Emmanuel Valentin presented the culmination of five years’ clinical development of ICT01, a first-in-class monoclonal antibody targeting BTN3A, designed to activate a rare subset of T cells known as γ9δ2 T cells. These cells, which comprise a small fraction of the CD3 compartment, act as a bridge between innate and adaptive immunity and are crucial for immunosurveillance and anti-tumour activity. Valentin explained that BTN3A is upregulated in stressed or cancerous cells, and ICT01’s engagement with this target triggers γ9δ2 T cell activation and proliferation, alongside the production of pro-inflammatory cytokines and cytotoxic actions against malignant cells.
The clinical programme, named EVICTION, was an open-label phase 1/2a trial conducted across multiple centres in Europe and the US. It tested ICT01 both as monotherapy and in combination with pembrolizumab or venetoclax and azacitidine (Ven-Aza), enrolling patients with advanced solid and haematological tumours. Valentin highlighted the trial’s classical dose escalation and expansion design, with cohorts spanning various cancer types, including AML, FL, DLBCL, melanoma, bladder, lung, and neck cancers.
Safety findings were particularly favourable, with only mild infusion reactions and cytokine release syndrome observed, and no grade 4 or 5 toxicities. This profile held true across both monotherapy and combination arms, in solid and liquid tumours. Most adverse events occurred during the first dosing cycle and were related to both ICT01 dose and baseline γ9δ2 T cell numbers.
Valentin reported encouraging efficacy signals, especially in first-line AML patients treated with ICT01 plus venetoclax and azacitidine. The low-dose group achieved an unprecedented composite complete response rate of 84%, with efficacy observed even in adverse molecular subtypes. These results compare favourably with historical data and have led to orphan drug and fast track designations, as well as positive feedback from regulatory authorities. The recommended phase 2 dose is now established, and ongoing work focuses on biomarker-driven patient enrichment and stratification, with comprehensive sampling and analysis of blood and tumour biopsies to support further development.
