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

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. 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. 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. 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.