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Patients with previously untreated metastatic uveal melanoma who also harbored HLA-A*02:01 and were treated with tebentafusp experienced a longer overall survival compared with the control group of a phase 3 clinical trial.
Longer overall survival (OS) was found with the use of tebentafusp (IMCgp100) compared with the control treatment for patients with previously untreated metastatic uveal melanoma who also harbored HLA-A*02:01, according to results from a phase 3 trial (NCT03070392) published in the New England Journal of Medicine.
The 1-year OS rate was 73% in the tebentafusp arm compared with 59% in the control group (HR, 0.51; 95% CI, 0.37-0.71; P <.001). Moreover, the 6-month progression-free survival (PFS) rate in the tebentafusp group was 31% compared with 19% in the control group (HR, 0.73; 95% CI, 0.58-0.94; P =.01).
A total of 378 patients were enrolled on the trial and were randomized 2:1 to either the tebentafusp group (n = 252) or the control group (n = 126). In order to be eligible for tebentafusp, patients needed to have previously untreated patients with HLA-A*02:01–positive metastatic uveal melanoma. Of the patients included in the study, 36% had a lactate dehydrogenase level above the upper limit of the normal range, and 5% had extrahepatic disease only. The median time from diagnosis was 2.8 years. At the first interim analysis, the median duration of follow-up was 14.1 months.
Tebentafusp was administered intravenously at 20 μg on day 1, 30 μg on day 8, and 68 μg for every week thereafter. Additionally, 2 mg/kg of intravenous pembrolizumab (Keytruda) per body weight was given up to a dose of 200 mg or a fixed dose of 200 mg on day 1 of each 21-day cycle. Moreover, ipilimumab was given at a dose of 3 mg/kg on day 1 of each 21-day cycle up to 4 doses, and dacarbazine was given at a dose of 1000 mg per square meter of body surface area on day 1 of every 21-day cycle.
The study’s primary end point was OS.
At the data cutoff during the interim analysis, 150 patients had died, including 87 in the tebentafusp group, and 63 in the control group. The estimated median duration of OS was 21.7 months (95% CI, 18.6-28.6) in the tebentafusp group and 16.0 months (95% CI, 9.7-18.4) in the control group (HR, 0.51; 95% CI, 0.37-0.71; P <.001).
Additional findings from the study indicated that patients in the tebentafusp group experienced an objective response rate of 9% (95% CI, 6%-13%) and 5% (95% CI, 2%-10%) in the control group. Moreover, the median duration of response was 9.9 months in the tebentafusp group and 9.7 months in the control group. The disease control in the tebentafusp group was 46% (95% CI, 39%-52%) and 27% (95% CI, 20%-36%) in the control group.
In terms of those who achieved disease progression as a best response before day 100, treatment with tebentafusp was associated with an estimated median duration of OS of 15.3 months (95% CI, 12.0–not reached) compared with 6.5 months (95% CI, 4.9-13.4) in the control group (HR, 0.43; 95% CI, 0.27-0.68).
More patients in the tebentafusp group experienced tumor regression that did not meet RECIST criteria for partial response in comparison to the control group. For both groups, tumor regression was associated with longer OS.
In terms of safety, grade 3/4 treatment-related adverse effects (TRAEs) were reported in 44% (n = 109) of patients in the tebentafusp group and 17% (n = 19) in the control group. There were no treatment-related deaths reported for either group.
Among those treated with tebentafusp, 57% of TRAEs occurred during the first 4 weeks of treatment during intrapatient dose escalation. After 3 weeks of treatment, the majority of patients transitioned to receive tebentafusp on an outpatient basis with no unacceptable toxic effects.
Cytokine release syndrome (CRS) occurred in 89% of patients in the tebentafusp group; comparatively, 1% of those in the control arm experienced grade 3 CRS. A total of 149 patients developed a rash within 1 week of treatment with tebentafusp.
Patients had an anti-tebentafusp antibody frequency of 29% (n = 63) and 6% (n = 13) experienced a decrease in tebentafusp serum concentration. The anti-tebentafusp antibodies had no effect on OS and was not associated with an increased risk in hypersensitivity reactions.
Nathan P, Hassel JC, Rutkowski P, et al; IMCgp100-202 Investigators. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2021;385(13):1196-1206. doi:10.1056/NEJMoa2103485