FDA Grants Priority Review to Tebentafusp for Uveal Melanoma Treatment

The FDA has accepted the biologics license application for tebentafusp and granted it priority review for the treatment of adult patients with HLA-A*02:01-positive metastatic uveal melanoma.

The FDA has accepted the biologics license application (BLA) for tebentafusp (IMCgp100) and granted it priority review for the treatment of adult patients with HLA-A*02:01-positive metastatic uveal melanoma (mUM), according to a press release by Immunocore Holdings Plc.1

Tebentafusp is designed to target gp100, which is a lineage antigen expressed in both melanocytes and melanoma. It is composed of soluble a T cell receptor that is fused to an anti-CD3 immune-effector function. In February of 2021, the agent was granted a breakthrough therapy designation for unrespectable of mUM. 

The BLA is support by data from a phase 2 study (NCT03070392) that compared tebentafusp with the investigator’s choice in advanced uveal melanoma. The randomized, open label, parallel assignment study has an actual enrollment of 378 participants with an estimated completion date of March 2023. The primary end point is overall survival (OS) up to 40 months. Secondary end points include safety as defined by the number of patients with treatment emergent adverse events, duration of response (DoR), progression-free survival, disease control rate, quality of life, and pharmacokinetics.2

During the study, patients were randomized to receive tebentafusp or the investigators choice of dacarbazine, ipilimumab (Yervoy), or pembrolizumab (Keytruda).

Interim analysis presented during the virtual AACR Annual Meeting found that at a median follow-up of 14.1 months, the median OS for tebentafusp was 21.7 months (95% CI, 18.6-23.6) compared to 16 months for investigators choice (95% CI, 9.7-19.4). The 1-year OS rate in the experimental arm was 73.2% versus 58.8% in the control arm.

Any grade AEs were experienced by 99.6% of patients with grade 3/4 AEs being experienced by 45% of patients. The most common AEs reported with tebentafusp was cytokine release syndrome (CRS; 89%), pyrexia (76%), chills (47%), nausea (43%), fatigue (41%), and hypotension (38%). Of reported grade 3/4 cytokine-mediated toxicities, 4% had pyrexia, 3% had fatigue, and 3% had hypotension. Additionally, 83% of patients experienced rash, 69% reported pruritus, 39% reported dry skin, and 23% had erythema. Grade 3/4 rash was seen in 18% of patients while grade 3/4 pruritus was seen in 5% of patients.

No deaths related to the study drug were reported. Additionally, Most AEs occurred in the first few weeks of treatment and then decreased in both frequency and severity.

“There is an urgent need for an approved treatment for metastatic uveal melanoma, an aggressive form of cancer for which there are very limited treatment options. We are excited to work with the FDA and European Medicines Agency to bring tebentafusp to patients as quickly as possible,” said Bahija Jallal, chief executive officer of Immunocore, in a press release.

In order to participate in the study, patients must be at least 18 years of age or older, have histologically confirmed UM, have no systemic prior therapy in the metastatic or advanced setting, no prior regional, liver-directed therapy, HLA A*0201 positive by central assay, a life expectancy greater than 3 months, measurable disease, and an ECOG status of 0 or 1. Patients with any out of range laboratory values, clinically significant cardiac disease or impaired cardiac function, untreated central nervous system metastases, active infection requiring antibiotic therapy, a known history of HIV, or any malignant disease other than the one being treated in the study are ineligible to participate.

1.Immunocore announces that U.S. Food and Drug Administration and European Medicines Agency accept biologics license application and marketing authorization application for Tebentafusp in metastatic uveal melanoma. News release. August 24, 2021. Accessed August 25, 2021. https://bit.ly/3gzS3Qd.
2. Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma. ClinicalTrials.gov. Accessed August 25, 2021. https://bit.ly/3Bd2CAB.