Immatics shows off its PRAME bispecific data at ESMO 2026
Germany-based cancer immunotherapy specialist Immatics presented updated clinical data for two PRAME-targeted drug candidates at the ESMO Congress 2026 in Madrid. Particularly striking is the survival signal for the bispecific T-cell engager IMA402: In a subgroup of patients with advanced melanoma and high PRAME expression, 91% were still alive after one year. Median overall survival had not yet been reached at the time of analysis.
This is an encouraging signal, but it does not yet prove that IMA402 extends patients’ lives. The data come from an ongoing Phase 1b study without a control group. Moreover, follow-up for overall survival was still relatively short, at a median of 8.8 months. The one-year rate is therefore an early estimate, rather than a comparison with an established therapy.
IMA402: As of the June 1, 2026, cutoff date, 126 patients with various advanced solid tumors had received at least one infusion of IMA402. They had previously received a median of three lines of systemic therapy. The efficacy analysis for the recommended Phase 2 dose range included 40 patients, 31 of whom had high PRAME expression, a cancer-associated protein that helps T cells identify tumors when targeted by treatment.
In this analysis group, IMA402 achieved a confirmed objective response rate of 25%: Tumors shrank measurably according to the study criteria in 10 of 40 patients. The disease control rate was 63%. In the subgroup with high PRAME expression, the confirmed response rate was 32%. Among the 22 melanoma patients in this group, seven responded to treatment. Median duration of response was 12.5 months; the longest ongoing remission had lasted more than two years.
The survival data also relate to the melanoma group with high PRAME expression. According to Immatics, 91% of patients were still alive after one year. For comparison, the company cites a one-year survival rate of 60% in patients treated below the recommended dose range. This difference is interesting, but it cannot readily be interpreted as a dose effect or an efficacy advantage: The dose groups were not compared in a randomized setting and may also differ in other characteristics. The small number of patients is a further limitation.
The response rate also needs to be put into context: 32% means that seven of 22 patients had a confirmed objective response — not that one-third of patients were cured. The duration of response provides an additional indication of potential clinical relevance, but it likewise cannot replace controlled evidence of efficacy.
A T-cell engager targeting a tumor antigen: IMA402 is part of Immatics’ TCER platform. The bispecific drug recognizes a peptide derived from the tumor antigen PRAME that is presented on the cell surface by the HLA molecule HLA-A*02:01, while simultaneously binding to CD3 on T cells. This is intended to enable the immune cells to recognize and attack tumor cells. Its use requires tumor cells to present the appropriate peptide-HLA complex; PRAME expression alone is not necessarily sufficient.
Immatics describes the tolerability profile as favorable. The most common treatment-related adverse events included transient lymphopenia and low-grade cytokine release syndrome. According to the company, no cases of immune effector cell-associated neurotoxicity syndrome (ICANS) and no treatment-related deaths were observed. However, the limited number of patients treated so far does not yet allow a definitive assessment of rare or late-onset risks.
Immatics plans to investigate IMA402 in additional solid tumors and in combination with immune checkpoint inhibitors. Initial data for a combination with the MAGEA4/8-targeted bispecific IMA401 in lung cancer are expected in 2027. The company is also relying on its own blood-based test to select patients with high PRAME expression.
PRAME-targeted cell therapy: Alongside IMA402, Immatics presented data for IMA203CD8, a personalized TCR T-cell therapy. In this approach, patients’ T cells are genetically modified to recognize PRAME-derived peptides and then reinfused. The therapy thus differs fundamentally from the bispecific antibody, which activates T cells already present in the body.
As of the Aug. 7, 2026, data cutoff, a total of 98 heavily pretreated patients had been enrolled in the ongoing Phase 1 study; 90 were evaluable for efficacy. Across all dose levels and tumor types studied, the confirmed response rate was 41%. This overall figure also includes lower doses that were not selected for further clinical development.
In a more narrowly defined group of 20 patients with gynecologic tumors who had received clinically relevant doses, the confirmed response rate was 55%. Median duration of response was 8.4 months. Median progression-free survival was 5.8 months; median overall survival had not yet been reached at a median follow-up of 7.8 months. Given the small, nonrandomized Phase 1 population, these results should also be viewed as early clinical signals at this stage.
