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

Area of Science:

• Oncology
• Immunotherapy
• Drug Development

Background:

• IMA401 is a novel bispecific T cell engaging receptor (TCER) designed for advanced solid tumors.
• It targets a MAGE-A4/MAGE-A8 peptide presented by HLA-A*02:01.
• The therapy incorporates a high-affinity TCR-based domain, a low-affinity T-cell-recruiting domain, and an optimized Fc domain for extended half-life.

Purpose of the Study:

• To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of IMA401.
• To evaluate the safety and tolerability of IMA401, alone and in combination with pembrolizumab.
• To assess the antitumor activity and pharmacokinetics of IMA401.

Main Methods:

• A phase 1, first-in-human trial involving 61 patients with advanced solid tumors.
• Patients received intravenous IMA401 at doses ranging from 0.0066 mg to 2.5 mg, with or without pembrolizumab.
• Primary endpoints included MTD and RP2D determination; secondary endpoints focused on safety, tolerability, antitumor activity, and pharmacokinetics.

Main Results:

• The MTD was not reached; the RP2D was established at 1-2 mg IMA401 biweekly.
• Treatment-related adverse events were manageable, with cytokine release syndrome, lymphopenia, and neutropenia being most common.
• An objective response rate (ORR) of 14% was observed overall, with 20% ORR at the RP2D across various indications. Head and neck cancer patients at RP2D showed a 29% ORR.

Conclusions:

• IMA401 demonstrates a manageable safety profile with mostly transient adverse events.
• The bispecific TCER platform shows promising antitumor activity at the recommended phase 2 dose.
• IMA401 is a potential therapeutic option for advanced solid tumors, with or without pembrolizumab.