FDA Grants Fast Track Designation to ICT01 in Combination With Azacitidine and Venetoclax for Acute Myeloid Leukemia

ICT01 (ImCheck) in combination with azacitidine (Vidaza; Bristol-Myers) and venetoclax (Venclexta; AbbVie Inc) has been granted a fast track designation for the treatment of patients with acute myeloid leukemia (AML) 75 years or older who have comorbidities that prevent use of standard intensive induction chemotherapy. The decision is based on promising results from the phase 1 dose-escalation portion of the EVICTION study (NCT04243499) evaluating ICT01 as a monotherapy in relapsed/refractory hematological malignancies.¹

ICT01 treatment safely induced the activation and migration of γ9δ2 T cells from the blood within hours of dosing. Image Credit: © Anastasiia - stock.adobe.com

AML is an aggressive type of hematological cancer characterized by the overproduction of abnormal blood cells in the bone marrow, resulting in symptoms such as fatigue, fever, infection, or increased bleeding. Risk factors for AML are diverse, ranging from modifiable actions such as smoking cessation, to unchangeable factors like genetics. AML can also develop as a secondary cancer after radiation exposure and prior treatment with certain chemotherapy drugs. These treatments can damage the DNA of cells, leading to mutations that increase AML risk.^2,3

ICT01 is a humanized anti-butyrophilin 3A (anti-BTN3A) monoclonal antibody that selectively activates γ9δ2 T-cells, innate mechanisms in the immune system responsible for immunosurveillance of malignancy and infections. The 3 isoforms of BTN3A are overexpressed in a number of malignancies including solid tumors, such as bladder, melanoma, and colorectal, as well as in multiple hematological malignancies. The safety and efficacy of ICT01 as a monotherapy and treatment for AML was evaluated in the international, multicenter, open label, multicohort phase 1/2a EVICTION trial. Part 1 of the trial assess the preliminary safety, efficacy, and tolerability of ICT01 as a monotherapy for solid tumors and hematologic malignancies, and as a combination therapy with pembrolizumab for solid tumors. Part 2 is a cohort expansion based on results from the first part of the study.^4-6

The primary end points of the study consisted of treatment-adverse events (AE) and the disease control rate (DCR) defined as the sum of complete response (CR), CR with incomplete recovery (CRi), partial response (PR) and stable disease (SD). Secondary end points were circulating γ9δ2 T cell measurements as well as pharmacokinetic and pharmacodynamic analyses.⁶

The hematologic malignancy group included 26 patients who failed all available treatment options with either AML (n=24), diffuse large B-cell lymphoma (n=1), and follicular lymphoma (n=1) who were assigned to receive ICT01 as a monotherapy. ICT01 was administered at doses ranging from 200 μg to 75 mg every 21 days. According to the data, ICT01 treatment safely induced the activation and migration of γ9δ2 T cells from the blood within hours of dosing.⁶

“The growing body of data on ICT01 together with the FDA’s fast track designation further validates our development of ICT01 in first-line AML patients 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 press release. “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.”⁵

REFERENCES

1. First-in-human study of ict01 in patients with advanced cancer (eviction). ClinicalTrials.gov Identifier: NCT04243499. Updated July 22, 2024. Accessed September 18, 2024. https://www.clinicaltrials.gov/study/NCT04243499

2. Acute myeloid leukemia treatment (pdq®)–patient version. National Cancer Institute. August 26, 2024. Accessed September 18, 2024. https://www.cancer.gov/types/leukemia/patient/adult-aml-treatment-pdq#:~:text=and%20treatment%20options.-,Adult%20acute%20myeloid%20leukemia%20(AML)%20is%20a%20type%20of%20cancer,if%20it%20is%20not%20treated.

3. Risk factors for acute myeloid leukemia (aml). American Cancer Society. February 27, 2024. Accessed September 18, 2024. https://www.cancer.org/cancer/types/acute-myeloid-leukemia/causes-risks-prevention/risk-factors.html#:~:text=Patients%20with%20cancer%20who%20are,myelodysplastic%20syndrome%20before%20the%20AML

4. About ICT01. ImCheck Therapuetics. Accessed September 18, 2024. https://www.imchecktherapeutics.com/pipeline/ict01/

5. 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. 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/

6. Imcheck to present new positive data on ict01 monotherapy in hematological cancers at esmo 2023. ImCheck Therapuetics. October 16, 2023. Accessed September 18, 2024. https://www.imchecktherapeutics.com/all-press-release/news/imcheck-to-present-new-positive-data-on-ict01-monotherapy-in-hematological-cancers-at-esmo-2023/