November 23, 2020 - Tebentafusp showed superiority in overall survival compared with investigator’s choice of therapy in patients with previously untreated metastatic uveal melanoma.
Tebentafusp (IMCgp100) showed superiority in overall survival (OS) compared with investigator’s choice of therapy in patients with previously untreated metastatic uveal melanoma, according to results of a preplanned interim analysis of the phase 3 IMCgp100-202 trial (NCT03070392).
Results showed that tebentafusp led to a 49% reduction in the risk of death compared with standard therapy, which consisted of pembrolizumab (Keytruda; 82%), ipilimumab (Yervoy; 12%), and dacarbazine (6%; HR, 0.51; 95% CI, 0.36-0.71; P < .0001), meeting the pre-defined boundaries for statistical significance.
The analysis, which was conducted by an Independent Data Monitoring Committee, also showed that though the OS data are immature; however, the 1-year OS rates with tebentafusp and investigator’s choice of therapy were 73% and 58%, respectively.
The full findings are expected to be presented at an upcoming medical meeting, and will also be submitted for publication in a peer-reviewed journal, according to Immunocore, the developer of tebentafusp. This is the first positive clinical trial for a T-cell receptor therapeutic, and the first for any bispecific, in a solid tumor, the company added.
“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 of Immunocore. “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.”
These data confirm the phase 2 findings of the IMCgp100-102 in patients with previously treated metastatic uveal melanoma, which will be presented at the 2020 ESMO Immuno-Oncology Virtual Congress in December.
Tebentafusp is a novel bispecific protein comprised of a soluble T cell receptor that is fused to an anti-CD3 immune-effector domain. It is also engineered to target gp100, which is a lineage antigen expressed in melanocytes and melanoma. Previously, tebentafusp was granted fast track designation and orphan drug designation by the FDA, along with a Promising Innovative Medicine designation under UK Early Access to Medicines Scheme.
In the phase 3 IMCgp100-202 trial, investigators are evaluating the survival of tebentafusp compared with investigator’s choice (either dacarbazine, ipilimumab, or pembrolizumab) in patients with previously untreated uveal melanoma. A total 378 patients were randomized 2:1 to either investigator’s choice of therapy at their standard dosing schedules, tebentafusp at 20 mcg on cycle 1 of day 1, followed by 30 mcg on cycle 1 of day 8, and then 68 mcg on cycle 1 of day 15, and weekly thereafter by intravenous infusion over 15 minutes, until disease progression or unacceptable toxicity.
To be eligible for enrollment, patients could not have received prior systemic or liver-directed chemotherapy, radiation, or immunotherapy in the advanced setting. Additionally, patients must have been at least 18 years old, have histologically or cytologically confirmed metastatic uveal melanoma, be HLA A*0201 positive by central assay, have an ECOG performance status of 0 or 1, and have measurable or non-measurable disease according to RECIST v1.1 criteria.
The primary end point is OS; key secondary outcome measures are progression-free survival, objective response rate, duration of response, and disease control rate.
“To our knowledge, this is the first survival benefit for any TCR therapeutic and for any bispecific in a solid tumor. 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,” David Berman, head of Research and Development, Immunocore, said. “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.”
Immunocore’s tebentafusp demonstrates superior overall survival compared to investigator’s choice in a phase 3 clinical trial of patients with previously untreated metastatic uveal melanoma. News release. Immunocore. November 23, 2020. Accessed November 23, 2020. https://bit.ly/33akuO0.