The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended granting a marketing authorisation for tebentafusp (Kimmtrak; Immunocore), a novel immunotherapy agent for the first-line treatment of uveal melanoma.
The recommendation by the CHMP comes just a month after the drug's approval by the US Food and Drug Administration.
Dr Bahija Jallal, chief executive officer of Immunocore, said: "The CHMP’s recommendation of Kimmtrak brings us closer to providing a much-needed treatment option to patients in Europe."
Uveal melanoma is a rare form of intraocular malignancy in adults. Its presentation is very aggressive and around half of the affected individuals are likely to develop metastatic disease.
Dr Paul Nathan, uveal melanoma lead for the European Organisation for Research and Treatment of Cancer, said: "Metastatic uveal melanoma has historically been associated with a particularly poor prognosis and, up until now, has been refractory to most treatments. Kimmtrak represents a significant new form of treatment, offering the chance at a longer life for patients with the disease, and with it, hope."
Tebentafusp is a novel bispecific protein comprising a soluble T-cell receptor fused to an anti-CD3 immune-effector function, the first in the class of T-cell receptor bispecific immunotherapies. The drug is only applicable for use in patients of HLA-A*02:01 genotype as the T-cell receptor binding domain specifically recognizes a gp100-derived peptide on HLA-A*02:01.
Efficacy and Safety Data
The CHMP's recommendation is based on data from a randomised phase 3 pivotal trial (IMCgp100-202) published last September in the New England Journal of Medicine. The study involved 378 previously-untreated patients with metastatic uveal melanoma of the genotype HLA-A*02:01. The participants were randomly assigned to receive either tebentafusp (n=252) or investigator's choice of therapy (n=126) which included pembrolizumab, ipilimumab, or dacarbazine.
In the intent-to-treat population, there was a significant overall survival benefit in favour of tebentafusp over investigator's choice (21.7 vs. 16.0 months; HR 0.51; 95% CI 0.37 to 0.71; P<0.0001). The tebentafusp arm also demonstrated improved progression-free survival compared with the investigator's choice arm (3.3 vs. 2.9 months; HR 0.73; 95% CI 0.58 to 0.94; P=0.0139).
"Kimmtrak is the first therapy to demonstrate a survival benefit in patients with this disease, providing new hope to these individuals and to the doctors treating them," Dr Jallal added.
Most common side effects in the tebentafusp group were cytokine-mediated and skin-related events. Overall, treatment-related adverse events (AEs) were manageable and only 2% discontinued treatment due to the AEs. There were no treatment-related deaths in the trial. Cytokine release syndrome (CRS) of grade 3 occurred in les than 1% of participants and was generally well-managed. There were no grade 4 CRS events reported.
The CHMP's favourable opinion is an intermediate step in the drug's journey towards patient access. The European Commission will further review the decision to be adopted on a marketing authorisation across the EU.
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