NeuVax (nelipepimut-S)

P2, N=43, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Mar 2024 --> May 2023

Research was carried out on the following databases: PubMed, EMBASE, ClinicalTrial.gov, Medline, and Web of Science for the terms "radiotherapy", "radiation therapy", "radiosurgery", "local ablative therapy", and "stereotactic", combined with "trastuzumab", "pertuzumab", "trastuzumab emtansine", "TDM-1", "T-Dxd", "trastuzumab deruxtecan", "tucatinib", "lapatinib", "immune checkpoint inhibitors", "atezolizumab", "pembrolizumab", "nivolumab", "E75 vaccine", "interferon", "anti-IL-2", "anti-IL 12", and "ADC". HER2-targeting monoclonal antibodies and checkpoint inhibitors can be combined with radiation, apparently with no excess toxicities. Caution is required when associating radiation with TKI and antibody drugs, considering the limited evidence.

P2, N=43, Active, not recruiting, National Cancer Institute (NCI) | N=13 --> 43

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.

P2, N=100, Completed, Cancer Insight, LLC | Active, not recruiting --> Completed

The E75 vaccine was effective and safe in patients with breast cancer. The GP2 vaccine could elicit a strong immune response, but more trials are needed to confirm its clinical efficacy.

Although, commonly used treatments like trastuzumab/pertuzumab for human epidermal growth factor receptor 2 (Her2) positive and hormone therapy for estrogen receptor (ER) positive and/or progesterone receptor (PR) positive BC are specific but triple negative breast cancer (TNBC) cases remain a great challenge for treatment measures. Immune checkpoint inhibitors (anti-PD-1/ anti-CTLA-4) and anti-cancer vaccines (NeuVax, Muc-1, AVX901, INO-1400 and CEA), either alone or in combination with other therapies have created new paradigm in therapeutic world. In this review, we highlighted the current immunotherapeutic aspects and their ongoing trials towards the better treatment regimen for BC.

P2, N=100, Active, not recruiting, Cancer Insight, LLC | Trial completion date: Mar 2021 --> Dec 2021 | Trial primary completion date: Mar 2021 --> Dec 2021

NPS vaccination with trastuzumab was associated with improved 36-month DFS among patients with TNBC. The observed benefit to this high-risk subgroup warrants confirmation in a phase III trial.

The current leading peptide vaccine for human application is a HER2-based vaccine known as Nelipepimut-S, which has demonstrated immune activity and promising clinical activity in some settings. This review covers the development of this newer peptide vaccine for both HER2 amplified and non-amplified breast cancer.

P1, N=100, Completed, COL George Peoples, MD, FACS | Phase classification: P1/2 --> P1

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.

P2, N=100, Active, not recruiting, Cancer Insight, LLC | Trial completion date: Dec 2020 --> Mar 2021 | Trial primary completion date: Dec 2019 --> Mar 2021