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

Abstract Purpose: In phase I/II studies, nelipepimut-S (NP-S) plus GM-CSF vaccine was well tolerated and effectively raised HER2-specific immunity in patients with breast cancer. Results from a prespecified interim analysis of a phase III trial assessing NP-S + GM-CSF are reported. Patients and Methods: This multicenter, randomized, double-blind phase III study enrolled females ≥18 years with T1–T3, HER2 low–expressing (IHC 1+/2+), node-positive breast cancer in the adjuvant setting. Patients received 1,000 μg NP-S + 250 μg GM-CSF or placebo + GM-CSF monthly for 6 months, then every 6 months through 36 months. The primary objective was disease-free survival (DFS). Protocol-specified 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 injection-associated: erythema (84.3%), induration (55.8%), and pruritus (54.9%). There was no significant between-arms difference in DFS events at interim analysis at median follow-up (16.8 months). In the NP-S arm, imaging detected 54.1% of recurrence events in asymptomatic patients versus 29.2% in the placebo arm (P = 0.069). Conclusions: NP-S was well tolerated. There was no significant difference in DFS events between NP-S and placebo. Use of mandated annual scans and image-detected recurrence events hastened the interim analysis contributing to early trial termination.