Immatics presents TCER IMA401 data at ESMO

Immatics presented the proof-of-concept clinical data for the first candidate of its next-generation, half-life extended TCR Bispecifics platform, TCER IMA401, during an oral presentation at the European Society for Medical Oncology, or ESMO, Congress 2024. Initial data from the IMA401 Phase 1a first-in-human dose escalation basket trial in a broad range of heavily pretreated patients with recurrent and/or refractory solid tumors showed initial anti-tumor activity, durable objective responses, including confirmed responses ongoing at 13+ months, and a manageable tolerability profile. As of data cut-off on July 23, 35 heavily pretreated patients with recurrent and/or refractory solid tumors have been treated with IMA401 monotherapy across nine escalating dose levels. The treated patient population is composed of patients with 16 different solid tumor indications who are both HLA-A*02:01 and MAGEA4/8-positive, had received a median of four and up to eight lines of prior systemic treatments and the majority have an ECOG performance status of 1. The safety population includes all 35 patients treated with IMA401. 29 patients were evaluable for efficacy analysis, of which 17 patients were treated at relevant dose and target levels. IMA401 demonstrated an overall manageable tolerability profile in the 35 patients treated. The most frequent treatment-related adverse events, or AEs, were transient lymphopenia and mild to moderate cytokine release syndrome, or CRS, with the majority of CRS occurring at the first dose. Both AEs are consistent with the proposed mechanism of action and reported for other bispecific T cell engagers. Neutropenia was also observed at high dose levels and occurred mostly at the initial target dose in patients with and without dexamethasone pre-medication. High-grade neutropenia was fully resolved in all cases except one. Dose escalation for the trial is ongoing and the maximum tolerated dose has not yet been determined. IMA401 demonstrated an “antibody-like” median half-life of over two weeks. This supported the switch to q2w dosing during dose escalation. In addition, the data support pursuing increased dosing intervals of up to q4w, which could further offer an ideal dosing interval for potential combination with checkpoint inhibitors. IMA401 demonstrates initial anti-tumor activity in multiple tumor types. As of data cut-off on July 23, three of four confirmed responses were ongoing at 13+, 8+ and 3+ months. Deep responses were observed in four patients. The data obtained also indicate that objective responses are associated with MAGEA4/8 target expression level.