What question did this study set out to answer?

To evaluate the safety and antitumor efficacy of IMA401, a bispecific T cell engager, in patients with recurrent solid tumors.

June 3, 2026Nature Medicine0 citationsOpen Access

MAGE-A4/MAGE-A8-targeted TCR-based bispecific T cell engager in recurrent and/or refractory solid tumors: a phase 1 trial

MWMartin Wermke SOSebastian Ochsenreither DJDirk Jaeger

Key Points

To evaluate the safety and antitumor efficacy of IMA401, a bispecific T cell engager, in patients with recurrent solid tumors.
Phase 1 trial involving 61 patients with advanced solid tumors receiving IMA401 intravenously.
Primary endpoint focused on determining the maximum tolerated dose and recommended phase 2 dose.
Secondary objectives included assessing safety, tolerability, and pharmacokinetics.
Maximum tolerated dose was not reached, with a recommended phase 2 dose of 1-2 mg of IMA401 biweekly.
Overall objective response rate was 14% (8/56), increasing to 20% (8/41) at the RP2D.
In head and neck cancer patients, the objective response rate was 29% (4/14), with a median duration of response of 8.8 months.

Abstract

IMA401 is a T cell receptor (TCR)-based next-generation bispecific T cell engaging receptor (TCER) targeting an HLA-A*02:01-presented peptide derived from MAGE-A4/MAGE-A8 with its high-affinity TCR-based domain, incorporating a low-affinity T-cell-recruiting domain and an optimized Fc domain to prolong half-life. In this prespecified interim analysis of a phase 1 first-in-human trial, 61 patients with advanced solid tumors received intravenous IMA401 (0.0066 mg-2.5 mg) with or without pembrolizumab. The primary endpoint was determination of the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of IMA401 monotherapy and in combination with pembrolizumab. Secondary objectives included safety and tolerability, antitumor activity and pharmacokinetics. The MTD was not reached as defined by the clinical trial protocol, and the RP2D was 1-2 mg IMA401 biweekly. Treatment-related adverse events (TRAEs) were well manageable; the most common any-grade TRAEs were cytokine release syndrome (38%, grades 1-2 only), transient lymphopenia (33%) and reversible neutropenia (31%). Five patients experienced dose-limiting toxicity (DLT) events primarily related to neutropenia. No further DLTs occurred in the RP2D range with dexamethasone premedication. One possibly-related death (pneumonia in a patient with rapidly progressing lung metastases) was reported outside RP2D at 2.5 mg IMA401. In the overall efficacy-evaluable population across all dose levels (n = 56), including low starting doses (from 0.0066 mg), the confirmed objective response rate (ORR) was 14% (8/56). In patients receiving IMA401 at the RP2D, an ORR of 20% (8/41) was observed across 15 different indications (post hoc analysis). In the largest subgroup of patients treated at RP2D, namely head and neck cancer, the ORR was 29% (4/14) with a median duration of response of 8.8 months. These findings show that the bispecific TCER platform has a manageable safety profile with mostly transient adverse events and promising antitumor activity at the RP2D of IMA401 with or without pembrolizumab. ClinicalTrials.gov identifier: NCT05359445 .

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