Immatics Reports Clinical Activity for Two PRAME Cancer Therapies

HOUSTON, Texas, and TÜBINGEN, Germany — October 24, 2026

IMA402 Shows Durable Responses in PRAME-High Melanoma

IMA402 is an investigational TCR bispecific designed to recognize a PRAME-derived peptide presented by HLA-A*02:01 on tumor cells and direct an immune response against cancer. In the ongoing Phase 1b study (NCT05958121), 126 heavily pretreated patients across multiple tumor types had received at least one infusion by the June 1, 2026, data cutoff. Patients had received a median of three prior lines of systemic therapy. The efficacy analysis at the recommended Phase 2 dose range of 10 to 45 mg included 40 patients, of whom 31 had PRAME-high tumors. Across this 40-patient population, IMA402 achieved a 25% cORR (10 of 40 patients) and a disease control rate of 63% (25 of 40). One confirmed complete response occurred in a patient with melanoma, and the longest ongoing response exceeded two years. Among patients with PRAME-high tumors, the cORR was 32% across indications. In the PRAME-high melanoma subgroup, seven of 22 patients responded, corresponding to a cORR of 32%, while median DOR reached 12.5 months after a median follow-up of 16.8 months. Median overall survival had not been reached at a median follow-up of 8.8 months, and 91% of patients were alive at one year. All patients with PRAME-high melanoma had previously received immune checkpoint inhibitors, while all patients with PRAME-high ovarian cancer had received platinum-based chemotherapy. Among six patients with PRAME-high ovarian cancer, three confirmed responses were reported. The safety profile was characterized by expected, transient lymphopenia and low-grade cytokine release syndrome (CRS). No immune effector cell-associated neurotoxicity syndrome (ICANS) or IMA402-related Grade 5 events were reported. The company also reported no additive toxicity when IMA402 was combined with an immune checkpoint inhibitor in the evaluated patients. Immatics plans to pursue development across melanoma, gynecologic cancers and lung cancer, including combinations with immune checkpoint inhibitors and its MAGEA4/8-directed bispecific IMA401. Initial data from the planned lung cancer combination approach are expected in 2027. The company is also evaluating rapid liquid biopsy-based PRAME testing to support patient selection, subject to further validation and regulatory requirements.

IMA203CD8 Demonstrates Activity Across PRAME-Positive Tumors

IMA203CD8 is an investigational PRAME-directed TCR T-cell therapy engineered to recognize a PRAME-derived peptide presented by HLA-A*02:01. The therapy incorporates CD8αβ co-transduction intended to enhance the activity of the engineered T cells. In the ongoing Phase 1 study (NCT03686124), 98 heavily pretreated patients with advanced PRAME-expressing solid tumors had been enrolled by the August 7, 2026, data cutoff. Of these, 90 patients were evaluable for efficacy across gynecologic cancers, melanoma, synovial sarcoma and other tumor types. Across evaluated dose levels, a one-time infusion produced an overall response rate (ORR) of 51% (46 of 90 patients) and a cORR of 41% (36 of 87 patients). The disease control rate was 82%, and 83% of patients with evaluable target lesions experienced tumor reduction. Responses were observed across several tumor types, and ongoing responses lasting more than 2.5 years were reported. In a subgroup of 20 patients with ovarian or uterine cancer treated at clinically relevant dose levels, the ORR was 60% and the cORR was 55% (11 of 20 patients). The disease control rate was 70%, while tumor reduction was observed in 68% of patients with evaluable target lesions. Median DOR was 8.4 months at a median follow-up of 6.0 months, and median progression-free survival was 5.8 months at a median follow-up of 8.1 months. Median overall survival had not been reached at a median follow-up of 7.8 months. IMA203CD8 showed a manageable safety profile across the evaluated dose range. Common treatment-emergent adverse events included transient cytopenias associated with the lymphodepletion regimen and low-grade CRS. ICANS was infrequently observed, no IMA203CD8-related Grade 5 events occurred, and the maximum tolerated dose had not been reached at doses up to 12.5 billion cells. Immatics has completed Phase 1a dose escalation and is enrolling patients with uterine cancer at clinically relevant doses. A Phase 1/2 investigator-initiated trial in PRAME-positive pediatric cancers is planned for the first half of 2027. The company intends to build evidence through selected tumor cohorts, including ovarian, uterine, rare and pediatric cancers, to assess the potential for broader tumor-agnostic development.

Immatics Advances a Broader PRAME-Targeting Strategy

The updated findings support Immatics’ strategy of pursuing multiple therapeutic approaches against PRAME, a tumor-associated target expressed across more than 50 cancers, according to the company. Its PRAME-focused pipeline includes IMA402, IMA203CD8 and anzutresgene autoleucel (anzu-cel; IMA203). Anzu-cel is being evaluated in the randomized Phase 3 SUPRAME trial in patients with unresectable or metastatic melanoma whose disease progressed during or after at least one immune checkpoint inhibitor treatment. Exploratory analyses from its Phase 1b melanoma cohort, using a September 24, 2025, data cutoff, indicated durable clinical benefit after a one-time treatment. The analyses suggested that lower tumor burden, lower lactate dehydrogenase (LDH) levels and a higher effector-to-target ratio might be associated with longer progression-free survival; no single baseline characteristic was identified as a predictor of prolonged PFS. Immatics Chief Medical Officer Cedrik Britten, M.D., Ph.D., said the ESMO presentations reinforce the potential of IMA402 as an off-the-shelf treatment option and the broad development potential of IMA203CD8 in advanced PRAME-positive cancers. The company is also exploring combination strategies, including IMA402 with immune checkpoint inhibitors, IMA402 with IMA401 in lung cancer and anzu-cel with Moderna’s PRAME mRNA therapy. These approaches are intended to expand the potential applications of PRAME-directed treatments, but their benefits must be established in clinical trials. The ESMO data provide early evidence of activity in heavily pretreated populations, while the size of individual subgroups, follow-up duration and differences in trial design should be considered when interpreting the results. Further clinical development will determine whether the observed responses and durability translate into meaningful outcomes for patients across the targeted cancer types.

Source: Immatics,release