The Food and Drug Administration (FDA) has approved Kimmtrak® (tebentafusp-tebn) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.

Tebentafusp-tebn is a bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. The product is designed to specifically target gp100, a lineage antigen expressed in melanocytes and melanoma. In vitro, tebentafusp-tebn bound to HLA-A*02:01-positive uveal melanoma cells and activated polyclonal T cells to release inflammatory cytokines and cytolytic proteins, which resulted in direct lysis of uveal melanoma tumor cells.

The approval was based on data from the multicenter, open-label, randomized phase 2 IMCgp100-202 trial (ClinicalTrials.gov Identifier: NCT03070392), which assessed the efficacy and safety of tebentafusp-tebn in 378 HLA-A*02:01-positive adults with previously untreated metastatic uveal melanoma. Patients were randomly assigned 2:1 to receive tebentafusp-tebn administered via intravenous infusion or investigator’s choice (dacarbazine, ipilimumab, or pembrolizumab) until confirmed disease progression or unacceptable toxicity. The primary endpoint was overall survival, defined as the time from patient inclusion to date of death due to any cause up to 40 months.


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Results showed that treatment with tebentafusp-tebn was associated with a clinically and statistically meaningful overall survival benefit as a first-line treatment in the intent-to-treat population (hazard ratio [HR] 0.51; 95% CI, 0.37-0.71; P <.0001) compared with the investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine). Median progression-free survival was 3.3 months (95% CI, 3-5) in the tebentafusp-tebn arm and 2.9 months (95% CI, 2.8-3) in the investigator’s choice arm (HR 0.73; 95% CI, 0.58-0.94; P =.0139).

The most common adverse reactions reported with tebentafusp-tebn were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache and vomiting. Decreased lymphocyte count, increased creatinine, increased glucose, increased aspartate aminotransferase, increased alanine aminotransferase, decreased hemoglobin, and decreased phosphate were the most common laboratory abnormalities.

Kimmtrak carries a Boxed Warning associated with a risk of cytokine release syndrome, which may be serious or life-threatening. Patients treated with Kimmtrak should be monitored for at least 16 hours following the first 3 infusions and then as clinically indicated.

Kimmtrak is supplied as 100mcg/0.5mL of tebentafusp-tebn in a single-dose vial. The product is expected to be available in the coming weeks.

References

  1. Immunocore announces FDA approval of Kimmtrak® (tebentafusp-tebn) for the treatment of unresectable or metastatic uveal melanoma. News release. Immunocore Holdings Limited. Accessed January 26, 2022. https://www.globenewswire.com/news-release/2022/01/26/2373344/0/en/Immunocore-announces-FDA-approval-of-KIMMTRAK-tebentafusp-tebn-for-the-treatment-of-unresectable-or-metastatic-uveal-melanoma.html
  2. Kimmtrak. Package insert. Immunocore Holdings Limited; 2021. Accessed January 26, 2022. https://ir.immunocore.com/static-files/4e58e85c-de58-4b36-8076-f14cf1cbe206

This article originally appeared on MPR