Kimmtrak, a Bispecific CD3 T-Cell Engager, First FDA-Approved Drug for Unresectable or Metastatic Uveal Melanoma

Web Exclusives - FDA Approvals

On January 25, 2022, the FDA accelerated the approval of tebentafusp-tebn (Kimmtrak; Immunocore), a bispecific gp100 peptide-HLA–directed CD3 T-cell engager, for the treatment of adults with HLA-A*02:01 unresectable or metastatic uveal (intraocular) melanoma. The FDA granted tebentafusp breakthrough therapy and orphan drug designations for this indication.

“Today’s approval of Kimmtrak is a historic milestone,” Bahija Jallal, Immonocore’s Chief Executive Officer, said in a press release. “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.”

John Kirkwood, MD, Director of the Melanoma Center at the UPMC Hillman Cancer Center, noted in the press release, “Uveal melanoma is a devastating disease that has historically resulted in death within a year of metastasis for our patients. The approval of tebentafusp-tebn 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.”

The efficacy was evaluated in the IMCgp100-202 clinical trial, a randomized, open-label, multicenter study of 378 patients with metastatic uveal melanoma. All patients had to have the HLA-A*02:01 genotype, as detected by a central assay. Patients who had previously received systemic therapy or localized liver-directed therapy were excluded, but patients who had undergone surgical resection of oligometastatic disease were allowed to participate. Patients with cardiac disease or symptomatic, untreated brain metastases were also excluded from the study.

The patients were randomized (2:1) to tebentafusp (N = 252) or to the investigator’s choice (N = 126) of either pembrolizumab, ipilimumab, or dacarbazine. Tebentafusp was administered weekly by intravenous (IV) infusion at 20 mcg on day 1; 30 mcg on day 8; 68 mcg on day 15; and every subsequent week, until disease progression or unacceptable adverse events.

The main end point was overall survival (OS). An additional efficacy outcome was investigator-assessed progression-free survival (PFS) per RECIST version 1.1.

The median OS was 21.7 months (95% confidence interval [CI], 18.6-28.6) in patients who received tebentafusp versus 16 months (95% CI, 9.7-18.4) in the investigator’s choice arm (hazard ratio [HR], 0.51; 95% CI, 0.37-0.71; P <.0001). The PFS was 3.3 months (95% CI, 3-5) with tebentafusp and 2.9 months (95% CI, 2.8-3) with the investigator’s choice (HR, 0.73; 95% CI, 0.58-0.94; P = .0139).

The most common (≥30%) adverse reactions were cytokine-release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased aspartate aminotransferase, increased alanine aminotransferase, decreased hemoglobin, and decreased phosphate levels.

The recommended IV dose of tebentafusp is 20 mcg on day 1; 30 mcg on day 8; 68 mcg on day 15; and 68 mcg once weekly, thereafter.

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Last modified: March 8, 2022
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