FDA Grants Fast Track Designation to ICT01 Plus Azacitidine/Venetoclax in Treatment-Naive AML

The FDA has granted fast track designation to ICT01 in combination with azacitidine (Vidaza) and venetoclax (Venclexta) for the frontline treatment of patients 75 years of age or older with acute myeloid leukemia (AML) who are unfit for induction chemotherapy.¹

Findings from the dose-escalation portion of the phase 1/2a EVICTION study (NCT04243499) presented during the 2023 ESMO Congress showed that patients with relapsed/refractory hematologic malignancies whose disease progressed following all available treatment options (n = 26), which included patients with AML (n = 24), diffuse large B-cell lymphoma (DLBCL; n = 1), and follicular lymphoma (n = 1), did not experience any dose-limiting toxicities (DLTs) at doses of ICT01 ranging from 200 μg to 75 mg every 21 days.²

Additionally, the disease control rate (DCR) at 8 weeks or beyond (n = 10) was 30%, including 1 patient with DLBCL who achieved a partial response at the 7-mg ICT01 dose level from week 4 to 94. In the 20-mg dose group, 2 patients with AML achieved stable disease at week 8. Based on these results, the randomized dose-optimization cohort of EVICTION was initiated in October 2023 to evaluate 2 doses of ICT01 in combination with azacitidine and venetoclax.^1,2

“The growing body of data on ICT01 together with the FDA’s fast track designation further validates our development of ICT01 in [patients with] first-line AML and highlights the critical need for therapies that generate higher response rates and improve overall survival for these patients,” Stephan Braun, MD, PhD, chief medical officer of ImCheck Therapeutics, said in a news release.¹ “We are highly encouraged by ICT01’s potentially broad applicability in solid tumor and hematological cancer indications and look forward to sharing updates from the EVICTION study at upcoming scientific conferences.”

ICT01 is a humanized anti-butyrophilin 3A monoclonal antibody that selectively activates γ9δ2 T cells. The open-label EVICTION trial is a first-in-human study of ICT01 in patients with advanced solid or hematologic malignancies. To be eligible for the trial, patients needed to have an ECOG performance status of 1 or less, a life expectancy of over 3 months, and at least 1 measurable lesion per RECIST 1.1 criteria.^1,3

The primary end point in parts 1 and 2 is the incidence of treatment-emergent adverse effects (TRAEs); the coprimary end points in part 2 is DCR per RECIST 1.1 criteria for patients with solid tumors and DCR per RECIL or International Working Group criteria for patients with lymphoma. Secondary end points included objective response rate per RECIST 1.1 criteria for patients with solid tumors, change from baseline in the number of circulating gamma delta T cells, change from baseline in the activation state of circulating gamma delta T cells, and pharmacokinetics.³

Additional safety findings from EVICTION presented during the 2023 ESMO Congress showed that the most common TRAEs were grade 1/2 first-dose infusion-related reactions, nausea, fever, and vomiting. Two instances of grade 3 or higher neutropenia were reported and were able to be resolved with treatment.²

The dose-optimizing and efficacy-estimating portion of EVICTION has enrolled 29 patients to date. Pharmacodynamic and pharmacokinetic results have demonstrated reproducible activation and migration of γ9δ2 T cells from the blood within hours of dosing ICT01 in combination with azacitidine and venetoclax, indicating effective target engagement.¹

References

1. ImCheck receives FDA fast track designation for ICT01 in combination with azacitidine and venetoclax in first-line acute myeloid leukemia for patients unfit for induction chemotherapy treatment. News release. ImCheck Therapeutics. September 18, 2024. Accessed September 18, 2024. https://www.imchecktherapeutics.com/all-press-release/news/imcheck-receives-fda-fast-track-designation-for-ict01-in-combination-with-azacitidine-and-venetoclax-in-first-line-acute-myeloid-leukemia-for-patients-unfit-for-induction-chemotherapy-treatment/
2. Garciaz S, Champiate S, Peterlin P, et al. Activation of γ9δ2 T cells by ICT01 as a novel immunotherapeutic approach for relapsed/refractory hematologic cancers (EVICTION trial). Ann Oncol. 2023;34(suppl 2):S543-S553. doi:10.1016/S0923-7534(23)01263-2
3. First-in-human study of ICT01 in patients with advanced cancer (EVICTION). ClinicalTrials.gov. Updated July 22, 2024. Accessed September 18, 2024. https://www.clinicaltrials.gov/study/NCT04243499