- Broad antitumor immune responses and demonstration of sturdy illness management from stable tumor sufferers who beforehand failed a number of checkpoint-inhibitor routine, throughout a spread of ICT01 doses together with pembrolizumab
- ICT01 demonstrated a good and constant security and tolerability profile with out dose-limiting toxicities together, in keeping with monotherapy outcomes
ImCheck Therapeutics right this moment introduced promising up to date security and affected person response knowledge from the accomplished dose escalation mixture cohort of its ongoing EVICTION medical trial throughout an oral session at the European Society for Medical Oncology (ESMO) Congress presently being held in Paris, France. EVICTION is an open-label Phase I/IIa research evaluating ImCheck’s lead antibody ICT01 as a monotherapy in each stable tumor and hematological cancers, and together with pembrolizumab in stable tumors.
Results from the Phase I dose-escalation, mixture cohorts (n=40 throughout 6 dose ranges) demonstrated that remedy with ICT01 plus pembrolizumab induced illness management in 42% of melanoma (5/12), 22% of non-small-cell lung carcinoma (4/18), 22% of bladder most cancers (2/9) sufferers and in 1 head and neck squamous cell carcinoma (HNSCC) affected person, (1/1) as decided by RECIST1.1 standards. All sufferers handled had beforehand failed at the very least one checkpoint inhibitor (CPI) routine, which underscores the potential of ICT01 mixture remedy as a novel choice for relapsed/refractory sufferers post-CPI remedy, which stays a major unmet medical want. Two partial responses had been achieved in melanoma sufferers who reached follow-up past 6 and 16 months, with the latter affected person additionally attaining a sturdy full regression of a mind metastasis from 6 months onward. The broad antitumor response knowledge counsel that larger baseline circulating γ9δ2 T cell ranges correlate with higher remedy outcomes. This helps the deliberate affected person enrichment technique using decrease baseline γ9δ2 T cell counts, as in comparison with ICT01 monotherapy, for eligibility in the upcoming Phase IIa mixture teams of sufferers with CPI-refractory melanoma, chemotherapy-resistant bladder most cancers, or CPI-refractory HNSCC.
“The data presented today demonstrate that the complementary mechanisms of action for ICT01 and pembrolizumab alter the tumor microenvironment to generate clinical responses against multiple CPI-resistant solid tumors,” commented Paul Frohna, MD, PhD, Chief Medical Officer at ImCheck Therapeutics. “It is encouraging to see a continued good safety profile for ICT01 in the combination setting in addition to robust activation of γ9δ2 T cells that promote tumor infiltration of CD8 and NK cells, which can be fully unleashed to attack the cancerous cells by concomitant PD-1 blockade.”
Pierre d’Epenoux, Chief Executive Officer of ImCheck Therapeutics added: “With these positive data, we further substantiate the potential of ICT01 as a novel, differentiated therapeutic approach for a broad population of cancer patients. We feel confident that we have achieved our goals for the first part of the EVICTION trial, both in monotherapy with cohort expansion already underway and in combination with pembrolizumab. We eagerly anticipate exciting clinical efficacy results from the Phase IIa next year.”
The oral presentation, titled “The Combination of ICT01, a γ9δ2 T cell-activating mAb, plus Pembrolizumab Induces a Broad Antitumor Immune Response and Disease Control in Patients with CPI-Failure Melanoma, NSCLC and Bladder Cancer: EVICTION Trial”, was given by Dr. Stéphane Champiat, lead research investigator of the EVICTION trial at the Gustave Roussy Cancer Center, Paris, France. The knowledge was introduced throughout the investigational immunotherapy session from 14:45 to 16:15 CEST on Saturday September 10, 2022.
***
About the EVICTION Trial
EVICTION is a first-in-human, dose escalation (Part 1) and cohort enlargement (Part 2) medical trial of ICT01 in sufferers with varied superior relapsed or refractory stable or hematologic cancers which have exhausted customary of care remedy choices. Part 1 is a basket trial designed to characterize the preliminary security, tolerability, and pharmacodynamic exercise of ICT01 as monotherapy (Group A: stable tumors; Group B: hematologic tumors) and together with pembrolizumab (Group C: stable tumors). Group A contains bladder, breast, colorectal, gastric, melanoma, ovarian, prostate, and pancreatic most cancers sufferers, Group B contains acute myeloid leukemia, acute lymphocytic leukemia, follicular lymphoma, and diffuse giant B cell lymphoma sufferers, and Group C contains bladder, head and neck squamous cell carcinoma, melanoma, and non-small cell lung most cancers sufferers. Basket trials are a medical trial design that enables new medication to be examined quickly in a spread of indications, offering preliminary knowledge on a number of parameters that may contribute to an accelerated growth timeline. Part 2 of the trial is a Phase II cohort enlargement research in chosen indications as each monotherapy and together. First indications chosen for the Phase II monotherapy enlargement cohorts are relapsed/refractory ovarian most cancers and metastatic castrate-resistant prostate most cancers. More data on the EVICTION trial could be discovered at clinicaltrials.gov (NCT04243499). A second medical trial, EVICTION-2, evaluating the mixture of ICT01 plus low dose subcutaneous IL-2 to selectively develop the variety of γ9δ2 T cells in sufferers with stable tumors (prostate, pancreatic, ovarian, or colorectal most cancers) can be ongoing (NCT05307874).
About ICT01
ICT01 is a humanized, anti-BTN3A (also called CD277) monoclonal antibody that selectively prompts γ9δ2 T cells, that are a part of the innate immune system that’s chargeable for immunosurveillance of malignancy and infections. The 3 isoforms of BTN3A focused by ICT01 are overexpressed on a lot of stable tumors (e.g., bladder, colorectal, melanoma, ovarian, pancreatic, lung) and hematologic cancers (e.g., leukemia & lymphoma) and additionally expressed on the floor of innate (e.g., γδ T cells and NK cells) and adaptive immune cells (T cells and B cells). BTN3A is crucial for the activation of the anti-tumor immune response of γ9δ2 T cells.
As demonstrated in EVICTION knowledge introduced at previous AACR, EMSO and SITC conferences, ICT01 selectively prompts circulating γ9δ2 T cells that results in migration of γ9δ2 T cells out of the circulation and into goal tissue (e.g., tumors), whereas additionally activating the tumor-resident γ9δ2 T cells to immediately kill malignant cells, which is accompanied by secretion of two key inflammatory cytokines, IFNγ and TNFα, that contribute to the enlargement of the anti-tumor immune response. ICT01 has been proven to have anti-tumor exercise in opposition to a spread of cancers in in vitro and in vivo tumor fashions.
About IMCHECK THERAPEUTICS
ImCheck Therapeutics is designing and growing a brand new technology of immunotherapeutic antibodies concentrating on butyrophilins, a novel super-family of immunomodulators.
As demonstrated by lead clinical-stage program ICT01, which has a mechanism of motion to concurrently modulate innate and adaptive immunity, ImCheck’s “first-in-class” activating antibodies could possibly produce superior medical outcomes as in comparison with the first-generation of immune checkpoint inhibitors and, when utilized in mixture, to beat resistance to this group of brokers. In addition, ImCheck’s antagonist antibodies are being evaluated as potential therapies for a spread of autoimmune ailments.
Co-founder of the Marseille Immunopole cluster, ImCheck advantages from assist from Prof. Daniel Olive (INSERM, CNRS, Institut Paoli Calmettes, Aix-Marseille Université), a worldwide chief in γ9δ2 T cells and butyrophilins analysis; from the expertise of an knowledgeable administration group; and from the dedication of main US and European buyers.
For additional data: https://www.imchecktherapeutics.com/ and @ImCheckThx
Press contacts
US and EU
Trophic Communications
Gretchen Schweitzer
+49 (0) 172 861 8540
[email protected]
France
ATCG PARTNERS
Céline Voisin
+33 (0)9 81 87 46 72 / +33 (0)6 62 12 53 39
[email protected]
- PR in English
- ESMO presentation
