Immunocore ImmTAC combo shows 70% two-year OS in uveal melanoma
Immunocore has presented Phase 1/2 data showing that combining its two ImmTAC molecules, brenetafusp and approved therapy KIMMTRAK (tebentafusp-tebn), produced a two-year overall survival rate of 70% in first-line patients with metastatic uveal melanoma (mUM). The data were shared at the 2026 Society for Immunotherapy of Cancer (SITC) Annual Meeting in a poster and oral session on 6 and 7 November.
Across 17 evaluable first-line patients treated with the combination, median overall survival had not been reached at a median follow-up of 29 months, with one-year OS at 88% and two-year OS at 70%. Ten of the 17 patients remained on study at the data cut-off. The overall response rate was 29%, the disease control rate 71%, and median duration of response 24.1 months. Notably, 64% of patients surviving beyond two years had received only the brenetafusp and tebentafusp combination, with no additional therapies.
Clinical data and safety
The safety profile was broadly consistent with what has been observed for each agent individually, and no new safety signals were identified. Cytokine release syndrome, the class effect associated with T cell engagers, was the most frequent treatment-related adverse event, occurring in 77% of combination patients, though the vast majority of cases were Grade 1 or 2. Critically, no Grade 3 or 4 CRS was recorded in the combination arm. Grade 3 or 4 treatment-related adverse events were seen in 38% of combination patients, with the most common being a transient, self-resolving lymphocyte count decrease. No treatment-related adverse event led to discontinuation or death in either cohort.
Molecular response data were also encouraging: eight of nine evaluable patients showed a ctDNA response, and four achieved ctDNA clearance, suggesting durable biological activity beyond conventional imaging endpoints.
Mohammed Dar, Executive Vice President of Clinical Development and Chief Medical Officer at Immunocore, said the results suggest the combination "may offer a meaningful new option for HLA-A*02:01-positive patients," and that targeting both gp100 and PRAME simultaneously could deliver incremental benefit over tebentafusp monotherapy alone.
Market context and next steps
Immunocore plans to initiate DUET-UVEAL, a randomised Phase 2/3 trial, to evaluate the combination formally in adults with unresectable or metastatic uveal melanoma. The company describes this as the first clinical dataset demonstrating activity and a manageable safety profile for two T cell engagers used together in a solid tumour, a claim that, if it holds, would mark a meaningful proof-of-concept for the class.
Uveal melanoma is a rare and aggressive disease with a poor prognosis at the metastatic stage. KIMMTRAK was the first approved systemic therapy for HLA-A*02:01-positive mUM and demonstrated an overall survival benefit in its registrational trial, setting the standard of care in a space that had previously lacked effective options. The competitive landscape remains narrow given the rarity of the indication and the HLA restriction, but the clinical bar is rising: data from the combination arm will now be measured against the established monotherapy survival curves.
Brenetafusp is also being evaluated in first-line cutaneous melanoma in the ongoing PRISM-MEL-301 Phase 3 trial, adding a second late-stage readout that investors will monitor for further validation of the PRAME-targeting approach. The combination data presented at SITC, while from a small Phase 1 cohort, add credibility to that broader pipeline thesis.