Abstract P4-07-23: Results of a Phase 2 Trial of Combination Immunotherapy with Concurrent Nelipepimut-S + GM-CSF and Trastuzumab in High-risk HER2+ Breast Cancer Patients
Authors: Tiwari Ankur , Clifton Guy , Calfa Carmen , Alatrash Gheath , Holmes Jarrod , Bedrosian Isabelle , Peoples George , Mittendorf Elizabeth A. 
Published: March 2023

Abstract
INTRODUCTION: The HER2-targeted peptide vaccine nelipepimut-S + GM-CSF (NeuVax) has been shown to be safe, immunogenic, and potentially synergistic with trastuzumab. Here we present the results of a randomized phase 2 trial assessing the ability of nelipepimut-S/GM-CSF versus GM-CSF alone, added to the standard adjuvant Trastuzumab, to prevent recurrences in high-risk HER2-positive breast cancer patients. METHODS: The study was a multi-center, prospective, randomized, controlled, single-blinded, phase 2 trial. Enrolled patients had high risk HER2+ breast cancer defined by the presence of residual disease post neoadjuvant therapy or by the presence of positive lymph nodes after upfront surgery. Eligible patients had completed an approved trastuzumab-chemotherapy containing regimen and they were receiving adjuvant Trastuzumab monotherapy. Enrollment was limited to patients with HLA-A2, A3, A24, and/or A26 alleles. Patients received intradermal injections of nelipepimut-S + GM-CSF or placebo + GM-CSF every three weeks for six total vaccinations with concurrent, standard monotherapy with iv trastuzumab. After completion of the primary vaccine series, booster inoculations were administered every six months for four doses. The primary outcome measure was invasive disease-free survival (iDFS) at 36 months. Secondary outcome measures were distant recurrence-free survival (DRFS), toxicity assessment, and evaluation of immune response. RESULTS: 100 patients were enrolled and randomized 1:1 to nelipepimut-S/GM-CSF or GM-CSF alone. There were no significant clinicopathologic differences between the groups. There was no difference in related local (p=0.49) or systemic toxicities (p=0.41). Kaplan-Meier estimates of iDFS at 36 months were 79% in the nelipepimut-S arm and 92% in the placebo arm (log rank, p=0.11). DRFS at 36 months was estimated to be 90% in the nelipepimut-S arm and 95% in the placebo arm (log rank, p=0.40). Delayed type hypersensitivity (DTH) response to nelipepimut-S was measured and considered positive if there was more than 5 mm induration after 48 hours. DTH response converted from negative to positive in 11% of patients in the vaccine group versus 5% of patients in the placebo group (p=0.36). In both groups, iDFS at 36 months was 100% for those with a positive DTH response post-inoculation and 88% for those with a negative DTH response post-inoculation (log rank, p=0.29). CONCLUSION: Combination immunotherapy with concurrent nelipepimut-S + GM-CSF and trastuzumab is safe, however there was no difference in iDFS or DRFS among high-risk HER2+ breast cancer patients who received nelipepimut-S + GM-CSF compared to GM-CSF alone. We observed a trend towards improved iDFS in patients with a positive DTH response to nelipepimut-S, though it was not statistically significant.
Citation Format: Ankur Tiwari, Guy Clifton, Carmen Calfa, Gheath Alatrash, Jarrod Holmes, Isabelle Bedrosian, George Peoples, Elizabeth A. Mittendorf. Results of a Phase 2 Trial of Combination Immunotherapy with Concurrent Nelipepimut-S + GM-CSF and Trastuzumab in High-risk HER2+ Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-23.