Efficacy and Safety Analysis of Nelipepimut-S Vaccine to Prevent Breast Cancer Recurrence: A Randomized, Multicenter, Phase III Clinical Trial.

Purpose: In phase I/II studies, nelipepimutS (NPS) plus GMCSF vaccine was well tolerated and effectively raised HER2specific immunity in patients with breast cancer. Results from a prespecified interim analysis of a phase III trial assessing NPS + GMCSF are reported. Patients and Methods: This multicenter, randomized, doubleblind phase III study enrolled females >= 18 years with T1T3, HER2 lowexpressing (IHC 1+/2+), node-positive breast cancer in the adjuvant setting. Patients received 1,000 mg NPS + 250 mg GMCSF or placebo + GMCSF monthly for 6 months, then every 6 months through 36 months. The primary objective was diseasefree survival (DFS). Protocolspecified imaging occurred annually. New abnormalities were categorized as recurrence events; biopsy confirmation was not mandated. The interim analysis was conducted as specified in the protocol after 73 DFS events. Results: A total of 758 patients (mean age 51.8 years) were randomized. Adverse events were similar between groups; most common were injectionassociated: erythema (84.3%), induration (55.8%), and pruritus (54.9%). There was no significant betweenarms difference in DFS events at interim analysis at median followup (16.8 months). In the NPS arm, imaging detected 54.1% of recurrence events in asymptomatic patients versus 29.2% in the placebo arm (P = 0.069). Conclusions: NPS was well tolerated. There was no significant difference in DFS events between NPS and placebo. Use of mandated annual scans and imagedetected recurrence events hastened the interim analysis contributing to early trial termination.