FDA Approves Immunocore’s Kimmtrak to Treat Unresectable or Metastatic Uveal Melanoma
January 26, 2022
The U.S. Food and Drug Administration approved Immunocore’s T cell receptor bispecific immunotherapy Kimmtrak for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.
Kimmtrak is the first TCR therapeutic to receive regulatory approval from the FDA, the first bispecific T cell engager to receive regulatory approval from the FDA to treat a solid tumor, and the first and only therapy for the treatment of unresectable or metastatic uveal melanoma to be approved by the FDA.
Uveal melanoma is a rare and aggressive form of melanoma, which affects the eye. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, and up to 50 percent of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma (mUM) typically has a poor prognosis and had no approved treatment until Kimmtrak.
“Every year in the United States, hundreds of people are diagnosed with metastatic uveal melanoma who, until now, had no approved treatment options,” said Bahija Jallal, CEO of Immunocore. “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.
He noted that the approval validates the strength of the company’s platform and opens doors to explore further breakthrough discoveries in TCR therapeutics for the treatment of other cancers and diseases with high unmet need.
“Uveal melanoma is a devastating disease that has historically resulted in death within a year of metastasis for our patients,” said 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.”
Kimmtrak is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. Kimmtrak specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognize and kill tumor cells. Kimmtrak has been granted Breakthrough Therapy, Fast Track, and Orphan Drug designations by the FDA in the United States, Accelerated Assessment by the EMA, and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma.
The approval is based on the results of Immunocore’s phase 3 IMCgp100-202 clinical trial, which were published in the New England Journal of Medicine in September 2021. The randomized pivotal trial evaluated overall survival (OS) of Kimmtrak compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in patients with previously untreated mUM. Some 378 patients were randomized in a 2:1 ratio to either Kimmtrak or investigator’s choice. Data from the trial, the largest phase 3 trial undertaken in mUM, showed that Kimmtrak demonstrated unprecedented median OS benefit as a first-line treatment. The OS Hazard Ratio (HR) in the intent-to-treat population favored Kimmtrak, had a hazard ratio of 0.51, over investigator’s choice (82 percent pembrolizumab; 13 percent ipilimumab; 6 percent dacarbazine) and a median OS of almost 22 months. In the clinical trials, across both arms, patients stopped treatment for disease progression, unless the patient was otherwise deriving benefit, or for unacceptable toxicity.
Treatment-related adverse reactions were manageable and consistent with the proposed mechanism. Among the patients treated with Kimmtrak, the most common Grade 3 or higher adverse reactions were rash (18 percent), pyrexia (4 percent), and pruritus (5 percent). In the 245 patients treated with Kimmtrak, Grade 3 cytokine release syndrome (CRS) occurred in less than 1 percent of patients and were generally well-managed. There were no Grade 4 or fatal CRS events observed in the Phase 3 trial. A boxed warning is included for CRS as it has the potential to become serious or life-threatening if not managed appropriately.
Immunocore is ready to commercialize Kimmtrak and expects to make the product commercially available in the United States within weeks and has set up a program to help patients obtain access.
The European Medicines Agency (EMA), the United Kingdom’s Medicines and Healthcare Regulatory Agency (MHRA), Health Canada, and the Australian Government Department of Health Therapeutic Goods Administration (TGA) have accepted the submission of the company’s Marketing Authorization Application. Additionally, Immunocore launched a global early access program to make Kimmtrak readily available to mUM patients.
Author: Rare Daily Staff
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