ImCheck Announces First Patients Dosed in Phase 2 of EVICTION Trial for ICT01

ImCheck Therapeutics recently announced the first patients have been dosed in the Phase 2a monotherapy expansion arm in the ongoing Phase 1/2a EVICTION clinical trial of ICT01, a γ9δ2 T cell-activating monoclonal antibody targeting BTN3A. ImCheck will test two dose levels of ICT01 in patients with second- and third-line ovarian cancer or head and neck squamous cell carcinoma in the initial expansion arms.

ImCheck has presented results from Phase 1 of the EVICTION trial in oral presentations at major medical conferences in 2021, including AACR, ESMO and SITC, demonstrating ICT01’s safety, its powerful mechanism of action leading to activation, migration and tumor infiltration of circulating 92 T cells, CD8 T cells & NK cells, and initial tumor responses.

“We continue to meet our clinical development milestones and build on the positive clinical results we have reported to date. This is thanks to the great collaboration between the ImCheck team and an outstanding group of clinicians at trial centers in Europe and in the US,” said Pierre d’Epenoux, Chief Executive Officer of ImCheck Therapeutics. “ImCheck has now transitioned into a mid-stage clinical company which speaks to our commitment to developing new therapeutic options for cancer patients. As the most clinically-advanced company in the field of antibody therapies activating gamma-delta T cells, we aim to set a strong precedent for the development of innovative treatments in this area.”

Additional expansion arms are planned in hematological malignancies and in combination with pembrolizumab in solid tumor indications later this year.

EVICTION is a first-in-human, dose escalation (Part 1) and cohort expansion (Part 2) clinical trial of ICT01 in patients with various advanced relapsed or refractory solid or hematologic cancers that have exhausted standard of care treatment options. Part 1 is a basket trial designed to characterize the preliminary safety, tolerability, and pharmacodynamic activity of ICT01 as monotherapy (Group A: solid tumors; Group B: hematologic tumors) and in combination with pembrolizumab (Group C: solid tumors). Group A included bladder, breast, colorectal, gastric, melanoma, ovarian, prostate, and pancreatic cancer patients, Group B included acute myeloid leukemia, acute lymphocytic leukemia, follicular lymphoma, and diffuse large B cell lymphoma patients, and Group C included bladder, head and neck squamous cell carcinoma, melanoma, and non-small cell lung cancer patients. Basket trials are a clinical trial design that allows new drugs to be tested rapidly in a range of indications, providing initial data on multiple parameters that can contribute to an accelerated development timeline. Part 2 of the trial is a Phase II cohort expansion in selected indications based on Part I of the study with both monotherapy and combination settings. First indications selected for this Phase II part are ovarian cancer and Head and Neck Squamous Cell Carcinoma (HNSCC). More information on the EVICTION trial can be found at clinicaltrials.gov (NCT04243499).

ICT01 is a humanized, anti-BTN3A (also known as CD277) monoclonal antibody that selectively activates γ9δ2 T cells, which are part of the innate immune system that is responsible for immunosurveillance of malignancy and infections. The 3 isoforms of BTN3A targeted by ICT01 are overexpressed on a number of solid tumors (e.g., bladder, colorectal, melanoma, ovarian, pancreatic, lung) and hematologic cancers (eg, leukemia & lymphoma) and also expressed on the surface of innate (eg, 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.

As demonstrated in EVICTION data presented at AACR, ICT01 selectively activates circulating γ9δ2 T cells that leads to migration of γ9δ2 T cells out of the circulation and into target tissue (eg, tumors), while also activating the tumor-resident γ9δ2 T cells to directly kill malignant cells, which is accompanied by secretion of two key inflammatory cytokines, IFNg and TNFa, that contribute to the expansion of the anti-tumor immune response. ICT01 has been shown to have anti-tumor activity against a range of cancers in in vitro and in vivo tumor models.

ImCheck Therapeutics is designing and developing a new generation of immunotherapeutic antibodies targeting butyrophilins, a novel super-family of immunomodulators. As demonstrated by lead clinical-stage program ICT01, which has a mechanism of action to simultaneously modulate innate and adaptive immunity, ImCheck’s “first-in-class” activating antibodies may be able to produce superior clinical results as compared to the first-generation of immune checkpoint inhibitors and, when used in combination, to overcome resistance to this group of agents. In addition, ImCheck’s antagonist antibodies are being evaluated as potential treatments for a range of autoimmune diseases.

Co-founder of the Marseille Immunopole cluster, ImCheck benefits from support from Prof. Daniel Olive (INSERM, CNRS, Institut Paoli Calmettes, Aix-Marseille Université), a worldwide leader in γδ T cells and butyrophilins research; from the experience of an expert management team; and from the commitment of leading US and European investors. For more information, visit http://www.imchecktherapeutics.com.