Talimogene laherparepvec (T-VEC) in combination (combo) with ipilimumab (ipi) versus ipi alone for advanced melanoma: 3-year landmark analysis of a randomized, open-label, phase II trial

Abstract

This is the 1st and only randomized trial testing the addition of an oncolytic virus to an immune checkpoint inhibitor in advanced MEL. The study met its primary endpoint: the combo of T‐VEC plus ipi resulted in a significantly higher objective response rate (ORR) vs. ipi alone (39% vs. 18%; OR, 2.9; 95% Cl, 1.5‐5.5; p = 0.002) (Chesney et al. J Clin Oncol. 2017). Here, we present 3‐yr analysis. Pts with unresectable, stages IIIB to IV MEL were randomized 1:1 to combo or ipi alone. T‐VEC was injected intratumorally on d 1 of wk 1 at 106 plaque‐forming units (PFU)/mL followed by subsequent doses at 108 PFU/mL on d 1 of wk 4, and every 2 wks thereafter. IV ipi (3 mg/kg) was given every 3 wks starting on d 1 of wk 6 for up to 4 doses. Response was assessed by investigators per irRC until PD. The primary endpoint was ORR; key secondary endpoints were PFS, OS, and safety. This analysis occurred 36 months (mos) after the last pt was randomized. 198 pts were randomized (98 combo; 100 ipi). As of 25 Feb 2019, the median follow‐up was 40.0 mos in combo arm and 34.3 mos in the ipi arm. ORR was 36.7% with combo and 16.0% with ipi (OR, 3.0; 95% CI, 1.6 to 6.0; p = 0.002). Median PFS was 13.5 mos with combo and 4.5 mos with ipi (HR, 0.78; 95% Cl, 0.55‐1.11; p = 0.159). Median OS was not reached in either arm (HR, 0.85; 95% CI, 0.55‐1.32; p = 0.480). 45 pts (45.9%) in combo arm and 64 (64%) in ipi arm received subsequent anticancer therapy, with median time from randomization to the 1st subsequent therapy being 27.7 mos and 8.3 mos, respectively. No new safety signals were detected. At 3‐yr follow‐up, T‐VEC plus ipi combo continued to provide durable and statistically superior ORR vs. ipi alone. PFS was numerically longer with the combo than ipi. Survival is likely confounded by subsequent therapies.