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

An FDA fast track designation has been granted to IO-202 for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML), according to an announcement by Immun-Onc Therapeutics, Inc.¹

IO-202 is a first-in-class myeloid checkpoint inhibitor targeting leukocyte immunoglobulin-like receptor B4 agent. ITL3 drugs can inhibit antigen presenting cell activation leading to immune tolerance. ITL3 tends to be expressed on hematologic cancer cells and monocytic myeloid cells in the solid tumor environment.

In a preclinical in vitro model, treatment with the ITL3 inhibitor in mice led to promoted DC maturation, activation, and an antigen presenting phenotype along with a boost in the ability to activate allogeneic T cells. Moreover, anti-tumor immunity was observed with the ITL3 inhibitor in an in vivo solid tumor model.²

“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,” said Paul Woodard, PhD, chief medical officer of Immune-Onc, 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).”

Treatment with IO-202 is under investigation in a phase 1, multicenter, open-label, dose-escalation and expansion study. The study will enroll 44 patients with either AML or CMML to receive IO-202 in ascending doses every 2 weeks in the dose-escalation phase followed by IO-202 at the recommended phase 2 dose and frequency in the dose expansion phase.³

As coprimary end points, the study is evaluating safety and tolerability measured by the incidence of adverse events (AEs), severity of AEs, and the incidence of dose interruptions and dose reductions. The secondary end points of the study include pharmacokinetics, the incidence of anti-drug antibodies against IO-202, and the rate of response to the agent in patients with anti-drug antibodies.

As exploratory outcomes, the study is also looking into target expression with response rates, target expression with rates of AEs, and immunophenotype of leukemic blasts after study treatment.

To be included in the study, patients must be 18 years of age or older with relapsed or refractory AML or CMML that has failed treatment with available therapies known to be active in their disease. Patients are also required to have an ECOG performance status of 0 to 2, adequate hepatic function, adequate renal function, and be recovered from any toxicities from prior treatment. Those who were receiving calcineurin inhibitors must be off the treatment for at least 4 weeks prior to the study treatment dosing. All premenopausal female patients must produce a negative pregnancy test within 7 days prior to treatment in the study.

The study excludes any patient who has been previously treated with IO-202; undergone hematopoietic stem cell transplant within 60 days of the first dose of IO-202 in the study; or received anti-cancer therapy, radiotherapy, or an investigational agent within 7 days prior to study treatment.

Individuals are ineligible to enroll in the study if they have hypersensitivity to IO-202, have active or uncontrolled infection, active known malignancy, and other factors that may interfere with the activity and safety of IO-202.

The fast track designation granted to IO-202 follows an orphan drug designation granted in 2020. With the fast track status, the development and review of any approval application will be expedited by the FDA in an effort to fill unmet medical needs for novel AML therapies.¹

_References:

_{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. February 17, 2022. Accessed February 18, 2022. https://bit.ly/3Bul21c}

_{2. Costa MJ, Huang T, Ma J, et al. 1629 - IO-202, a first-in-class LILRB4 antagonist antibody, activates dendritic cells and inhibits solid tumor growth in preclinical studies. Presented at. 2021 American Association for Cancer Research Annual Meeting; April 10-15, 2021; Virtual. Abstract CT008.}

_{3. IO-202 as monotherapy in patients in aml and CMML. Clinicaltrials.gov. Accessed February 18, 2022. https://bit.ly/3uYBQvX}