IO-202 + Azacitidine/Venetoclax for AML and CMML

No longer recruiting at 25 trial locations

Overseen By Yasuhiro Tabata, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Immune-Onc Therapeutics Inc

Must not be taking: Monoclonal antibodies, Corticosteroids

Disqualifiers: Pregnancy, Active infection, CHF, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the safest dose of a new treatment, IO-202, for people with specific types of blood cancer: acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). Researchers are testing IO-202 both alone and in combination with other drugs like Azacitidine (a chemotherapy drug) and Venetoclax (a targeted therapy). The trial seeks participants with AML or CMML who have tried other treatments without success and are experiencing frequent symptoms or complications from their condition. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking systemic calcineurin inhibitors at least 4 weeks before starting the study drug. Additionally, you must not have received systemic anti-cancer therapy or radiotherapy within 7 days before the first dose, except for hydroxyurea or leukapheresis, which are allowed up to 24 hours prior.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that IO-202, an experimental treatment, is generally safe for people. Studies have found that patients with certain blood cancers, such as AML and CMML, tolerate it well both alone and with azacitidine. In these studies, doses of IO-202 reached up to 60 mg/kg twice a week without causing serious side effects.

When considering the combination of IO-202 with azacitidine and venetoclax, it is important to note that azacitidine and venetoclax are already approved for treating certain blood cancers, indicating their well-established safety. Previous studies of this combination have shown that patients usually tolerate it well.

Overall, existing research suggests that the treatments tested in this trial have been safe for previous patients. However, since this trial is still in the early stages, the main goal remains to assess safety and how well patients can handle the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for AML and CMML because they target the LILRB4 protein, which may play a role in cancer cell survival. IO-202 is unique because it is designed to block this protein, potentially reducing cancer cell resistance to treatment. The combination with Azacitidine and Venetoclax could enhance treatment effectiveness, especially for patients who are unfit for more intensive therapies. Unlike traditional chemotherapy, which can be harsh, these treatments aim to be more targeted, offering hope for better outcomes with potentially fewer side effects.

What evidence suggests that this trial's treatments could be effective for AML and CMML?

Research has shown that combining IO-202 and azacitidine may effectively treat certain blood cancers, such as AML and CMML, particularly in patients unresponsive to other treatments. In this trial, some participants will receive IO-202 and azacitidine, while others will receive IO-202 alone. Additionally, one treatment arm includes IO-202, azacitidine, and venetoclax. IO-202 is a medicine that helps the immune system better identify and attack cancer cells. When combined with azacitidine and venetoclax, this treatment could be a strong option for AML patients who cannot undergo intensive chemotherapy. Early results are promising, but further research is needed to confirm these findings. ^{1 2 3 6 7}

Who Is on the Research Team?

Hong Xiang, PhD

Principal Investigator

Immune-Onc Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults (18+) with certain types of blood cancer: relapsed or refractory Acute Myeloid Leukemia (AML) with specific differentiation, or Chronic Myelomonocytic Leukemia (CMML). Participants must have failed previous treatments and be in good enough health to give consent and undergo regular bone marrow/blood tests. Pregnant women, those with other severe illnesses, recent transplants, or known allergies to similar drugs cannot join.

Inclusion Criteria

I have CMML and have never been treated with hypomethylating agents.

I have AML that didn't respond to treatment and fits specific types.

I have CMML that didn't respond to treatment or has come back.

Exclusion Criteria

I currently have an active infection.

Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol

Patients who are pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive IO-202 monotherapy or IO-202 plus Azacitidine in ascending doses to assess safety and tolerability

28-day cycles

Multiple visits per cycle

Dose Expansion

Participants receive IO-202 plus Azacitidine ± Venetoclax to further evaluate safety and clinical activity

28-day cycles

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• IO-202
• Venetoclax

Trial Overview The study is testing IO-202 alone and combined with Azacitidine ± Venetoclax in patients with AML and CMML. It aims to find the safest high dose (MTD/MAD) for future studies by gradually increasing amounts in different groups of participants until they reach a level that's effective but tolerable.

How Is the Trial Designed?

Group I: Dose Expansion of IO-202 plus Azacitidine CMML Experimental Treatment 1 Intervention

To enroll hypomethylating-agent naive CMML patients.

Group II: Dose Expansion of IO-202 plus Azacitidine AML Experimental Treatment 1 Intervention

To enroll high LILRB4 expression monocytic AML patients refractory to or relapsed after available therapies known to be active in AML.

Group III: Dose Expansion of IO-202 plus Azacitidine + Venetoclax (Ven) Experimental Treatment 1 Intervention

To enroll newly diagnosed high LILRB4 expression AML patients who are unfit for intensive induction chemotherapy.

Group IV: Dose Escalation of IO-202 Plus Azacitidine Experimental Treatment 1 Intervention

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.

Group V: Dose Escalation of IO-202 Experimental Treatment 1 Intervention

Dose cohorts treated with intravenous (IV) IO-202 monotherapy in ascending doses.

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Immune-Onc Therapeutics Inc

Lead Sponsor

Trials

3

Recruited

180+

Immune-Onc Therapeutics

Lead Sponsor

Trials

5

Recruited

740+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Citations

1. targetedonc.com targetedonc.com/view/io-202-monotherapy-and-combination-demonstrates-efficacy-in-aml-and-cmml

IO-202 Monotherapy and Combination Demonstrates ... A phase 1 trial shows IO-202 combined with azacitidine effectively treats relapsed/refractory monocytic leukemias, demonstrating promising ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04372433

Study Details | NCT04372433 | IO-202 as Monotherapy ... To assess safety and tolerability at increasing dose levels of IO-202 in successive cohorts of participants with AML with monocytic differentiation and CMML ...

3. ashpublications.org ashpublications.org/bloodneoplasia/article/doi/10.1016/j.bneo.2025.100126/537697/A-Phase-1-Study-of-IO-202-an-Anti-LILRB4-Antibody

A phase 1 study of IO-202, an anti-LILRB4 antibody, in chronic ... Herein, we present the phase 1a dose escalation data of IO-202 as monotherapy and in combination with azacitidine (AZA) in patients with relapsed/refractory (R/ ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2950328025000615

A phase 1 study of IO-202, an anti-LILRB4 antibody, in ... Herein, we present the phase 1a dose escalation data of IO-202 as monotherapy and in combination with azacitidine (AZA) in patients with relapsed/refractory (R/ ...

5. onclive.com onclive.com/view/io-202-plus-azacitidine-could-bring-long-awaited-change-in-hma-naive-cmml

IO-202 Plus Azacitidine Could Bring Long-Awaited ... Gabriel Mannis, MD, discusses the observed clinical activity and manageable safety profile of IO-202 combined with azacitidine in CMML.

6. targetedonc.com targetedonc.com/view/first-in-class-antibody-io-202-demonstrates-tolerability-and-response-in-cmml

First-in-Class Antibody IO-202 Demonstrates Tolerability ... The IOS-202/azacitidine combination revealed a complete response of 27.8% and an overall response rate of 66.7% in patients with chronic ...

7. journals.lww.com journals.lww.com/hemasphere/fulltext/2023/08003/p536__a_first_in_human_phase_1_study_of_io_202.437.aspx

p536: a first-in-human phase 1 study of io-202 (anti-lilrb4 ... Aims: The presentation will report clinical trial data of IO-202 from the dose escalation (Part 1) stage of the first-in-human phase 1 study in AML and CMML ...