Immatics to Present on PRAME-Targeting TCR-T Therapy at 39th SITC Annual Meeting

Immatics N.V., a biopharmaceutical company specializing in T cell-redirecting cancer immunotherapies, has recently announced significant advancements in their clinical and preclinical programs. The company shared an expanded dataset from their ongoing Phase 1b clinical trial for ACTengine® IMA203 and updated Phase 1 data for their next-generation ACTengine® IMA203CD8 TCR-T cell therapy. Additionally, preclinical data on new T cell candidates and combination strategies were presented as part of Immatics’ strategy to target a wider range of solid tumors within its PRAME franchise.

Immatics remains focused on the clinical development of its lead product candidate, IMA203, for patients with second-line or later metastatic melanoma. The company is set to initiate the Phase 3 SUPRAME trial in December, which aims to evaluate IMA203 in 360 patients with unresectable or metastatic melanoma who have previously been treated with a checkpoint inhibitor. This randomized, controlled clinical trial will compare IMA203 to other approved treatments, and the primary endpoint for full approval will be median progression-free survival (PFS). Secondary endpoints include objective response rate, safety, duration of response, and patient-reported outcomes. Patient enrollment is expected to be completed by 2026, with a pre-specified interim analysis planned for early 2026. Immatics targets early 2027 for submitting a Biologics License Application (BLA) for full approval.

The Phase 1b data update for IMA203 included 41 patients treated at the recommended Phase 2 dose, comprising 28 melanoma patients and 13 non-melanoma patients. IMA203 monotherapy has shown a favorable tolerability profile with no treatment-related Grade 5 events among the 70 patients treated across all dose levels and tumor types. The company is on track to commence the SUPRAME trial based on these promising results.

In the Phase 1 dose escalation trial of IMA203CD8 (GEN2), 44 heavily pretreated patients with solid tumors were infused with the therapy across four escalating dose levels. The trial demonstrated that IMA203CD8 maintains a manageable tolerability profile, with most adverse events being related to cytopenia associated with lymphodepletion. Among these patients, deep and durable objective responses were observed, including in hard-to-treat solid tumors with medium-level PRAME copy numbers such as ovarian, endometrial, and triple-negative breast cancer.

Further preclinical studies are underway to enhance the efficacy and durability of Immatics’ TCR-T-based cell therapies targeting PRAME. These studies include the development of TCR-T cells armed with membrane-bound IL-15 (mbIL15) to target tumors with low PRAME copy numbers, such as squamous non-small-cell lung cancer and squamous head and neck cancers. Additionally, Immatics is exploring an allogeneic cell therapy approach to provide next-generation off-the-shelf cell therapies through its ACTallo® platform. These preclinical data were presented during poster sessions at the SITC meeting.

ACTengine® IMA203 is Immatics’ most advanced TCR-based autologous cell therapy, targeting an HLA-A*02-presented peptide derived from preferentially expressed antigen in melanoma (PRAME). This protein is commonly expressed in various solid cancers, making it a promising target for immunotherapy. The peptide was identified using Immatics’ proprietary XPRESIDENT® platform, and a highly specific T cell receptor (TCR) was generated using the XCEPTOR® platform. IMA203 is currently being evaluated in a Phase 1 clinical trial as monotherapy for solid tumors expressing PRAME, including cutaneous melanoma. The upcoming Phase 3 SUPRAME trial will further assess its potential.

Immatics combines the discovery of cancer immunotherapy targets with the development of specific T cell receptors to enable a robust T cell response. This expertise forms the foundation of their pipeline, including Adoptive Cell Therapies and TCR Bispecifics, as well as partnerships with global pharmaceutical leaders. The company is dedicated to utilizing the power of T cells to open new avenues for cancer patients.