Chesney J, et al. - Experts undertook a comparative analysis of the combination of talimogene laherparepvec plus ipilimumab vs ipilimumab alone in patients with advanced melanoma. Findings illustrated a substantially higher objective response rate with talimogene laherparepvec plus ipilimumab when compared to ipilimumab alone. Such a combination displayed greater antitumor activity without additional safety concerns than ipilimumab.

Methods

• The eligible candidates included individuals with unresectable stages IIIB to IV melanoma, with no more than one prior therapy if BRAF wild-type, no more than two prior therapies if BRAF mutant, measurable/injectable disease, and without symptomatic autoimmunity or clinically significant immunosuppression.
• They were randomly allocated 1:1 to receive talimogene laherparepvec plus ipilimumab or ipilimumab alone.
• During this trial, talimogene laherparepvec therapy began in week 1 (first dose, ≤ 4 mL × 106 plaque-forming units/mL; after 3 weeks, ≤ 4 mL × 108 plaque-forming units/mL every 2 weeks).
• Ipilimumab (3 mg/kg every 3 weeks; up to 4 doses) began week 1 in the ipilimumab alone arm and week 6 in the combination arm.
• Analysis of objective response rate by investigators per immune-related response criteria served as the primary end point.

Results

• Experts randomly allocated 198 subjects to talimogene laherparepvec plus ipilimumab (n = 98), or ipilimumab alone (n = 100).
• An objective response was achieved in 38 patients (39%) in the combination arm and 18 patients (18%) in the ipilimumab arm (odds ratio, 2.9; 95% CI, 1.5 to 5.5; P=.002).
• It was determined that responses were not limited to injected lesions.
• Decreases in visceral lesion were revealed in 52% of patients in the combination arm and 23% of patients in the ipilimumab arm.
• Fatigue (combination, 59%; ipilimumab alone, 42%), chills (combination, 53%; ipilimumab alone, 3%), and diarrhea (combination, 42%; ipilimumab alone, 35%) were found to be the frequently occurring adverse events (AEs).
• Data illustrated that the incidence of grade ≥ 3 AEs was 45% and 35%, respectively.
• Fatal AEs were reported among 3 subjects in the combination arm, neither appeared to be treatment related.