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

CMML Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04372433
• Other study ID #: IO-202-CL-001
• Status: Recruiting
• Phase: Phase 1
• Start date: September 14, 2020
• Est. completion date: January 31, 2027

Study information

• Verified date: March 2024
• Source: Immune-Onc Therapeutics
• Contact: Yasuhiro Tabata, MD, PhD
• Phone: 650-457-1741
• Email: yasuhiro.tabata[@]immuneonc.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: January 31, 2027
• Est. primary completion date: January 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• CMML

Intervention

Biological:
• IO-202
IO-202 as monotherapy
• IO-202 and Azacitidine
IO-202 and azacitidine combination therapy
• IO-202 and Azacitidine + Venetoclax
IO-202 and azacitidine + venetoclax combination therapy
• IO-202 and Azacitidine
IO-202 and azacitidine combination therapy

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Immune-Onc Therapeutics	California Institute for Regenerative Medicine (CIRM)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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