822O - Activation of γ9δ2 T cells by ICT01 as a novel immunotherapeutic approach for relapsed/refractory hematologic cancers (EVICTION trial)

Background

ICT01, an anti-BTN3A targeted mAb that selectively activates γ9δ2 T cells, is being studied in the ongoing phase 1/2a EVICTION Trial in advanced solid and hematologic cancers (NCT04243499). ICT01-activated γ9δ2 T cells are known to kill acute myeloid leukemia blasts and lymphoma cell lines both in vitro and in vivo, making γ9δ2 T cells of interest as a novel immunotherapeutic strategy against hematologic cancers. Here we present data from the EVICTION phase 1 in relapsed/refractory hematological cancers.

Methods

Patients with hematologic cancers who failed available standard of care received IV ICT01 alone (200 μg to 75 mg) every 21 days. Antitumor assessment by imaging or bone marrow analysis was done every 8 weeks after using the Response Evaluation Criteria in Lymphoma (RECIL) and IWG Criteria for AML. Safety reviews were conducted prior to dose escalation. Disease Control Rate (DCR) was the primary efficacy endpoint and defined as the sum of complete response (CR), CR with incomplete recovery (CRi), partial response (PR) and stable disease (SD). Blood samples were collected for pharmacokinetic and pharmacodynamic analyses.

Results

Dose escalation was completed with 26 patients (1 Diffuse Large B-cell Lymphoma, 1 Follicular Lymphoma, 24 AML), with no dose-limiting toxicities and a good safety profile similar to that in solid tumors. First-dose infusion-related reaction, nausea, fever and vomiting (Grade 1/2) were the most common treatment-related AEs. Only 2 Grade 3 events of neutropenia were reported and resolved with continued treatment. Target occupancy on circulating T cells ≥ 30% was observed 30 min post doses ≥ 700 μg, with activation and migration of >95% γ9δ2 T cells from the blood within 24hrs of dosing. Ten of 26 patients were evaluable at week 8 with an observed DCR of 30%. One DLBCL patient still receiving ICT01 at 7 mg has had a PR from Wk 40 to Wk 94/C32. In the 20 mg dose group, two AML patients achieved stable disease at week 8 with one still on study at Wk 53/C19.

Conclusions

The good safety profile and encouraging clinical activity data in these last-line patients support further testing of ICT01 in a first-line AML phase 2a expansion cohort in combination with VEN/AZA in EVICTION that will start mid-2023.

Clinical trial identification

EudraCT 2019-003847-31; NCT04243499.

Editorial acknowledgement

Legal entity responsible for the study

ImCheck Therapeutics.

Funding

ImCheck Therapeutics.

Disclosure

S. Garciaz: Financial Interests, Personal, Advisory Role: AbbVie, Astellas, Novartis, Amgen. S. Champiat: Financial Interests, Personal, Invited Speaker: Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck, Merck Serono, Novartis and Roche; Financial Interests, Personal, Other, Principal Investigator of Clinical Trials: AbbVie, Amgen, Boehringer Ingelheim, Cytovation, Eisai, Imcheck Therapeutics, Molecular Partners Ag, Merck, Ose Pharma, Pierre Fabre, Sanofi Aventis, SOTIO A.S, Transgene; Financial Interests, Personal, Advisory Board: Alderaan Biotechnology, Amgen, AstraZeneca, Avacta, Celanese, Domain Therapeutics, Ellipses Pharma, Genmab, Immunicom, Inc., Nanobiotix, Nextcure, Oncovita, Pierre Fabre, Seagen, Tatum Bioscience, Tollys SAS, UltraHuman8; Financial Interests, Personal, Other, Travel and congress: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Ose Pharma, Roche, SOTIO; Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP)=Principal/sub-Investigator of Clinical Trials: Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Adaptimmune, AdlaiAstex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd., Bayer Healthcare Ag, Bbb Technologies Bv, BeiGene, BicycleTx Ltd., Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Casi Pharmaceuticals, Inc, Celgene Corporation, Cellcentric, Chugai Pharmaceutical Co, Cullinan-Apollo, Curevac, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd., Forma Tharapeutics, Gamamabs, Genentech, GSK, H3 Biomedicine, F. Hoffmann-La Roche AG, Imcheck Therapeutics, Incyte Corporation, Imcheck Therapeutics, Incyte Corporation, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium SA, Janssen Cilag, Janssen Research Foundation, Janssen R&D LLC, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Genomics, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre Medicament, Relay Therapeutics, Inc., Roche, Sanofi Aventis, Seattle Genetics, SOTIO A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Transgene S.A, Turning Point Therapeutics, Xencor; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP) =Research Grants: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Product Samples, As part of the Drug Development Department (DITEP) =Non-financial support (drug supplied): AstraZeneca, BMS, Boehringer Ingelheim, GSK, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche. K. Lemmens, A. de Gassart, P. Brune, E. Valentin, P.A. Frohna: Financial Interests, Personal, Full or part-time Employment: ImCheck Therapeutics. D. Olive: Financial Interests, Personal, Advisory Board, Shareholder: ImCheck Therapeutics. All other authors have declared no conflicts of interest.