IO-202 Receives FDA Orphan Drug Designation in CMML


An orphan drug designation has been granted by the FDA for IO-202 as a treatment option for patients with chronic myelomonocytic leukemia.

  • IO-202 was granted an FDA orphan drug designation for treating chronic myelomonocytic leukemia (CMML), addressing an unmet need.

  • The agent is a first-in-class, humanized IgG1 antibody that binds to leukocyte immunoglobulin-like receptor subfamily B4 (LILRB4), showing promise in relapsed/refractory CMML and acute myeloid leukemia (AML).

  • IO-202 demonstrated safety and efficacy, with notable responses including complete remission (CR) in AML and clinical benefits in CMML, supporting advancement to dose-expansion phase.

IO-202 has been granted an orphan drug designation from the FDA for the treatment of patients with CMML, according to Immune-Onc Therapeutics, Inc.1

“Although current therapeutic options for CMML can improve a patient’s quality of life, there is a high unmet need for effective disease-modifying approaches that are potentially curative,” said Charlene Liao PhD, chief executive officer and board chair of Immune-Onc, the manufacturer of IO-202, in a press release. “We are very proud that the FDA has granted IO-202 orphan drug designation for the treatment of [patients with] CMML. We look forward to continued collaborations with our investigators and the FDA as we work to bring this potentially important therapy to patients with hard-to-treat blood cancers.”

IO-202 is a first-in-class, humanized IgG1 antibody. The agent has high-affinity binding to LILRB4 and in 2023, received an FDA fast track designation for the treatment of patients with relapsed/refractory CMML. The FDA also granted the agent a fast track designation in February 2022 in relapsed/refractory AML, and an orphan drug designation for the same indication in 2020.

A multicenter, open-label phase 1 study (NCT04372433) is currently ongoing to evaluate IO-202 alone and combined with azacitidine (Vidaza) with or without venetoclax (Venclexta) for the treatment of patients with relapsed/refractory AML with monocytic differentiation or CMML.

Leukemia Image

Leukemia Image

Enrollment in the study is open to patients aged 18 years and older with adequate hepatic and renal function, an ECOG performance status of 2 or lower, and those who have not received systemic calcineurin inhibitors for at least 4 weeks prior to study treatment.2 Once enrolled, patients in the dose-escalation portion are being treated with IO-202 via intravenous infusion given at dose levels ranging from 0.03 mg/kg to 60 mg/kg on days 1 and 15 of each 28-day cycle.3 In addition, patients were given azacitidine at 75 mg/m2 on days 1 through 7 of each cycle.

Investigators are assessing the primary end points of safety and tolerability and the secondary end points of pharmacokinetics, response rates, and incidence of antidrug antibodies against IO-202.2

At the 2023 European Hematology Association congress, results from the dose-escalation portion of the study were presented, highlighting data on 26 patients with AML who received IO-202 alone and 10 patients given IO-202 plus azacitidine. Data from a cohort of patients with CMML who were treated with IO-202 monotherapy (n = 5) and IO-202 plus azacitidine (n = 5) also were presented.3

Finding showed that among patients included in the AML cohort of the phase 1 study, there was 1 patient in the IO-202 monotherapy arm treated at a dose of 9 mg/kg who reached a partial remission (PR). One patient who had high LILRB4 expression and was given IO-202 at 30 mg/kg plus azacitidine achieved a complete remission (CR) lasting longer than 10 months.

One patient in the CMML cohort who received IO-202 alone at a dose increasing from 0.1 mg/kg to 0.3 mg/kg had a clinical benefit which lasted longer than 1 year. Also in this arm, 1 patient had a PR at the 4.5 mg/kg dose, 1 patient had clinical benefit at the 9 mg/kg dose, and 1 patient experienced an optimal marrow response with a duration of over 3 months when treated at the 60 mg/kg dose.

Regarding safety, in the monotherapy arm of the study (n = 31), treatment-related adverse events included vomiting (n = 4), nausea (n = 3), and abdominal pain, chills, fatigue, infusion-related reactions, and headache in 2 patients each. However, no adverse events were reported among those given the combination therapy (n = 15). There were also no deaths associated with IO-202 administration, and no dose-limiting toxicities were observed with the maximum tolerated dose not reached.

Overall, study authors determined that IO-202, administered at a maximum dose of 60 mg/kg twice weekly, was safe and well-tolerated both as monotherapy and in combination with azacitidine, eliciting promising responses. Notably, a CR in a patient with AML and an optimal marrow response in a patient with CMML justified advancing IO-202 to the dose-expansion phase, focusing on AML patients with high LILRB4 expression levels.

  1. Immune-Onc Therapeutics announces orphan drug designation granted by US FDA for IO-202 (anti-LILRB4) for the treatment of chronic myelomonocytic leukemia (CMML). News release. Immune-Onc Therapeutics, Inc. February 21, 2024. Accessed February 23, 2024.
  2. IO-202 as monotherapy and IO-202 plus azacitidine ± venetoclax in patients in AML and CMML. Updated January 8, 2024. Accessed February 23, 2024.
  3. DiNardo C, Pollyea D, Aribi A, et al. A first-in-human phase 1 study of IO-202 (anti-LILRB4 mAb) in acute myeloid leukemia with monocytic differentiation and chronic myelomonocytic leukemia. Presented at: 2023 European Hematology Association Congress; June 8-11, 2023; Frankfurt, Germany. Abstract P536.
Related Videos
Gary J. Schiller, MD, an expert on MDS
Gary J. Schiller, MD, an expert on MDS
Gary J. Schiller, MD, an expert on MDS
Gary J. Schiller, MD, an expert on MDS
Gary J. Schiller, MD, an expert on MDS
Gary J. Schiller, MD, an expert on MDS
A panel of 3 experts on GVHD
A panel of 3 experts on GVHD
Related Content