FDA Approves Tebentafusp-Tebn for Uveal Melanoma

The FDA has approved tebentafusp-tebn (Kimmtrak®, Immunocore) for the treatment of patients with HLA-A*02:01–positive unresectable or metastatic uveal melanoma.

“Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a one-year overall survival of approximately 50% in patients with metastatic uveal melanoma,” wrote Paul Nathan, MD, PhD, Consultant Medical Oncologist at the Mount Vernon Cancer Centre in the United Kingdom, and colleagues in their published results of the IMCgp100-202 clinical trial (NCT03070392), on which the approval was based. “Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100–positive cells.”

The open-label phase 3 trial enrolled 378 patients with previously untreated HLA-A*02:01–positive metastatic uveal melanoma. Patients were assigned in a 2:1 ratio to receive tebentafusp 20 mcg intravenously on Day 1, 30 mcg intravenously on Day 8, 68 mcg intravenously on Day 15, and 68 mcg intravenously once every week thereafter or investigator’s choice of treatment with single-agent pembrolizumab, ipilimumab, or dacarbazine. The primary end point was overall survival. Progression-free survival and overall response rate were secondary end points.

Tebentafusp produced a statistically significant improvement in overall survival compared with the investigator’s choice treatment arm (73% vs 59%, P<0.001). Statistical significance was also achieved in progression-free survival at six months in the tebentafusp group compared with the control group (31% vs 19%, P=0.01).

The most common adverse reactions occurring in at least 30% of patients receiving tebentafusp-tebn were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common laboratory abnormalities occurring in at least 50% of patients were decreased lymphocyte count, increased creatinine, increased glucose, increased aspartate aminotransferase, increased alanine aminotransferase, decreased hemoglobin, and decreased phosphate. The prescribing information includes a warning that patients should be monitored for cytokine release syndrome for at least 16 hours after the first infusion of tebentafusp and then as clinically indicated.

“Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma,” concluded Dr. Nathan and colleagues in their September 2021 publication of the results in The New England Journal of Medicine.

The recommended dose of tebentafusp-tebn is 20 mcg intravenously on Day 1, 30 mcg intravenously on Day 8, 68 mcg intravenously on Day 15, and 68 mcg intravenously once every following week until disease progression or unacceptable toxicity.

For More Information

Nathan P, Hassel JC, Rutkowski P, et al (2021). Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med, 385(13):1196-1206. DOI:10.1056/NEJMoa2103485

Clinicaltrials.gov (2021). Safety and efficacy of IMCgp100 versus investigator choice in advanced uveal melanoma. NLM identifier: NCT03070392.

Kimmtrak® (tebentafusp-tebn) prescribing information (2022). Immunocore. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761228s000lbl.pdf

Immunocore Holdings Limited (2022). Immunocore announces FDA approval of KIMMTRAK® (tebentafusp-tebn) for the treatment of unresectable or metastatic uveal melanoma. Available at: 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

Image credit: Nephron. Licensed under CC BY-SA 3.0

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