Nelipepimut-S

Summary

Nelipepimut-S (NPS, E75) is a 9-amino acid HER2/neu-derived peptide vaccine candidate being investigated for the prevention of breast cancer recurrence in HER2-low to intermediate expressing patients. It is typically administered with GM-CSF as adjuvant. Clinical trials have explored its use in early-stage breast cancer patients following standard-of-care treatment.

Mechanism of Action

Nelipepimut-S (E75) is a HER2/neu-derived peptide (KIFGSLAFL) that stimulates cytotoxic T lymphocyte (CTL) responses. When combined with GM-CSF adjuvant, it activates CD8+ T cells to recognize and destroy HER2-expressing tumor cells via MHC class I presentation, inducing HER2-specific immune surveillance.

Routes of Administration

Goals & Uses

• Prevention of breast cancer recurrenceOncology / Cancer PreventionModerate
• Adjuvant therapy in node-positive breast cancerOncologyLow
• Combination with trastuzumab for HER2-low breast cancerCombination ImmunotherapyModerate
• HER2-specific immune activationImmunotherapyModerate

Contraindications

• HLA-A2 or HLA-A3 negativityGenetic/ImmunologicHigh
• Immunosuppressive therapyPharmacologicalModerate
• Known hypersensitivity to GM-CSF or vaccine componentsAllergicHigh
• Active autoimmune diseaseAutoimmunityHigh

Adverse Effects

• Flu-like symptomsSystemic/ImmunologicalUncommon
• Local Injection Site ReactionsDermatologicalCommon
• FatigueGeneralCommonLow energy or tiredness
• Allergic/hypersensitivity reactionsImmunologicalRare
• LymphadenopathyLymphoreticularUncommon

Drug Interactions

• Chemotherapy agentsModerate
• TrastuzumabLow
• CorticosteroidsModerate

Population Constraints

• Pregnant or breastfeeding womenReproductiveRelative
• Severely immunocompromised patientsImmunologicalRelative
• HER2-overexpressing (3+) breast cancerOncologicRelative
• HLA-A2 or HLA-A3 negative patientsGeneticAbsolute

Regulatory Status

• European UnionInvestigationalNo EMA approval; remains in clinical investigation.
• United StatesInvestigationalReceived FDA Breakthrough Therapy Designation for prevention of recurrence of HER2-low expressing breast cancer in combination with trastuzumab. Not approved. Phase III PRESENT trial did not meet primary endpoint.
• United KingdomInvestigationalNo MHRA approval; investigational only.

Nelipepimut-S received Breakthrough Therapy Designation from the FDA for the prevention of recurrence of HER2-low expressing breast cancer in combination with trastuzumab. It has not yet received full FDA approval. Phase III trial (PRESENT trial) did not meet its primary endpoint.

Evidence & Sources

No sources recorded yet.