Phase 3 Study Shows Statistically Significant Survival With Tebentafusp in Metastatic Uveal Melanoma

Overall survival (OS) was statistically significantly improved with tebentafusp compared with investigator’s choice of therapy as treatment of patients with metastatic uveal melanoma in the phase 3 IMCgp100-202 study (NCT03070392), Immunocore announced in a press release.

The novel bispecific protein is made of a soluble T-cell receptor that is fused to an anti-CD3 immune-effector function, and it targets gp100 specifically, an antigen expressed in melanocytes and melanoma.

Tebentafusp is the first agent coming out of the ImmTAC technology platform at Immunocore that is designed to redirect and activate T-cells to identify and kill tumor cells. Tebentafusp also received prior Fast Track and Orphan Drug designations from the FDA, as well as Promising Innovative Medicine designation under the UK Early Access to Medicines Scheme.

“To our knowledge, this is the first survival benefit for any TCR therapeutic and for any bispecific in a solid tumor,” stated David Berman, head of Research and Development, Immunocore. “The survival benefit observed in a randomized trial against checkpoint inhibitors validates our ImmTAC platform as we expand to study other cancers with high unmet need. Uveal melanoma has one of the lowest tumor mutational burdens (TMB) and these results suggest our ImmTAC platform should be evaluated in tumors with low or high TMB status.”

The study evaluated OS as the primary end point among patients with previously untreated metastatic uveal melanoma, in which 378 patients were split 2:1 to receive the study drug or investigator’s choice, which included either dacarbazine, ipilimumab (Yervoy), or pembrolizumab (Keytruda).

Overall, the OS hazard ratio for tebentafusp over the other agents was 0.51 in the intention-to-treat population, and Kaplan-Meier analysis data, although not yet mature, estimate a 1-year OS rate of 73% for the study drug versus 58% with investigator’s choice. These data confirm the benefit in OS observed in the phase 2 IMCgp100-102 clinical trial.

“A positive survival benefit for tebentafusp represents a major step towards bringing a potential new treatment for cancer patients with a high unmet need,” said Bahija Jallal, chief executive officer, Immunocore, in a statement. “If approved, tebentafusp would be the first new therapy to improve overall survival in 40 years and to be specifically indicated for metastatic uveal melanoma, a disease with poor survival and where new therapies are urgently needed. We look forward to sharing these data with the medical community and Health Authorities in the near future.”

Secondary end points included safety, objective response rate, duration of response, progression-free survival, and disease control rate, as well as some quality of life and pharmacokinetic end points.

To be included in the trial, patients had to be at least 18 years or older and have histologically or cytologically confirmed metastatic uveal melanoma. Patients had to have no prior systemic therapy in the metastatic/advanced setting, such as chemotherapy, immunotherapy, or targeted therapy; no prior regional, liver-directed therapy including chemotherapy, radiotherapy, or embolization; a life expectancy of at least 3 months; and an ECOG performance status of 0 or 1 at screening. Patients were allowed to receive prior surgical resection for oligometastatic disease, as well as neoadjuvant or adjuvant therapy of curative intent.

Patients were excluded from the study if they had any out-of-range laboratory values, a history of severe hypersensitivity reactions to other biologic drugs or monoclonal antibodies, clinically significant cardiac or impaired cardiac function, or the presence of symptomatic or untreated central nervous system metastases.

Uveal melanoma is known to be a rare and aggressive type of melanoma, and it primarily affects the eye. Patients with uveal melanoma typically have poor prognosis, and there are currently no accepted optimal management approaches for these patients.

_Reference

_{Immunocore’s tebentafusp successfully activates t cells against uveal melanoma. News Release. Immunocore. November 23, 2020. Accessed November 24, 2020. https://bit.ly/371nfSZ}