FDA Grants Fast Track Status to IO-202 for Relapsed/Refractory AML

The FDA has granted a fast track designation to IO-202, a first-in-class anti-LILRB4 myeloid checkpoint inhibitor, as a potential therapeutic option for patients with relapsed or refractory acute myeloid leukemia.

The FDA has granted a fast track designation to IO-202, a first-in-class anti-LILRB4 myeloid checkpoint inhibitor, as a potential therapeutic option for patients with relapsed or refractory acute myeloid leukemia (AML).1

Preclinical studies evaluating the immunotherapy showed that in hematologic malignancies, the agent converts “don’t-kill-me” signals to “kill-me” signals through the activation of T-cell killing. Moreover, by inhibiting the infiltration of blood cancer cells, the agent is also able to convert “don’t-find-me” signals to “find me” signals. In a solid tumor model in vivo, the checkpoint inhibitor was found to boost the functionality of dendritic cells and activate T cells in vitro, resulting in the inhibition of tumor growth.

With this designation, IO-202 may be eligible for more frequent interactions and written communications with the regulatory agency to discuss the development plan and data collection to support a pathway for potential approval. The fast track designation also makes the agent eligible for accelerated approval and priority review if select criteria are met.

“We are pleased that the FDA has granted IO-202 fast track designation in recognition of its potential to improve outcomes for people with relapsed or refractory AML,” Paul Woodward, PhD, chief medical officer of Immune-Onc Therapeutics, Inc., stated in a press release. “We look forward to working closely with the FDA to accelerate the clinical development of IO-202, which is currently being evaluated as a monotherapy and in combination with other agents in a phase 1 dose escalation and expansion trial in patients with AML with monocytic differentiation and in chronic myelomonocytic leukemia [CMML].”

The first portion of the phase 1 trial (NCT04372433) is enrolling those who are at least 18 years of age who have relapsed or refractory AML or CMML in whom treatment with available therapies have failed.2 The second portion will enroll those with relapsed or refractory AML with myelomonocytic or monoblastic/monocytic differentiation that has failed available treatment, an ECOG performance status of 0 to 2, and acceptable hepatic and renal function.

Those who previously received IO-202, who have undergone hematopoietic stem cell transplantation within 60 days of the first dose of the agent, those who received systemic anticancer therapy or radiotherapy less than 7 days before first administration of the agent, those who received an investigational drug less than 1 week before the first day of the drug, and those with uncontrolled, active infection, will be excluded.

The primary outcome measures of the trial include the incidence and severity of toxicities, as well as the tolerability of the agent, as measured by the incidence and duration of dose interruptions and reductions. Secondary outcome measures include pharmacokinetics, incidence of antidrug antibodies against IO-202, and response rates.

Other outcome measures of interest include correlating target expression with response rates, correlating target expression with rates of toxicities, and to examine immunophenotype of leukemic blasts from bone marrow aspirates following study treatment.

Previously, in November 2020, the FDA granted an orphan drug designation to IO-202 for the treatment of patients with AML.3


  1. Immune-Onc Therapeutics receives FDA fast track designation for IO-202, the first anti-LILRB4 myeloid checkpoint inhibitor, for the treatment of relapsed or refractory acute myeloid leukemia (AML). News release. Immune-Onc Therapeutics, Inc; February 17, 2022. Accessed February 17, 2022. https://yhoo.it/3GXW3nS
  2. IO-202 as monotherapy in patients in AML and CMML. ClinicalTrials.gov. Updated September 16, 2021. Accessed February 17, 2022. https://clinicaltrials.gov/ct2/show/NCT04372433
  3. Immune-Onc Therapeutics announces orphan drug designation of IO-202 (anti-LILRB4) for treatment of AML and poster presentation at ASH 2020. News release. Immune-Onc Therapeutics, Inc.; November 10, 2020. Accessed February 17, 2022. https://bit.ly/3oVBhiJ