Immunocore doubles up on T-cell engagers in eye cancer

Why it matters: The early result exceeds the 45% two-year survival seen with Kimmtrak alone in its landmark Phase 3 trial, raising the possibility that attacking two tumor targets could improve on the existing treatment for this rare and aggressive eye cancer.

“These encouraging Phase 1 data suggest combining brenetafusp with tebentafusp may offer a meaningful new option for HLA-A*02:01-positive patients with metastatic uveal melanoma,” said Mohammed Dar, Immunocore’s chief medical officer, in a press release.

Zoom in: At the June data cutoff, 26 patients had received both drugs; the efficacy results highlighted 17 evaluable first-line patients. The combination shrank tumors in 29% and controlled disease in 71%, with median progression-free survival of 8.1 months and a median response duration of 24.1 months.

Median overall survival had not been reached after a median 29 months of follow-up, and 10 of the 17 patients remained on study. Seven of the 11 patients alive beyond two years had received no other anti-cancer treatment.

Among all 26 combination-treated patients, 77% experienced cytokine release syndrome, an inflammatory response to immune activation, and 38% had Grade 3 or 4 treatment-related adverse events. No treatment-related discontinuations or deaths were reported.

How it works: Kimmtrak, the first approved T-cell receptor therapy, was also developed by Immunocore, a spinout of Germany’s Medigene. It uses an engineered T-cell receptor to recognize the gp100 melanoma protein, while brenetafusp targets another tumor-associated protein, PRAME. Both recruit immune cells through CD3, and Immunocore hopes the dual approach will attack cancer cells that express one or both targets.

Reality check: The SITC presentation compares the small, 17-patient cohort with the 252 patients who received Kimmtrak alone in an earlier Phase 3 trial, rather than a randomized control group within the new study. Differences in baseline risk factors, including disease burden, as well as patient selection and subsequent therapies could account for some of the apparent survival advantage.

Immunocore told European Biotechnology that the 95% confidence interval for median overall survival starts at 18.5 months, with an upper limit that cannot yet be calculated. That range includes the 21.6-month median reported for Kimmtrak alone in the earlier trial.

The median progression-free survival estimate also had a wide 95% confidence interval of 1.9 to 30.4 months. In exploratory testing, eight of nine evaluable patients had reductions in circulating tumor DNA, including clearance in four, but the molecular findings remain preliminary.

The competition: U.S. developer IDEAYA Biosciences, which licensed rights to darovasertib outside the U.S. to France’s Servier, submitted an FDA application for darovasertib plus crizotinib in metastatic uveal melanoma. The combination does not require the HLA-A*02:01 genetic marker needed for Kimmtrak.

Follow the money: Immunocore’s third-quarter results put Kimmtrak net sales at $102.2 million (€91.5 million), including $34.9 million (€31.3 million) in Europe, down slightly from $103.7 million (€92.9 million) worldwide a year earlier. Nine-month sales rose 10% to $324.8 million (€290.9 million).

The company attributed the quarterly comparison to U.S. inventory timing and an extra sales week in 2025, estimating underlying growth of about 10%. It held $901.3 million (€807.3 million) in cash, cash equivalents and marketable securities at the end of September.

Immunocore’s shares rose 9.1% on Friday, closing at $30.99 (€27.76) on Nasdaq.

What’s next: Immunocore plans to start DUET-UVEAL, a randomized Phase 2/3 trial of the combination in HLA-A*02:01-positive unresectable or metastatic uveal melanoma, but has not disclosed when enrollment will begin. “We are working on DUET-UVEAL at the moment,” the company told European Biotechnology. “We will start it as soon as possible, but cannot commit on exact timings.”

Immunocore has three ongoing Phase 3 trials: TEBE-AM, testing Kimmtrak in previously treated advanced cutaneous melanoma; PRISM-MEL-301, evaluating brenetafusp with nivolumab in first-line advanced cutaneous melanoma; and the EORTC-sponsored ATOM trial of tebentafusp as adjuvant treatment for uveal melanoma. TEBE-AM has completed enrollment, with topline overall survival results expected in the second quarter of 2027.

Bottom line: The combination could build on Kimmtrak while Immunocore pursues a broader melanoma pipeline, but demonstrating an additional survival benefit in a randomized trial will be crucial.