On 25 January 2022, the US Food and Drug Administration (FDA) approved tebentafusp-tebn (Kimmtrak, Immunocore Limited), a bispecific gp100 peptide-HLA-directed CD3 T cell engager, for HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.

Efficacy was evaluated in IMCgp100-202 (NCT03070392), a randomised, open-label, multicentre study of 378 patients with metastatic uveal melanoma. Patients were required to be HLA-A*02:01 genotype positive identified by a central assay. Patients were excluded if prior systemic therapy or localised liver-directed therapy were administered. Prior surgical resection of oligometastatic disease was permitted. Patients with clinically significant cardiac disease or symptomatic, untreated brain metastases were excluded.

Patients were randomised (2:1) to receive tebentafusp-tebn (N=252) or investigator’s choice (N=126) of either pembrolizumab, ipilimumab, or dacarbazine. Tebentafusp-tebn 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 toxicity. The main efficacy outcome measure was overall survival (OS). An additional efficacy outcome was investigator-assessed progression-free survival (PFS) per RECIST v1.1.

Median OS was 21.7 months (95% confidence interval [CI] 18.6, 28.6) for patients treated with tebentafusp-tebn and 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 < 0.0001). PFS was 3.3 months (95% CI 3, 5) for those receiving tebentafusp-tebn 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 = 0.0139).

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

The recommended tebentafusp-tebn dose administered intravenously is: 

  • 20 mcg on day 1,
  • 30 mcg on day 8,
  • 68 mcg on day 15, and
  • 68 mcg once weekly thereafter.

Full prescribing information for Kimmtrak is available here.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and the United Kingdom’s Medicines and Healthcare product Regulatory Agency. The application reviews may be ongoing at the other regulatory agencies.

This review used the Real-Time Oncology Review pilot programme, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review, breakthrough designation and orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate