The following is a summary of “Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma,” published in the January 2023 issue of Oncology by Chesney, et al.
In phase Ib research, the combination of talimogene laherparepvec (T-VEC) and pembrolizumab showed a promising complete response rate (CRR) in patients with advanced melanoma with an acceptable safety profile. For a study, researchers sought to compare T-VEC with pembrolizumab (T-VEC-pembrolizumab) to placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma. It was a phase III, randomized, double-blind, multicenter, worldwide investigation.
Antiprogrammed cell death protein-1-naive patients with stage IIIB-IVM1c unresectable melanoma were randomly randomized to receive either T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was given at a dosage of ≤4×106 plaque-forming units (PFU), followed by ≤ 4 × 108 PFU three weeks later. After that, T-VEC was given once every two weeks until dose five and once every three weeks after that. Every three weeks, 200 mg of pembrolizumab was delivered intravenously. Progression-free survival (PFS) measured by a blinded independent central review using modified RECIST 1.1 and overall survival (OS) were the two major end objectives. The objective response rate per mRECIST, CRR, and safety were considered secondary end goals. They presented the preliminary analysis for PFS, the second preplanned interim analysis for OS, and the comprehensive analysis.
In all, 692 patients were assigned at random (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). When compared to placebo-pembrolizumab, T-VEC-pembrolizumab did not substantially enhance PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P =.13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P =.74). The T-VEC-pembrolizumab (CRR 17.9%) and placebo-pembrolizumab (CRR 11.6%) groups had objective response rates of 48.6% and 41.3%, respectively, while the respective durable response rates were 42.2% and 34.1%. About 20.7% of patients in the T-VEC-pembrolizumab arm and 19.5% of patients in the placebo-pembrolizumab arm experienced grade ≥3 treatment-related side events.
Comparing T-VEC-pembrolizumab to placebo-pembrolizumab did not substantially enhance PFS or OS. The T-VEC and pembrolizumab combination’s safety outcomes were similar to the safety profiles of each drug used separately.
Reference: ascopubs.org/doi/full/10.1200/JCO.22.00343
