The Lynx Group

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

April 2022, Vol 13, No 2

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 adult patients with HLA-A*02:01 unresectable or metastatic uveal (intraocular) melanoma. The FDA granted tebentafusp breakthrough therapy and orphan drug designations for this indication.

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 in a 2:1 ratio to tebentafusp (N = 252) or to the investigator’s choice (N = 126) of either pembrolizumab (Keytruda), ipilimumab (Yervoy), or dacarbazine. Tebentafusp was administered weekly by intravenous 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 in the trial was overall survival. An additional efficacy outcome was investigator-assessed progression-free survival per RECIST version 1.1.

The median overall survival 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, 0.51; 95% CI, 0.37- 0.71; P <.0001). The progression-free survival was 3.3 months (95% CI, 3-5) with tebentafusp and 2.9 months (95% CI, 2.8-3) with the investigator’s choice (hazard ratio, 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.

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