On January 25, 2022, tebentafusp-tebn, a bispecific gp100 peptide-HLA–directed CD3 T-cell engager, was approved for treatment of adults with HLA-A*02:01–positive, unresectable or metastatic uveal melanoma.¹

Supporting Efficacy Data

Approval was based on findings in the open-label, multicenter IMCgp100-202 trial (ClinicalTrials.gov identifier NCT03070392), in which 378 patients were randomly assigned 2:1 to receive tebentafusp (n = 252) or investigator’s choice of pembrolizumab, ipilimumab, or dacarbazine (n = 126). Tebentafusp was administered weekly by intravenous (IV) infusion at 20 μg on day 1, 30 μg on day 8, 68 μg on day 15, and every week thereafter until disease progression or unacceptable toxicity. Patients with prior systemic therapy or localized liver-directed therapy were excluded, as were those with clinically significant cardiac disease or symptomatic, untreated brain metastases. Prior resection of oligometastatic disease was permitted.

Median overall survival was 21.7 months (95% confidence interval [CI] = 18.6–28.6 months) in the tebentafusp group vs 16 months (95% CI = 9.7–18.4 months) in the investigator’s choice group (hazard ratio [HR] = 0.51, 95% CI = 0.37–0.71, P < .0001). Median investigator-assessed progression-free survival was 3.3 months (95% CI = 3–5 months) vs 2.9 months (95% CI = 2.8–3 months; HR = 0.73, 95% CI = 0.58–0.94, P = .0139).

How It Is Used

The recommended dose of tebentafusp is 20 μg on day 1, 30 μg on day 8, 68 µg on day 15, and 68 µg once weekly thereafter via IV infusion, with treatment continued until disease progression or unacceptable toxicity. No dose reductions are recommended. Product labeling provides instructions on dosage modification for cytokine-release syndrome, skin reactions, elevated liver enzymes, and grade 3 or 4 reactions.

Safety Profile

In the IMCgp100-202 trial, the most common adverse events of any grade (≥ 30%) in the tebentafusp group were cytokine-release syndrome (89%), rash (83%), pyrexia (76%), pruritus (69%), fatigue (64%), nausea (49%), chills (48%), abdominal pain (45%), edema (45%), hypotension (39%), dry skin (31%), headache (31%), and vomiting (30%). The most common grade 3 or 4 adverse events included rash (18%) and fatigue (6%).

Laboratory abnormalities of any grade 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 most common grade 3 or 4 laboratory abnormalities were decreased lymphocyte count (56%), increased lipase (15%), and increased aspartate aminotransferase (13%).

Serious adverse events occurred in 28% of patients, most commonly cytokine-release syndrome (10%), rash (4.5%), pyrexia (2.4%), and hypotension (2%). Adverse events led to treatment discontinuation in 3.3% (anaphylactic reaction, brain edema, cytokine-release syndrome, fatigue, hepatotoxicity, hypotension, and nausea). One patient experienced a fatal adverse event (pulmonary embolism).

Tebentafusp has a boxed warning for cytokine-release syndrome. It has warnings/precautions for skin reactions, elevated liver enzymes, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving tebentafusp. 

REFERENCE

1. Kimmtrak (tebentafusp-tebn) injection, for intravenous use, prescribing information, Immunocore Limited, January 2020. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761228s000lbl.pdf. Accessed February 1, 2022.