Results of a randomized phase IIb trial of nelipepimut-S + trastuzumab vs trastuzumab to prevent recurrences in high-risk HER2 low-expressing breast cancer patients.

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Clinical cancer research : an official journal of the American Association for Cancer Research


PURPOSE: Preclinical data provide evidence for synergism between HER2-targeted peptide vaccines and trastuzumab. The efficacy of this combination was evaluated in HER2 low-expressing breast cancer patients in the adjuvant setting.

EXPERIMENTAL DESIGN: A phase IIb, multicenter, randomized, single-blinded, controlled trial enrolled disease-free patients after standard therapy completion (NCT01570036). Eligible patients were HLA-A2, A3, A24, and/or A26+, and had HER2 immunohistochemistry 1+/2+, FISH nonamplified breast cancer, that was node positive and/or hormone receptor negative (triple negative breast cancer [TNBC]). Patients received trastuzumab for one year and were randomized to placebo (granulocyte-macrophage colony-stimulating factor [GM-CSF], control) or nelipepimut-S (NPS) with GM-CSF. Primary outcome was 24-month disease-free survival (DFS). Secondary outcomes were 36-month DFS, safety, and immunologic response.

RESULTS: Overall, 275 patients were randomized; 136 received NPS with GM-CSF and 139 received placebo with GM-CSF. There were no clinicopathologic differences between groups. Concurrent trastuzumab and NPS with GM-CSF was safe with no additional overall or cardiac toxicity compared to control. At median follow up of 25.7 (interquartile range, IQR: 18.4-32.7) months, estimated DFS did not significantly differ between NPS and control (HR 0.62, 95% CI: 0.31-1.25, p=0.18). In a planned exploratory analysis of TNBC patients, DFS was improved for NPS vs control (HR 0.26, 95% CI: 0.08-0.81, p=0.01).

CONCLUSION: The combination of NPS with trastuzumab is safe. In HER2 low-expressing breast cancer, no significant difference in DFS was seen in the intention-to-treat analysis; however, significant clinical benefit was seen in TNBC patients. These findings warrant further investigation in a phase III randomized trial.

Clinical Institute


Clinical Institute

Women & Children