Results from an open-label Phase III study show that UK biotech Immunocore’s T-cell receptor therapy tebentafusp significantly improved overall survival of patients with metastatic uveal melanoma versus standard treatment.
T-cell receptor (TCR) therapies are a new class of immunotherapy that “use an engineered high-affinity T-cell receptor to target any protein, including intracellular antigens, that is presented as a peptide–HLA complex on the target-cell surface,” explain the researchers in a NEJM paper describing their research. They are primarily being developed to treat cancer, autoimmune diseases, and infections.
So far, no TCR therapies have yet been approved for use in patients, although many are under development. Immunocore is ahead of the game with tebentafusp, which already has priority review status with the FDA and is under accelerated review with the EMA. These positive Phase III data should go some way towards achieving market approval for the Oxfordshire-based company’s candidate.
Uveal melanoma, a hard-to-treat cancer that affects the eye, makes up around 3-5% of all melanomas. As many as half of these patients develop metastases, often in the liver, and their prognosis is very poor with a median survival of approximately 1 year.
According to the study, tebentafusp is the first systemic therapy that shows a survival benefit for patients with this type of cancer. It is a bispecific protein made up of a TCR bound to an “anti-CD3 single-chain variable fragment–activating domain.”
The study enrolled 378 patients with previously untreated HLA-A*02:01–positive metastatic uveal melanoma to receive either tebentafusp or the investigators choice of single-agent pembrolizumab, ipilimumab, or dacarbazine (control group) in a 2:1 ratio.
Overall survival at 1 year was 73% in patients treated with tebentafusp and 59% in the control group, reducing the risk for death during this time by 49%. Progression-free survival also improved with tebentafusp versus controls and was seen in 31% and 19% of the two groups, respectively, after 6 months.
Cytokine mediated and skin-related adverse events were the most common side effects reported with tebentafusp, but these decreased after 3-4 doses and only led to discontinuation of treatment in 2% of the participants.
“The publication of these Phase III data… demonstrates the significance of Immunocore’s work in the field of TCR therapy,” said Bahija Jallal, CEO of Immunocore.
“This further validates the potential of tebentafusp to provide a much needed treatment option for patients with metastatic uveal melanoma, making a meaningful difference to patients’ lives. In addition, we believe these data show the broader potential of Immunocore’s TCR technology for the treatment of other solid tumors.”
Tebentafusp is the company’s lead candidate, but it also has several others at earlier stages of development that are being designed to target solid tumors such as those seen in gastric, head and neck, lung, and ovarian cancer.