, 75390, United States
MD Anderson Cancer Center (101)
Houston, Texas, 77030, United States
Related Publications (1)
Aribi A, Mannis GN, Madanat YF, Jonas BA, Dunavin N, Roboz GJ, Jeyakumar D, Garcia-Manero G, Liu H, Carraway HE, Saultz JN, Blum W, Schiller G, Huang T, Woodard P, Klencke B, Liao XC, Xiang H, Pollyea DA, DiNardo CD. A phase 1 study of IO-202, an anti-LILRB4 antibody, in chronic myelomonocytic leukemia and acute myeloid leukemia. Blood Neoplasia. 2025 Jun 9;2(4):100126. doi: 10.1016/j.bneo.2025.100126. eCollection 2025 Nov.
PMID: 40919482DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Hong Xiang, PhD
Immune-Onc Therapeutics
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 20, 2020
First Posted
May 4, 2020
Study Start
September 14, 2020
Primary Completion
January 31, 2025
Study Completion
January 31, 2025
Last Updated
February 14, 2025
Record last verified: 2025-02
Data Sharing
- IPD Sharing
- Will not share