Adding talimogene laherparepvec (T-VEC) to pembrolizumab does not improve survival in patients with advanced melanoma, according to results of a phase 3 study published in the Journal of Clinical Oncology.

T-VEC plus pembrolizumab did not improve progression-free survival (PFS) or overall survival (OS), when compared with pembrolizumab alone, in patients with stage IIIB-IVM1c unresectable melanoma.

This phase 3 study ( Identifier: NCT02263508) included 692 patients, all of whom were naïve to anti-PD-1 therapy at baseline. Patients were randomly assigned to T-VEC plus pembrolizumab (n=346) or placebo plus pembrolizumab (n=346). 

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At baseline, the median age in both treatment arms was 64 (overall range, 19-94) years. More than half of patients in each arm were men, more than 90% were White, and more than 75% were enrolled outside the United States. More than 60% of patients were PD-L1-positive, and a similar percentage did not have a BRAF mutation.

The median follow-up for the primary PFS analysis was 25.58 months. Although the median PFS was numerically higher in the T-VEC arm, the between-arm difference was not statistically significant. The median PFS was 14.3 months in the T-VEC arm and 8.5 months in the pembrolizumab-alone arm (hazard ratio [HR], 0.86; 95% CI, 0.71-1.04; P =.13). 

The researchers noted that 3 subgroups of patients had a PFS benefit with T-VEC, including patients enrolled in the United States, patients with baseline lactate dehydrogenase less than or equal to the upper limit of normal, and patients with a baseline sum of the longest diameters of target lesions that was less than or equal to the median. 

On the other hand, none of these subgroups had an OS benefit with T-VEC, and there was no significant difference in OS between the treatment arms in the overall cohort.

The median follow-up for the second interim OS analysis was 31.0 months. The median OS was not reached in the T-VEC arm and was 49.2 months in the pembrolizumab-alone arm (HR, 0.96; 95% CI, 0.76-1.22; P =.74). 

There were no new safety concerns with the addition of T-VEC to pembrolizumab, and the safety profile of the combination was consistent with the safety profiles of each drug, according to the researchers. 

“Although the combination of T-VEC-pembrolizumab did not result in OS benefit compared with placebo-pembrolizumab in the frontline treatment of advanced melanoma, this combination is still under active investigation in patients who are refractory to anti-PD-1 inhibitor therapy for melanoma and other tumor types,” the researchers noted.

Disclosures: This research was supported by Amgen Inc. and Merck Sharp & Dohme LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Chesney JA, Ribas A, Long GV, et al. Randomized, double-blind, placebo-controlled, global phase III trial of talimogene laherparepvec combined with pembrolizumab for advanced melanoma. J Clin Oncol. Published online August 23, 2022. doi:10.1200/JCO.22.00343