The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to ICT01, a novel treatment option for the treatment of acute myeloid leukemia (AML) being developed by ImCheck Therapeutics.
ICT01 is a humanized anti-butyrophilin 3A (BTN3A, also known as CD277) monoclonal antibody designed to selectively activate γ9δ2 T cells, which are responsible for immunosurveillance of malignancy and infections. Gamma delta T (γδ T) cells are among the most potent cytotoxic lymphocytes. [1]
The three isoforms of BTN3A targeted by ICT01 are overexpressed on many solid tumors (e.g., melanoma, urothelial cell, colorectal, ovarian, pancreatic, and lung cancer) and hematologic malignancies (e.g., leukemia and lymphomas) and also expressed on the surface of innate (e.g., γδ T cells and NK cells) and adaptive immune cells (T cells and B cells). BTN3A is essential for the activation of the anti-tumor immune response of γ9δ2 T cells.[1][2]
ICT01 selectively activates circulating γ9δ2 T cells leading to migration of γ9δ2 T cells out of the circulation and into the tumor tissue and triggers a downstream immunological cascade through secretion of pro-inflammatory cytokines, including but not limited to IFNγ and TNFα, further augmenting the anti-tumor immune response. Anti-tumor activity and efficacy of ICT01 have been shown in patients across several cancer indications.[1][2]
The investigational drug has shown unprecedented remission rates in newly diagnosed AML patients, offering new hope for older or unfit individuals who are not eligible for intensive chemotherapy as demonstrated by data presented at past AACR, ASCO, ASH, ESMO and SITC conferences.
A significant clinical challenge
Acute myeloid leukemia (AML) remains a significant clinical challenge, particularly for older or unfit patients who are not eligible for intensive chemotherapy. While the combination of venetoclax and azacitidine has become the standard non-intensive regimen, this approach is not curative and relapse rates remain high.
Most patients are not eligible for stem cell transplantation, often due to age, comorbidities, or insufficient response, and face limited treatment options and poor overall survival. Despite AML’s known sensitivity to immune-mediated control, current immunotherapies targeting PD-1, TIM-3, or CD47 have not delivered meaningful clinical benefit. This underscores the urgent need for novel immuno-oncology approaches. Recently, γ9δ2 T cells, with their cytotoxic activity and unique dual role in both innate and adaptive immunity, have emerged as promising immune modulators. Their association with reduced relapse and prolonged survival, particularly in the post-transplant setting, suggests that enhancing their anti-leukemic potential could offer a meaningful new treatment option for high-risk AML patients.
“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,” said Stephan Braun, MD, PhD, Chief Medical Officer of ImCheck Therapeutics.
“This important regulatory milestone reinforces our confidence that ICT01 will become the first immunotherapy for AML patients and supports our goal of rapidly advancing ICT01 into pivotal studies based on the unprecedented results observed in the clinic to date,” Braun added.
Phase 1 / 2 EVICTION study
In an oral presentation at the 2025 annual meeting of the American Society of Clinical Oncology (ASCO), ImCheck reported results from the Phase 1 / 2 EVICTION study, evaluating ICT01 in combination with azacitidine and venetoclax (Aza-Ven) in newly diagnosed AML patients unfit for intensive chemotherapy.
The study results showed remarkably high remission rates and a positive overall survival signal were observed across a broad range of molecular subtypes, in particular those that are typically less responsive to Aza-Ven. The combination demonstrated a clinically well-manageable safety profile, with Grade ≥3 adverse events consistent with the expected hematological toxicity of Aza-Ven and AML itself.
“Orphan drug designation is a catalyst,” noted Pierre d’Epenoux, Chief Executive Officer of ImCheck Therapeutics
“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,” d’Epenoux explained.
The FDA’s orphan drug designation is granted to drugs and biologics intended for the treatment, diagnosis, or prevention of rare diseases affecting fewer than 200,000 people in the United States. The designation is designed to encourage the development of therapies for underserved patient populations and offers benefits including tax credits for clinical trials, exemption from certain FDA fees, and up to seven years of marketing exclusivity upon approval. Additionally, the designation gives access to regulatory assistance for the drug development process.
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Note: In developing ICT01, ImCheck Therapeutics benefits from the pioneering research of Prof. Daniel Olive (INSERM, CNRS, Institut Paoli Calmettes, Aix-Marseille University), a global leader in γ9δ2 T cells and butyrophilins, as well as the expertise of a seasoned management team and the commitment of leading U.S. and European investors.
Clinical trials
First-in-Human Study of ICT01 in Patients With Advanced Cancer (EVICTION) – ClinicalTrials.gov ID NCT04243499
Phase 1/2a Study of ICT01 Plus Low Dose SC IL-2 in Patients With Advanced Solid Tumors (EVICTION-2) ClinicalTrials.gov ID NCT05307874
Reference
[1] De Gassart A, Le KS, Brune P, Agaugué S, Sims J, Goubard A, Castellano R, Joalland N, Scotet E, Collette Y, Valentin E, Ghigo C, Pasero C, Colazet M, Guillén J, Cano CE, Marabelle A, De Bonno J, Hoet R, Truneh A, Olive D, Frohna P. Development of ICT01, a first-in-class, anti-BTN3A antibody for activating Vγ9Vδ2 T cell-mediated antitumor immune response. Sci Transl Med. 2021 Oct 20;13(616):eabj0835. doi: 10.1126/scitranslmed.abj0835. Epub 2021 Oct 20. PMID: 34669444.
[2] Immunotherapy Activates Antitumor γ9δ2 T Cells. Cancer Discov. 2021 Jun;11(6):OF3. doi: 10.1158/2159-8290.CD-NB2021-0334. Epub 2021 Apr 14. PMID: 33853789.
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