Immunocore’s investigational immunotherapy tebentafusp (IMCgp100) is superior to investigator’s choice at prolonging the lives of adults newly diagnosed with metastatic uveal melanoma — a common and hard-to-treat form of eye cancer, interim data from a Phase 3 trial show.
These preliminary findings add to the positive survival benefits reported with tebentafusp’s use in a Phase 2 trial of people previously treated for this cancer, supporting the therapy’s potential in this patient population.
“A positive survival benefit for tebentafusp represents a major step towards bringing a potential new treatment for cancer patients with a high unmet need,” Bahija Jallal, Immunocore’s CEO, said in a press release.
“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,” Jallal added. “We look forward to sharing these data … in the near future.”
Tebentafusp is a bispecific antibody comprising a part designed to specifically target gp100, a protein highly present in melanoma cells, and another part that binds to CD3, a protein receptor found on the surface of immune T-cells.
As such, the therapy is thought to bring cancer and immune cells together, redirecting T-cell responses against cancer cells and promoting their death. It is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect T-cells to recognize and kill cancer cells.
The U.S. Food and Drug Administration granted tebentafusp orphan drug and fast track designations to treat uveal melanoma. Both programs are meant to accelerate the therapy’s clinical development and review.
Tebentafusp also received promising innovative medicine designation by the U.K.’s Medicines and Healthcare products Regulatory Agency for the same disease, meaning it is a potential candidate for a program that gives patients early access to promising therapies before their approval.
A previous Phase 1/2 trial (NCT01211262) showed that tebentafusp safely and effectively promoted anti-cancer immune responses in people with metastatic melanoma, including in those with uveal melanoma.
The international IMCgp100-202 Phase 3 trial (NCT03070392) opened to confirm tebentafusp’s safety and effectiveness in a larger group of patients with metastatic uveal melanoma.
A total of 378 participants were randomly assigned to either first-line tebentafusp or investigator’s choice of treatment: dacarbazine, Yervoy (ipilimumab), or Keytruda (pembrolizumab).
Of note, dacarbazine is a chemotherapy, while Yervoy and Keytruda are immune checkpoint inhibitors, meaning they work by targeting mechanisms used by cancer cells to evade immune attacks.
All treatments were administered directly into the bloodstream — tebentafusp every week, and the others every three weeks — until disease progression or unacceptable toxicity. Yervoy was an exception, given in four doses only.
The study’s main goal is to assess whether tebentafusp was superior to investigator’s choice at extending patients’ lives. Secondary goals include the proportion of people responding to treatment, response duration, the time patients lived without signs of disease progression, quality of life, and safety measures.
Conducted by an independent data monitoring committee, the first pre-planned interim analysis found that the trial met its main goal, with tebentafusp-treated patients showing a 49% lower risk of death than those given other therapies.
Preliminary data also suggest a superior one-year survival rate among patients in the tebentafusp group compared with those on other treatments (73% vs. 58%).
Among patients assigned investigator’s choice of treatment, Keytruda was the most common choice (82%), followed by Yervoy (12%) and dacarbazine (6%).
“To our knowledge, this is the first survival benefit for any [T-cell receptor] therapeutic and for any bispecific [antibody] in a solid tumor” reported in Phase 3 studies, said David Berman, head of Immunocore’s research and development.
“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,” he added.
IMCgp100-202’s final results are expected to be presented at an upcoming scientific conference, and to be submitted for publication in a peer-reviewed journal.
Promising survival benefits were also observed with tebentafusp in the IMCgp100-102 Phase 2 study (NCT02570308), which involved 127 uveal melanoma patients whose disease progressed after at least one therapy.
Results showed that 62% of patients were alive after one year of tebentafusp treatment, an improvement from the 40% historical survival rate in this patient population. Even greater one-year survival rates (between 77% and 86%) were observed among patients showing signs of target immune responses.
Tebentafusp-related adverse events were generally predictable and manageable, reducing in frequency and severity after the first three doses. Less than 4% of trial participants discontinued treatment due to adverse events, and there were no reports of fatal treatment-related events.
