Nelipepimut-S

NeuVax, E75, nelipepimut-S, HER2/neu 369–377 (sequence KIFGSLAFL)

Oncology & imaging

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Nelipepimut-S is an investigational cancer vaccine given only inside clinical trials under oncology supervision. It is not available or used outside trials, and nothing here describes self-preparation.

Summary

Class: Synthetic nine-amino-acid HLA-A2/A3-restricted class I peptide from the extracellular domain of HER2 (ERBB2), given with recombinant GM-CSF (sargramostim) as the adjuvant
Mechanism: Expands HER2-specific CD8+ T cells so they can recognise and kill residual HER2-expressing breast-cancer cells after surgery and chemotherapy
Routes studied: Intradermal injection, peptide mixed with GM-CSF, monthly for six primary doses then booster injections
Half-life: Not a meaningful figure; the peptide is cleared rapidly and the GM-CSF depot and T-cell response are what matter
Storage: Trial pharmacy product; peptide and GM-CSF reconstituted and mixed immediately before each injection
Regulatory status: Not approved anywhere. Development for the lead indication halted in 2016. See region table

Doses are as reported in studies or by the community — never recommendations.

1What it is

Nelipepimut-S is a single nine-amino-acid fragment of HER2, the growth-factor receptor that is amplified in roughly 15–20% of breast cancers and targeted by trastuzumab. The peptide, known in the older literature as E75, binds HLA-A2 and HLA-A3 — together covering a majority of patients of European ancestry — and was developed as a post-surgical "clean-up" vaccine for women at high risk of recurrence whose tumours expressed HER2 at any level, including the low-expressing tumours that do not qualify for trastuzumab.

It became the most advanced single-peptide cancer vaccine ever tested in breast cancer, and its phase 3 failure is a central data point in the field.

2How it's thought to work

GM-CSF injected with the peptide recruits and matures dendritic cells at the intradermal injection site.

Those cells present the HER2 peptide, expanding circulating HER2-specific CD8+ cytotoxic T cells.

Those T cells are expected to find and kill micrometastatic HER2-expressing tumour cells, which are too few to detect but are the source of later recurrence.

The approach requires both the right HLA type and continued HER2 expression on the residual cells; trial experience suggests the induced response wanes within months without boosters, which is why the booster schedule was added.

A nine-amino-acid HER2 fragment with GM-CSF, intended to prevent recurrence after breast cancer treatment. The main phase III was stopped for futility.Schematic — not to scale

3What the research shows

Graded A (negative)

Node-positive, HER2-low breast cancer, adjuvant setting

The PRESENT trial (NCT01479244) randomised women with node-positive, HER2 1+/2+ (immunohistochemistry), HLA-A2/A3-positive breast cancer to nelipepimut-S plus GM-CSF or GM-CSF alone after standard therapy. An independent data monitoring committee recommended stopping the trial for futility in mid-2016, and the sponsor discontinued the programme in that indication. This is the pivotal result and the honest summary of the compound: a properly powered randomised phase 3 found no disease-free survival benefit.

Earlier phase 1/2 experience

Pooled single-arm and small randomised phase 1/2 studies in node-positive and high-risk node-negative patients reported a lower recurrence rate in vaccinated than in unvaccinated observation patients at five years (roughly 5–10% vs 15–20% in various analyses), with reliable induction of HER2-specific T cells (Mittendorf 2014, Ann Oncol; Peoples 2005/2008 series). These were not randomised against a matched control with the same follow-up discipline, and the phase 3 did not reproduce them — a textbook case of a promising phase 2 signal that did not survive randomisation. [1][4]

Graded A/B (negative overall, subgroup signal)

Combination with trastuzumab

A randomised phase 2b trial added nelipepimut-S plus GM-CSF or GM-CSF alone to trastuzumab in HER2-low, high-risk patients. There was no significant disease-free survival benefit in the overall population; an unplanned subgroup analysis in triple-negative breast cancer suggested fewer recurrences (Clifton 2020, Clin Cancer Res). Hypothesis-generating only, and never confirmed in a dedicated trial. [3]

Ductal carcinoma in situ and other settings

Small neoadjuvant and DCIS studies reported immune responses and some pathological changes. Numbers are too small for efficacy conclusions.

4Reported side effects and interactions

Literature-reported

the dominant adverse events were local — injection-site erythema, induration, pruritus and sometimes blistering, driven largely by the GM-CSF. Flu-like symptoms, fatigue, bone pain and low-grade fever. Grade 3+ events were uncommon. No cardiotoxicity signal, which was a specific concern given the HER2 target and trastuzumab's cardiac profile; left ventricular function was monitored and did not deteriorate attributably in the reported series.

Community-reported

Community use: essentially none documented.

Theoretical. autoimmunity against normal HER2-expressing tissue (heart, gut epithelium) was the principal worry and did not materialise in trials at the doses used.

Interactions. trastuzumab (studied together); corticosteroids and immunosuppressants would be expected to blunt the response; concurrent cytotoxic chemotherapy was generally avoided during the primary vaccination series.

Markers researchers commonly monitor

From the trial protocols:

Marker	Why it's watched
HLA-A2/A3 genotype and tumour HER2 immunohistochemistry	eligibility gates; the mechanism fails without both.
HER2-specific CD8+ T-cell frequency (ELISpot, dextramer)	the immunological readout; it rose reliably and still did not translate into benefit, which is the main lesson of this programme.
Delayed-type hypersensitivity reaction size at the injection site	used as a cheap in-vivo marker of response.
Disease-free and overall survival, with imaging per protocol	the only clinically meaningful endpoints.
Left ventricular ejection fraction (echocardiogram)	monitored because of the HER2 target and concurrent trastuzumab, not because a signal was found.
CBC and CMP	routine oncology safety monitoring.

Free for everyone. Safety information is never behind a paywall.

5Formulation and administration context

Supplied to trial sites as peptide, and drawn up with reconstituted GM-CSF immediately before each injection and given intradermally, typically split between two sites, by trained staff. HLA-A2/A3 typing and HER2 immunohistochemistry were eligibility requirements. Local reactions were deliberately expected — a visible wheal was taken as a sign of adjuvant activity. There is no self-prepared, compounded or outpatient version of this product and no dose calculation appropriate to publish.

6Commonly studied alongside

Trastuzumab; GM-CSF (sargramostim) as adjuvant; GP2 and AE37 (two other HER2-derived peptide vaccines from the same research lineage, both negative on their primary endpoints in randomised phase 2). Conceptually related: gp100 peptide vaccine (profile 231), IMA901 and multi-peptide tumour vaccines (profile 236).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; investigational. Phase 3 halted for futility 2016; no active registration path in the original indication †
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered with SAHPRA
Sport	Not listed by WADA; no performance application

8Open questions

Why did a consistent, measurable T-cell response produce no clinical benefit? Immunosuppressive tumour microenvironment, antigen loss, and short-lived effector T cells are all proposed.
Is the triple-negative subgroup signal from the trastuzumab combination real? Untested in a dedicated randomised trial.
Do single class I peptides have any future in adjuvant oncology, or is multi-epitope or neoantigen vaccination the only viable direction?

9References

1Mittendorf EA et al. (2014). Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. Annals of Oncology. PubMed · DOI
2Mittendorf EA et al. (2019). Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide GP2 vaccine — comparative context. Annals of Oncology. PubMed
3Clifton GT et al. (2020). Results of a randomized phase IIb trial of nelipepimut-S + trastuzumab versus trastuzumab to prevent recurrences in patients with high-risk HER2 low-expressing breast cancer. Clinical Cancer Research. PubMed · DOI
4Peoples GE et al. (2008). Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients. Journal of Clinical Oncology. PubMed
5Galena Biopharma (2016). Discontinuation of the PRESENT phase 3 trial following independent data monitoring committee futility analysis — sponsor announcement. PubMed
6ClinicalTrials.gov. NCT01479244 — PRESENT: Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

31 Oct 2026Profile published — awaiting medical review

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