IMA401 Shows Early Clinical Activity in MAGE-A4–Positive Solid Tumors, Supporting Bispecific TCR Development Strategy

Early clinical results presented at the 2026 American Society of Clinical Oncology Annual Meeting and simultaneously published in Nature Medicine are strengthening the case for T-cell receptor (TCR)-based bispecific therapies in solid tumors. Immatics reported updated data from its Phase 1 study evaluating IMA401, a TCR bispecific targeting the cancer-testis antigen MAGE-A4, demonstrating objective responses across multiple tumor types and providing mechanistic evidence supporting the company's broader TCR-T and bispecific combination strategy.¹

The findings highlight growing interest in MAGE-A4 as a target for engineered T-cell therapies and support continued development of the company’s planned IMA401 and IMA402 combination approach.

What did the Phase 1 trial show for IMA401?

IMA401 is a half-life extended TCR bispecific molecule designed to redirect T cells against tumors expressing MAGE-A4 presented on HLA-A*02:01. The ongoing Phase 1 dose-escalation study enrolled heavily pretreated patients with advanced solid tumors, including ovarian cancer, head and neck cancer, non-small cell lung cancer, melanoma, and sarcoma.¹

Among efficacy-evaluable patients treated at active dose levels, investigators observed confirmed objective responses, including partial responses in multiple tumor types. Several patients also achieved durable disease stabilization, contributing to a disease control rate that compares favorably with outcomes typically observed in heavily pretreated solid tumor populations.¹

Researchers reported that responses were associated with robust T-cell activation and expansion, supporting the proposed mechanism of action for the therapy.

According to Immatics, translational analyses demonstrated sustained T-cell engagement within the tumor microenvironment and evidence of anti-tumor immune activity following treatment. These findings provide important biological validation for the company's TCR-based immunotherapy platform.¹

Why is MAGE-A4 emerging as an important target in solid tumors?

MAGE-A4 belongs to a family of cancer-testis antigens expressed across multiple tumor types but largely absent from healthy adult tissues, making it an attractive target for precision immunotherapies.

The antigen is found in a range of difficult-to-treat cancers, including synovial sarcoma, head and neck squamous cell carcinoma, ovarian cancer, non-small cell lung cancer, and melanoma. Because these tumors often exhibit limited responses to existing immunotherapies, researchers have increasingly focused on TCR-based approaches capable of recognizing intracellular tumor antigens that cannot be targeted by conventional antibodies.²

Immatics executives emphasized that the data provide clinical validation not only for IMA401 but also for the broader concept of combining TCR-T cell therapy with TCR bispecifics targeting the same antigen.

“Our data support the continued development of IMA401 and provide a strong foundation for the planned IMA401/IMA402 combination strategy,” the company stated in its ASCO presentation materials.¹

How could the IMA401 and IMA402 combination expand TCR therapy?

A key focus of the presentation involved translational evidence supporting future combination use of IMA401 with IMA402, an investigational adoptive T-cell therapy targeting the same MAGE-A4 antigen.

The rationale centers on using the bispecific molecule to enhance and sustain the activity of transferred T cells after infusion, potentially improving persistence and anti-tumor responses. Researchers believe this approach could address some of the limitations that have historically challenged cellular therapies in solid tumors, including inadequate T-cell expansion and limited durability of response.¹

What safety profile was observed?

Investigators reported that IMA401 demonstrated a manageable safety profile consistent with previous experience for T-cell-engaging therapies. Cytokine release syndrome events were generally low grade and manageable with standard supportive care measures. No unexpected safety signals were identified in the current dataset.¹

As dose escalation and expansion cohorts continue, researchers will seek to further define the therapy’s efficacy, optimal dosing strategy, and potential role in combination regimens.

The ASCO presentation and accompanying Nature Medicine publication add to growing evidence that TCR-based immunotherapies may be capable of extending the reach of precision immuno-oncology beyond traditional checkpoint inhibitors. For patients with MAGE-A4-positive cancers, the findings represent another step toward more targeted treatment options in tumor types that continue to face significant unmet medical need.¹,²

References

1. Immatics Presents Data on IMA401 MAGEA4/8 Bispecific at 2026 ASCO Annual Meeting with Simultaneous Publication in Nature Medicine Supporting Development of IMA401/IMA402 Combination Strategy. (2026 May 31). Immatics. https://www.globenewswire.com/news-release/2026/05/31/3303923/0/en/Immatics-Presents-Data-on-IMA401-MAGEA4-8-Bispecific-at-2026-ASCO-Annual-Meeting-with-Simultaneous-Publication-in-Nature-Medicine-Supporting-Development-of-IMA401-IMA402-Combinatio.html
2. Wermke M, Ochsenreither S, Jaeger D, et al. (2026 May 31). MAGE-A4/MAGE-A8-targeted TCR-based bispecific T cell engager in recurrent and/or refractory solid tumors: a phase 1 trial. Nature Medicine. doi:10.1038/s41591-026-04455-x