IMA401 MAGEA4/8 TCER posts 33% ORR in HNSCC with mostly low‑grade CRS and no ICANS

IMA401 is a first-in-class, HLA-A02:01-restricted MAGEA4/8 TCR–based bispecific T-cell engager (TCER) with an Fc for half-life extension and a low-affinity CD3 T-cell–recruiting domain intended to improve tolerability; it was evaluated in the IMA401-101 first-in-human Phase 1a/b basket study (NCT05359445) in heavily pretreated HLA-A02:01+ MAGEA4+ and/or MAGEA8+ recurrent/refractory solid tumors (n=55; median 4 prior lines). Across dose-escalation (0.0066–2.5mg q2w) ± pembrolizumab (n=9), the most common TRAEs were CRS (G1 24%, G2 11%, no ≥G3), transient lymphopenia (any-grade 29%; ≥G3 24%), and neutropenia (any-grade 29%; ≥G3 18%); no ICANS was observed, MTD was not reached (3 DLTs at 2.5mg), and RP2D was set at 1–2mg. In efficacy-evaluable patients treated at ≥1mg (n=38), confirmed responses were seen in head and neck cancer (initial cORR 25% [2/8], then updated post–data cutoff to 33% [4/12]; DCR 63% [5/8]) and melanoma (cORR 29% [2/7]; DCR 57% [4/7]), with all confirmed responses lasting >6 months; in sqNSCLC (n=3), there was 1 PR, 1 SD with OS ~16 months, and 1 PD with liver target-lesion shrinkage. In the post-platinum, post–PD-1 R/M HNSCC setting, single-agent “investigator’s choice” chemo/EGFR therapy is typically low-response (ORR often ~4–14%), so a 33% cORR (even in a biomarker-selected subset) is directionally above historical benchmarks, while the cytopenias/CRS profile looks more like a controllable T-cell engager than classic high-grade CRS/ICANS platforms.