Tebentafusp Increases Overall Survival in Metastatic Uveal Melanoma

The study shows the therapy can have a clinically meaningful effect on outcomes, even for patients who have no radiographically significant decrease in tumor size.

In a phase 3 trial, tebentafusp treatment increased overall survival length for patients with metastatic uveal melanoma, according to a publication in the New England Journal of Medicine.

The characteristics that distinguish uveal melanoma, the most common intraocular cancer in adult patients, from cutaneous melanoma may contribute to its lack of response to systemic therapy. The objective of the study (ClinicalTrials.gov number: NCT03070392) was to determine long-term survival benefit of tebentafusp monotherapy.

The researchers included adult patients with confirmed metastatic uveal melanoma who were HLA-A*02:01–positive. The patients had not received systemic or liver-direct therapy.

Patients randomly, intravenously received tebentafusp (n=252) or investigator’s choice of pembrolizumab (n=103), ipilimumab (n=16), or dacarbazine (n=7).

In a phase 2 trial, rash was linked with survival. The researchers therefore compared overall survival of tebentafusp group patients with rash that occurred within 1 week with participants in the control group.

By the first interim analysis, 150 patients (87 tebentafusp group individuals, 63 control individuals) in the intention-to-treat population had died. The 1-year estimate of overall survival was 73% for patients who received tebentafusp and 59% for individuals in the control group. Estimated mean duration of overall survival was 21.7 months for patients who received tebentafusp and 16 months for control group individuals. Hazard ratio for death was 0.51 (P <.001).

Estimated progression-free survival was significantly higher for patients who received tebentafusp treatment compared with those in the control group (at 6 months: 31% vs 19%, HR 0.73 P =.01). Nine percent of patients who received tebentafusp treatment had an objective response (median duration 9.9 months), compared with 5% of the control group individuals (median duration 9.7 months). The tebentafusp treatment group were more likely to have disease control (46%) compared with the control group (27%).

Among patients in whom disease progressed, median duration of overall survival was higher in the tebentafusp group (15.3 months) compared with the control group (6.5 months) (HR for death 0.43).

Rash (83%), pyrexia (76%), pruritus (69%), chills (47%), hypotension (38%), and erythema (23%) were the most common treatment-related adverse events. More tebenetafusp patients (109 patients, or 44%) than control individuals (19 patients, 17%) experienced grade 3 or 4 adverse events. There were no treatment-related deaths, the researchers reported.

Treatment-related adverse events tended to occur (in 57% of patients) in the first 4 weeks of treatment, during dose escalation of tebentafusp, with events decreasing after 3 weeks of treatment. Two percent of patients discontinued trial treatment due to treatment-related adverse events. 

Eighty-nine percent of patients undergoing tebentafusp group experienced cytokine release syndrome. One percent of patients experienced grade 3 or higher cytokine release syndrome.

Rash in the first week of treatment was not an independent predictor of overall survival. 

Disclosure: This research was supported by Immunocore. Please see the original reference for a full list of disclosures.


Nathan P, Hassel JC, Rutkowski P, et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2021;385:1196-206. doi:10.1056/NEJMoa2103485