FDA Grants Orphan Drug Designation to ICT01 for Acute Myeloid Leukemia

The FDA has granted orphan drug designation to ICT01, a humanized anti-butyrophilin 3A monoclonal antibody designed to selectively activate γ9δ2 T cells, for the treatment of patients with acute myeloid leukemia (AML).¹ This is the agent’s second designation, following its earlier fast track designation in combination with azacitidine and venetoclax (Venclexta) as frontline treatment for patients 75 years of age or older with AML who are unfit for induction chemotherapy.²

“Receiving FDA orphan drug designation for ICT01 is a significant recognition of ICT01’s innovative therapeutic potential to meet the urgent unmet medical needs of AML patients," Stephan Braun, MD, PhD, chief medical officer of ImCheck Therapeutics, stated in a news release.¹ “This important regulatory milestone reinforces our confidence that ICT01 will become the first immunotherapy for [patients with AML] and supports our goal of rapidly advancing ICT01 into pivotal studies based on the unprecedented results observed in the clinic to date.”

The agent is currently under evaluation in the first-in-human phase 1/2 EVICTION study (NCT04243499) in patients with advanced cancer.³

“Orphan drug designation is a catalyst,” Pierre d’Epenoux, chief executive officer of ImCheck Therapeutics, added in the news release.¹ “It validates our regulatory strategy, de-risks and supports clinical development acceleration, and sends a strong signal about the unique potential of ICT01 to transform AML treatment as well as other solid tumor indications.”

Findings from the dose optimization portion of EVICTION were presented at the 2025 ASCO Annual Meeting.⁴ This portion of the study enrolled patients with newly diagnosed AML who were ineligible for intensive chemotherapy/hematopoietic stem cell transplant (HSCT). Patients were excluded if they were eligible for intensive chemotherapy/HSCT; harbored translocations in 15;17, 8;21, or 16;16, or inversions in chromosome 16; had received a prior diagnosis of myeloproliferative neoplasm, polycythemia vera, chronic myeloid leukemia, or AML with BCR-ABL1 translocation; received prior venetoclax; had exposure to systemic corticosteroids in the past 28 days; or had active autoimmune disease.

Following screening and enrollment patients were randomly assigned to 75 mg of ICT01 (ICT01^high) in combination with venetoclax and azacitidine every 4 weeks (n = 16) or 10 mg of ICT01 (ICT01^low) in combination with venetoclax and azacitidine every 4 weeks (n = 29), with a plan to enroll up to 40 patients in this cohort. The ICT01^high arm was discontinued in 2024 following a recommendation from the safety review committee.

The primary end point was complete response (CR) rate per European LeukemiaNet 2022 criteria. Secondary end points included composite CR rate (CRc), overall survival (OS), event-free survival, safety, pharmacokinetics, and pharmacodynamics.

At the time of the presentation 45 patients had received at least 1 dose of study therapy and were evaluable for safety and 39 were evaluable for efficacy.

The overall CR rate in the ICT01^low population was 74%; the CRc rate was 96%. The CR rates in cycles 1, 2, 3, and 4 were 39%, 57%, 70%, and 74%, respectively. The respective CRc rates were 57%, 87%, 96%, and 96%. Notably, 7 of 9 patients evaluable for minimal residual disease (MRD) achieved MRD negativity.

Responses in the ICT01^low cohort were also evaluated according to molecular subtypes. Within the adverse-, intermediate-, and favorable-risk subgroups, the CR/CRc rates were 60%/83%, 67%/100%, and 82%/100%, respectively.

At a median follow-up of 7.5 months (95% CI, 6.2-11.4), patients had received a median of 4 cycles of therapy. The median duration of CRc was 11.5 months (95% CI, 6.6-not evaluable).

Additional efficacy results indicated that the median OS was not reached in the ICT01^low population. The 9-month OS rate was 83%.

With respect to safety, the following treatment-emergent adverse effects were recorded within the ICT01^low cohort: decreased neutrophil count (any grade, 93%; grade ≥3, 90%), decreased platelet count (any grade, 83%; grade ≥3, 66%), decreased lymphocyte count (any grade, 90%; grade ≥3, 62%), decreased hemoglobin (any grade, 69%; grade ≥3, 41%), febrile neutropenia (any grade, 45%; grade ≥3, 45%), constipation (any grade, 41%; grade ≥3, 3%), diarrhea (any grade, 45%; grade ≥3, 0%), nausea (any grade, 38%; grade ≥3, 0%), vomiting (any grade, 24%; grade ≥3, 0%), asthenia/fatigue (any grade, 31%; grade ≥3, 3%), sepsis/bacteremia (any grade, 28%; grade ≥3, 28%), pneumonia (any grade, 14%; grade ≥3, 14%), increased bilirubin (any grade, 45%; grade ≥3, 0%), and alkaline phosphatase increase (any grade, 34%; grade ≥3, 0%).

References

1. ImCheck’s ICT01 receives FDA orphan drug designation for treatment of acute myeloid leukemia. News release. ImCheck Therapeutics. July 18, 2025. Accessed July 18, 2025. https://www.imchecktherapeutics.com/all-press-release/news/imchecks-ict01-receives-fda-orphan-drug-designation-for-treatment-of-acute-myeloid-leukemia/
2. 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 July 18, 2025. 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/
3. First-in-human study of ICT01 in patients with advanced cancer (EVICTION). ClinicalTrials.gov. Updated May 31, 2025. Accessed July 18, 2025. https://www.clinicaltrials.gov/study/NCT04243499
4. Dumas PY, Maiti A, Peterlin P, et al. γ9δ2 T-cell activation (γδTCA) with ICT01 combined with azacitidine-venetoclax (AV) for older/unfit adults with newly diagnosed (ND) AML: preliminary efficacy and dose selection in phase 1/2 study EVICTION. J Clin Oncol. 2025;43(suppl 16):6507. doi:10.1200/JCO.2025.43.16_suppl.6507