Immatics’ PRAME-Targeted TCR Bispecific IMA402 Shows 32% Response Rate in PRAME-High Tumors

Immatics’ IMA402, a T-cell receptor (TCR)-based bispecific T-cell engager targeting the cancer antigen PRAME, produced a 32% confirmed response rate in patients with high PRAME expression in a phase 1b trial, according to data presented at the European Society for Medical Oncology (ESMO) Congress 2026.¹ In patients with PRAME-high melanoma, 91% were alive at one year when treated within the recommended phase 2 dose (RP2D) range.¹

“The data presented at ESMO further underscore the potential of IMA402 as an off-the-shelf treatment option for patients with solid cancers,” said Cedrik Britten, MD, PhD, chief medical officer at Immatics.¹

How does IMA402 work?

PRAME is a cancer testis antigen that is expressed in many tumor types, including melanoma, ovarian cancer, and lung cancer, but has limited expression in healthy adult tissues outside the testis.² Because PRAME is located inside the cell, it cannot be reached by conventional antibodies.² Instead, fragments of the protein are presented on the cell surface by human leukocyte antigen (HLA) class I molecules, where T cells can recognize them.²

IMA402 is built on Immatics’ TCER platform. One arm uses an engineered TCR to bind a PRAME-derived peptide presented on HLA-A*02:01, and the other binds CD3 to recruit and activate T cells.¹ Patients are selected using a proprietary blood-based PRAME test.¹

The approach has precedent. In 2022, FDA approved Immunocore’s tebentafusp (Kimmtrak), the first TCR therapeutic and the first bispecific T-cell engager approved for a solid tumor, for uveal melanoma in HLA-A*02:01-positive patients.³

What did the phase 1b trial show?

As of a June 1, 2026 data cutoff, 126 heavily pretreated patients had received at least one infusion of IMA402, with a median of three prior lines of therapy.¹ Among 40 efficacy-evaluable patients treated at the RP2D range of 10 to 45 mg, the confirmed objective response rate was 25% and the disease control rate was 63%.¹

In the 31 patients with PRAME-high tumors, the confirmed response rate was 32%.¹ In PRAME-high melanoma, seven of 22 patients responded, including one confirmed complete response, and the median duration of response was 12.5 months.¹ Median overall survival had not been reached, and one-year survival was 91%, compared with 60% in patients treated below the RP2D range.¹ Three of six patients with PRAME-high ovarian cancer also responded.¹

The most frequent treatment-related adverse events were transient lymphopenia and low-grade cytokine release syndrome.¹ No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) or IMA402-related deaths were reported.¹ The results come from an uncontrolled study, and the company noted that all data are preliminary.¹

Why target peptide-MHC complexes?

T-cell engagers have had limited success in solid tumors because few surface proteins are expressed on tumors but not healthy tissue. In a BioPharm International® Q&A, Johanna Kaufmann, PhD, chief scientific officer of Deck Bio, said that “T cell engagers have so far been restricted to niche indications” and explained that targeting peptide-MHC complexes can open up intracellular proteins that are expressed almost exclusively in tumors.

Immatics also presented data at ESMO for IMA203CD8, an engineered TCR T-cell therapy that targets PRAME, which showed a 55% response rate in 20 patients with gynecologic cancers treated at clinically relevant doses.¹

What happens next?

Immatics plans to evaluate IMA402 in combination with immune checkpoint inhibitors in melanoma and gynecologic cancers, and no additive toxicity has been observed with that combination to date.¹ First data for IMA402 combined with IMA401, the company’s MAGEA4/8-targeted TCR bispecific, in lung cancer are expected in 2027.¹ The company is also considering a fast-to-market strategy in PRAME-high melanoma.¹

References

1. Immatics presents clinical activity of IMA402 PRAME bispecific and IMA203CD8 PRAME cell therapy across advanced solid tumors in two oral presentations at 2026 ESMO Annual Meeting. News release. Immatics N.V. October 24, 2026. Accessed October 27, 2026.
2. Al-Khadairi G, Decock J. Cancer testis antigens and immunotherapy: where do we stand in the targeting of PRAME? Cancers (Basel). 2019;11(7):984. doi:10.3390/cancers11070984
3. Immunocore announces FDA approval of KIMMTRAK® (tebentafusp-tebn) for the treatment of unresectable or metastatic uveal melanoma. News release. Immunocore. January 26, 2022. Accessed October 27, 2026.