Tebentafusp Granted FDA Breakthrough Therapy Designation for Unresectable or Metastatic Uveal Melanoma

The FDA has granted a Breakthrough Therapy Designation to tebentafusp for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma .

The FDA has granted a Breakthrough Therapy Designation (BTD) to tebentafusp (IMCgp100) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM), according to a press release from Immunocore.

“We are delighted that the FDA has granted Breakthrough Therapy Designation for tebentafusp based on the survival benefit from our Phase 3 clinical trial announced in November 2020. There is an urgent need for an approved treatment for this rare and aggressive form of melanoma and we look forward to continuing to work with regulators to bring tebentafusp to patients as quickly as possible,” said Bahija Jallal, CEO, Immunocore, in a statement.

In the ongoing phase 3 randomized, open-label, multi-center IMCgp100-202 study (NCT03070392), tebentafusp is being compared with investigator’s choice of either dacarbazine, ipilimumab (Yervoy), or pembrolizumab (Keytruda) in patients with advanced uveal melanoma. Findings from the pre-planned interim analysis showed that the study achieved its primary end point of overall survival (OS) in the intent-to-treat population with a hazard ratio (HR) of 0.51 (95% CI, 0.36-0.71; <.0001), favoring tebentafusp. According to earlier data, tebentafusp led to a 1-year OS rate of 73%, which has been improved upon with longer follow-up, compared with 58% with investigator’s choice.

In the study, tebentafusp is dosed at 20 mcg on day 1 cycle 1, followed by 30 mcg on day 8 of cycle 1, then 68 mcg on day 15 in cycle 1, and on a weekly basis thereafter via intravenous (IV) infusion over 15 minutes. Patients for whom the investigator chooses dacarbazine receive the drug at 1000 mg/m2 of body surface area by IV infusion every 3 weeks. Treatment with ipilimumab is administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks, and pembrolizumab is administered at 2 mg/kg IV infusion over 30 minutes every 3 weeks. All study treatments are continued until confirmed disease progression or unacceptable toxicity.

Aside from OS, the study explored secondary end points of safety, objective response rate, duration of response, disease control rate, progression-free survival, quality of life, and pharmacokinetics.

Trial enrollment has been completed. To be eligible, patients were required to have histologically or cytologically confirmed metastatic uveal melanoma, be HLA A*0201 positive by central assay, have a life expectancy of at least 3 months, an ECOG performance status of 0 or 1, and have measurable or non-measurable disease according to RECIST v1.1 criteria. In terms of prior treatment, patients could not have received systemic therapy in the metastatic or advanced setting or prior regional, liver-directed therapy, but prior surgical resection of oligometastatic disease was allowed. Receipt of neoadjuvant or adjuvant therapy administered in the curative setting in patients with localized disease was also allowed.

With a BTD, the development of tebentafusp in the unresectable or metastatic uveal melanoma space will be expedited and the developer of the agent, Immunocore, will work with the FDA to facilitate submission of a future biologics license application for the agent in this setting. Tebentafusp was previously granted Fast Track Designation and Orphan Drug Designation by the FDA for the treatment of uveal melanoma, as well as a Promising Innovative Medicine Designation in the United Kingdom. Immunocore predicts that tebentafusp will become the first FDA-approved therapy for metastatic uveal melanoma in 40 years.


Immunocore’s tebentafusp granted Breakthrough Therapy Designation for unresectable or metastatic uveal melanoma from FDA. News release. Immunocore. February 19, 2021. Accessed February 19. 2021. https://bit.ly/3s1rqXM

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