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

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

  • By

  • Martin Wermke

  • Sebastian Ochsenreither

  • Dirk Jaeger

  • Heiko Becker

  • Annalen Bleckmann

  • Farastuk Bozorgmehr

  • Manik Chatterjee

  • Stefanie Groepper

  • Mathias Haenel

  • Judith S. Hecker

  • Max-Felix Häring

  • Daniel Heudobler

  • Norbert Hilf

  • Martin Hofmann

  • Meike Hutt

  • Andrea Mayer-Mokler

  • Sarah Missel

  • Manuel Ruh

  • Heiko Schuster

  • Olga Veremchuk

  • Moritz Kleemiss

  • Stefan Knop

  • Simon Laban

  • Martin Sebastian

  • Silvia Spoerl

  • Cedrik Michael Britten

  • Carsten Reinhardt

  • May 31, 2026

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Clinical Report: Targeting MAGE-A4 and MAGE-A8 with TCR-based Bispecific T Cell Engagers

Overview

This report presents findings from a Phase 1 study evaluating IMA401, a TCR-based bispecific T cell engager targeting MAGE-A4 and MAGE-A8 in patients with advanced solid tumors.

Background

Bispecific T cell engagers (TCEs) have shown success in hematologic malignancies but face challenges in solid tumors, including low target specificity and rapid clearance. IMA401, a next-generation TCR-based TCE, aims to overcome these limitations by targeting intracellular antigens presented on HLA class I molecules, specifically MAGE-A4 and MAGE-A8.

Data Highlights

No numerical data available in the provided material.

Key Findings

  • IMA401 targets an HLA-A*02:01-presented peptide derived from MAGE-A4 and MAGE-A8.
  • The selected target peptide shows at least five-fold higher presentation levels on tumor cells compared to a commonly used MAGE-A4-derived epitope.
  • MAGE-A4/8 gene expression is prevalent in solid tumors, particularly in squamous cell NSCLC (65%) and HNSCC (45%).
  • Initial antitumor activity was observed in heavily pretreated patients, with manageable adverse events including low-grade cytokine release syndrome.
  • IMA401 combines a high-affinity TCR domain with a low-affinity T-cell-recruiting domain for enhanced T cell activation.

Clinical Implications

The findings suggest that IMA401 may provide a new therapeutic option for patients with advanced solid tumors expressing MAGE-A4 and MAGE-A8. Ongoing development and further studies will help clarify its role in the treatment landscape.

Conclusion

The Phase 1 study of IMA401 reports initial findings on its use as a TCR-based bispecific T cell engager for targeting MAGE-A4 and MAGE-A8 in advanced solid tumors.

Related Resources & Content

  1. Immatics, Nasdaq, 2024 -- Immatics Presents Clinical Proof-of-Concept Data from Ongoing Phase 1 Dose Escalation Trial with TCR Bispecific Molecule TCER® IMA401 Targeting MAGEA4/8
  2. The ASCO Post — Bispecific Antibody Recruitment to Increase Antitumor Activity of Adoptive T-Cell Transfer
  3. The ASCO Post — Early-Phase Study Explores CAR T-Cell Therapy for Relapsed or Refractory B-Cell Lymphoma
  4. The ASCO Post — FDA Pipeline: Breakthrough Therapy Designation in Lung Cancer, Orphan Drug Designations in Myeloma and Soft-Tissue Sarcoma
  5. Frontiers in Oncology — Targeting solid tumors with TCR-T cells: mechanisms, progress, and challenges
  6. Targeting solid tumors with TCR-T cells: mechanisms, progress, and challenges
  7. Uveal melanoma: ESMO–EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up - ScienceDirect
  8. Immatics Presents Clinical Proof-of-Concept Data from Ongoing Phase 1 Dose Escalation Trial with TCR Bispecific Molecule TCER® IMA401 Targeting MAGEA4/8 at ESMO 2024 and Provides Development Update | Nasdaq
  9. Definition of anti-MAGE-A4 T-cell receptor/anti-CD3 scFv fusion protein IMC-C103C - NCI Drug Dictionary - NCI

Original Source(s)

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

  • by Martin Wermke, Sebastian Ochsenreither, Dirk Jaeger, Heiko Becker, Annalen Bleckmann, Farastuk Bozorgmehr, Manik Chatterjee, Stefanie Groepper, Mathias Haenel, Judith S. Hecker, Max-Felix Häring, Daniel Heudobler, Norbert Hilf, Martin Hofmann, Meike Hutt, Andrea Mayer-Mokler, Sarah Missel, Manuel Ruh, Heiko Schuster, Olga Veremchuk, Moritz Kleemiss, Stefan Knop, Simon Laban, Martin Sebastian, Silvia Spoerl, Cedrik Michael Britten, Carsten Reinhardt

  • May 31, 2026

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