New MAGE-A4/8 TCR-based TCER shows encouraging activity at RP2D in phase 1 solid-tumor trial
IMA401 is a TCR-based bispecific T cell engager that targets an HLA-A*02:01-presented MAGE-A4/8 peptide to recruit T cells and kill tumor cells. In a first-in-human phase 1 basket trial across 61 patients with MAGE-A4/8-positive solid tumors, the maximum tolerated dose was not reached and the RP2D was defined as 1–2 mg biweekly. TRAEs were common but manageable, led by cytokine release syndrome (mostly grade 1–2), lymphopenia and neutropenia; five DLTs occurred (neutropenia), with no DLTs at RP2D when dexamethasone premedication was used. Across efficacy-evaluable patients, confirmed ORR was 14% overall and 20% at RP2D, with higher activity in head and neck cancers (29%). One possibly related death occurred at 2.5 mg without premedication. In pembrolizumab expansion cohorts, tolerability matched monotherapy. PK showed a median half-life of ~17.5 days. These results support continued development of this half-life extended TCR-based TCER platform across diverse solid tumors.