Low-dose ICT01 plus low-dose IL-2 safely and significantly increase the number of activated γ9δ2 T cells, CD8 T cells, and Natural Killer cells in patients with solid tumors
Marseille, France, November 11, 2022 – ImCheck Therapeutics presented today the first patient data from EVICTION-2, a Phase I/II clinical trial evaluating the combination of ImCheck’s lead program, ICT01, a γ9δ2 T cell-activating monoclonal antibody targeting BTN3A, combined with low-dose (LD) IL-2, to selectively expand the number of γ9δ2 T cells in relapsed/refractory patients with solid tumors. In a poster presentation at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting being held in Boston, ImCheck researchers and academic collaborators showed data of the combination’s ability to safely and reproducibly induce γ9δ2 T cell activation, expansion, and migration out of the circulation, which was accompanied by similar effects on CD8 T cells and Natural Killer cells (NKs).
In 6 out of 6 evaluable relapsed/refractory ovarian and colorectal cancer patients who had failed >5 lines of treatment, ICT01 (1 or 5 mg IV Day 1 of each cycle) plus LD IL-2 (1 or 2 MIU/m2 SC Days 1-5 of first 3 cycles) increased γ9δ2 T cells 2 to 9 times above baseline during each of the first three 21-day cycles. The combination also demonstrated the activation, mobilization, and proliferation of CD8 T cells and NKs, with slightly more modest effects on granulocytes, in most patients at lower ICT01 doses than shown in previously presented data of ICT01 monotherapy in a similar patient population (EVICTION trial). The safety profile for the combination exhibited no dose-limiting toxicities in the first 3 dose cohorts and tolerability remained consistent without any new or increased adverse reactions.
“The data presented today provide initial clinical evidence that ICT01 plus LD IL-2 can significantly increase the number of γ9δ2 T cells and other important immune cell populations that could generate a stronger anti-tumor immune response in heavily pre-treated solid tumor patients,” commented Paul Frohna, MD, PhD, Chief Medical Officer at ImCheck Therapeutics. “The combination’s safety profile is a positive outcome and is firmly in line with the results for ICT01 monotherapy and in combination with pembrolizumab that we have seen from over 100 cancer patients who have participated in the ongoing EVICTION trial.”
About the EVICTION-2 Trial
EVICTION-2 is a first-in-human, dose escalation (Part 1) and cohort expansion (Part 2) clinical trial evaluating ICT01 in combination with low dose subcutaneous IL-2. The trial’s objective is to demonstrate the combination’s ability to selectively expand the number of γ9δ2 T cells in patients with solid tumors (prostate, pancreatic, ovarian, or colorectal cancer). For more information, please refer to https://clinicaltrials.gov and reference NCT05307874.
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 (e.g., leukemia & lymphoma) 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.
As demonstrated in EVICTION data presented at past AACR, EMSO and SITC conferences, ICT01 selectively activates circulating γ9δ2 T cells that leads to migration of γ9δ2 T cells out of the circulation and into target tissue (e.g., 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, IFNγ and TNFα, 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.
About IMCHECK THERAPEUTICS
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 γ9δ2 T cells and butyrophilins research; from the experience of an expert management team; and from the commitment of leading US and European investors.
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