Talimogene laherparepvec-ipilimumab combo useful in treatment of advanced melanoma
The combination of talimogene laherparepvec plus ipilimumab demonstrates greater antitumour activity in patients with advanced, unresectable melanoma compared with ipilimumab alone, without having additional safety concerns, according to the results on an open-label phase II study.
A total of 198 patients with stages IIIB to IV disease were randomized to receive talimogene laherparepvec plus ipilimumab (n=98) or ipilimumab alone (n=100). Treatment with talimogene laherparepvec was initiated at week 1 (first dose, ≤4 mL × 106 plaque-forming units/mL; after 3 weeks, ≤4 mL × 108 plaque-forming units/mL every 2 weeks). On the other hand, ipilimumab (3 mg/kg every 3 weeks; up to four doses) was started at week 1 in the monotherapy arm and week 6 in the combination arm.
Over a median of 68 weeks of follow-up, the primary endpoint of objective response rate, evaluated by investigators per immune-related response criteria, was 39 percent in the combination arm vs 18 percent in the monotherapy arm (odds ratio, 2.9; 95 percent CI, 1.5 to 5.5; p=0.002).
Responses were observed beyond injected lesions. In particular, visceral lesion reductions were seen in 52 percent of patients in the combination arm vs 23 percent in the monotherapy arm.
Commonly reported adverse events (AEs) included fatigue (combination, 59 percent; monotherapy, 42 percent), chills (combination, 53 percent; monotherapy, 3 percent) and diarrhoea (combination, 42 percent; monotherapy, 35 percent). Grade ≥3 AEs occurred in 45 percent of patients treated with the talimogene laherparepvec-ipilimumab combination and in 35 percent of those who received ipilimumab alone. Fatal AEs occurred in three patients in the combination arm, although none were treatment related.
The present data suggest that the combination of talimogene laherparepvec and a checkpoint inhibitor may have significant clinical utility in treatment of advanced melanoma, researchers said.