The FDA approved Kimmtrak for the treatment of HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma (mUM).
The U.S. Food and Drug Administration approved Immunocore’s Kimmtrak (tebentafusp-tebn) for treatment of HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma (mUM).
Uveal melanoma is an aggressive and rare type of melanoma that affects the eye. Up to half of people with uveal melanoma will eventually develop metastatic disease. When it is unresectable or metastatic, it typically has a poor prognosis. There have been no approved treatments until now.
The drug is a bispecific protein composed of a solute T cell receptor fused to an anti-CD3 immune-effector function. It targets gp100, a lineage antigen expressed in melanocytes and melanoma. Kimmtrak has received Breakthrough Therapy Designation, Fast Track designation and orphan drug designation by the FDA, Accelerated Assessment by the European Medicines Agency (EMA), and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme.
“Today’s approval of Kimmtrak is a historic milestone and the culmination of years of dedication by the Immunore team, patients, and our healthcare partners,” said Bahija Jallal, Chief Executive Officer of Immunocore. “Every year in the United States, hundreds of people are diagnosed with metastatic uveal melanoma who, until now, had no approved treatment options. Kimmtrak is the first therapy to demonstrate a survival benefit to patients with this disease, and we are focused on making Kimmtrak available as quickly as possible.”
The approval was built on the company’s Phase III IMCgp100-202 trial data. The study evaluated overall survival (OS) of the drug compared to investigator’s choice of either Merck’s Keytruda (pembrolizumab), Bristol Myers Squibb’s Yervoy (ipilimumab), both checkpoint inhibitors, or dacarbazine, a chemotherapeutic agent.
The patients had previously untreated mUM; 378 were randomized 2:1 to receive either Kimmtrak or investigator’s choice. The results showed the drug demonstrated “unprecedented median OS benefit as a first-line treatment” over investigator’s choice, the company said.
In the trial, treatment-related adverse reactions were manageable and consistent with what was expected with the drug’s mechanism of action. The most common Grade 3 or higher adverse reactions were rash (18%), pyrexia (4%), and pruritus (5%). Grade 3 cytokine release syndrome (CRS) was observed in less than 1% of patients and was generally well-managed. No Grade 4 or fatal CRS events were seen in the Phase III trial. Kimmtrak is approved with a boxed warning, including CRS.
“Uveal melanoma is a devastating disease that has historically resulted in death within a year of metastasis for our patients,” said Dr. John Kirkwood, Director of the Melanoma Center at the UPMC Hillman Cancer Center. “The approval of Kimmtrak represents a major paradigm shift in the treatment of metastatic uveal melanoma, and for the first time offers hope to those with this aggressive form of cancer.”
Immunocore’s focus is on developing a novel class of T cell receptor (TCR) bispecific immunotherapies. Kimmtrak is the first of their drugs to be approved.
On December 6, 2021, the company announced initial Phase I data for another of its pipeline products, IMC-C103C, a bispecific T cell engager targeting MAGE-A4 for advanced solid tumors. This drug was developed with Immunocore’s ImmTAC technology platform and in partnership with Genentech, a Roche company.
The initial trial data were from 44 patients across 10 dose-escalation cohorts. The drug showed a manageable safety profile. Most of the patients in the study had platinum relapsed/refractory ovarian cancer who were enrolled regardless of their MAGE-A4 protein expression.
Jallal, at the time, stated, “IMC-C103C is our second T cell engager to demonstrate durable clinical activity, now in multiple solid tumors. We are highly encouraged to see these responses in ovarian and head and neck cancer. The durable PRs in ovarian cancer occur in heavily pre-treated patients even with low MAGE-A4 protein tumor expression. We have initiated an expansion arm in ovarian carcinoma, while we continue signal searching and determining the optimal dose in multiple solid tumors.”
