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Published: Nov 23, 2020 By Mark Terry in BIOSPACE

Immunocore, based in Oxfordshire, England, Conshohocken, Pennsylvania and Rockville, Maryland, announced that its Phase III IMCgp100-202 trial of tebentafusp compared to investigator’s choice for metastatic uveal melanoma (mUM) hit the statistical significant for overall survival (OS) in its first pre-planned interim analysis.

Tebentafusp is a novel bispecific protein made up of a soluble T-cell receptor fused to an anti-CD3 immune-effector function. The drug specifically targets gp100, an antigen expressed in melanocytes and melanoma. It is the first drug coming out of Immunocore’s ImmTAC technology platform that is designed to redirect and activate T-cells to identify and kill tumor cells.

The drug received Fast Track Designation and orphan drug designation by the U.S. Food and Drug Administration (FDA) and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme.

Uveal melanoma is a rare and aggressive form of melanoma. It primarily affects the eye. There are no currently accepted optimal management regimens or treatments. The prognosis is typically poor.

The trial evaluated the OS of tebentafusp compared to an investigator’s choice of either dacarbazine, ipilimumab or pembrolizumab in patients with previously untreated mUM. In the trial, 378 patients were split 2:1 to receive either tebentafusp or investigator’s choice.

“To our knowledge, this is the first survival benefit for any TCR therapeutic and for any bispecific in a solid tumor,” said David Berman, Head of R&D for 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.”

Tebentafusp edged out the other drugs with an OS Hazard Ratio of 0.51 in the intent-to-treat population. Although the data isn’t mature, the Kaplan-Meier analysis estimates a one-year OS rate of about 73% compared to 58% (for the other choices). The efficacy data confirms the OS results seen in the Phase II IMCgp100-102 treat in previously treated mUM.

“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, Immunocore’s chief executive officer. “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.”

Immunocore’s focus is on developing a novel class of TCR bispecific immunotherapies, ImmTAX—Immune mobilizing monoclonal TCRs Against X disease. The hope is they can be designed to treat a range of diseases, including cancer, infectious diseases and autoimmune disorders. It is using the ImmTRAX platform to develop a deep pipeline across multiple therapeutic areas, including five clinical stage programs in oncology and infectious disease, and advanced preclinical programs in autoimmune disease and multiple earlier-preclinical programs. Tebentafusp is its most advanced oncology candidate.

The company has partnerships with Genentech, GlaxoSmithKline, AstraZeneca, Eli Lilly and the Bill and Melinda Gates Foundation.