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    DRUG:

    Nerlynx (neratinib)

    i
    Other names: HKI-272, PB-272, PB272, PF-0528767, WAY-179272, HKI272, HKI 272, PB 272, PF0528767, PF 0528767, WAY179272, WAY 179272
    Company:
    BIXINK Therapeutics, Boryung Group, Convalife, Er-Kim Pharma, Fosun Pharma, Knight Therap, Pierre Fabre, Puma, Shenzhen Kexing Pharma, Specialised Therap
    Drug class:
    EGFR inhibitor, HER2 inhibitor, HER4 inhibitor
    Related drugs:
    21h
    Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2) (clinicaltrials.gov)
    P2, N=109, Recruiting, Scott R. Plotkin, MD, PhD | Active, not recruiting --> Recruiting
    Enrollment open
    |
    NF2 (Neurofibromin 2)
    |
    Avastin (bevacizumab) • Nerlynx (neratinib) • Alunbrig (brigatinib) • Zynyz (retifanlimab-dlwr)
    16d
    Neratinib + Valproate in Advanced Solid Tumors, w/Expansion Cohort in Ras-Mutated Ca (clinicaltrials.gov)
    P1/2, N=83, Recruiting, Virginia Commonwealth University | Trial completion date: May 2027 --> Jan 2031 | Trial primary completion date: May 2026 --> Dec 2029
    Trial completion date • Trial primary completion date
    |
    GNAQ (G Protein Subunit Alpha Q) • GNA11 (G Protein Subunit Alpha 11)
    |
    RAS mutation
    |
    Nerlynx (neratinib)
    22d
    FGFR2 is a Candidate Immune-Associated Marker of Diabetic Foot Ulcer That Promotes Keratinocyte Function by Activating the PI3K/Akt and MAPK Pathways. (PubMed, Mediators Inflamm)
    FGFR2 is lowly expressed in DFU and can exert a protective effect by activating the PI3K/Akt pathway. It is a candidate diagnostic biomarker and potential therapeutic target for DFU.
    Journal
    |
    FGFR2 (Fibroblast growth factor receptor 2) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha)
    |
    FGFR2 overexpression
    |
    Nerlynx (neratinib) • LY294002 • SB202190
    24d
    Integrative multi-omic analysis identified ERBB2 mutations and senescence-driven immune suppression as dual therapeutic targets in LAR triple-negative breast cancer. (PubMed, Cancer Biol Med)
    The LAR subtype harbors two therapeutic vulnerabilities: ERBB2 mutation-driven kinase activation; and senescence-mediated immune evasion. The LAR-S signature enables precise patient stratification and supports senescence-targeted and immunotherapy combination strategies as promising approaches for this refractory TNBC subtype.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor)
    |
    PIK3CA mutation • HER-2 mutation • PTEN mutation
    |
    Nerlynx (neratinib)
    29d
    Efficacy and Genomic Analysis of HER2-Mutant Metastatic Triple-Negative Breast Cancer Treated with Neratinib Alone or with Trastuzumab in the SUMMIT Basket Trial. (PubMed, Clin Cancer Res)
    N+T in patients with HER2-mutant metastatic TNBC appeared to prolong responses versus neratinib alone, representing a novel approach for biomarker-defined metastatic TNBC patients. Based on these and previously published data, neratinib-based combinations are endorsed by NCCN guidelines for patients with hormone receptor-positive or -negative metastatic breast cancer with activating HER2 mutations.
    Journal • Pan tumor
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    TP53 mutation • KRAS mutation • HR positive • HER-2 mutation
    |
    Herceptin (trastuzumab) • Nerlynx (neratinib)
    1m
    Exploring tyrosine kinase inhibitors for HER2-positive breast cancer: comprehensive review on a complete pharmacology-molecular mechanisms, safety profiles, and insights from preclinical and clinical studies. (PubMed, Clin Transl Oncol)
    They have demonstrated substantial improvements in survival-free and life expectancy of patients, establishing them as a standard treatment modality. The ongoing development of novel tyrosine kinase inhibitors and their strategic integration into personalized treatment regimens will shape the evolving landscape of breast cancer therapy.
    Preclinical • Review • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive
    |
    lapatinib • Nerlynx (neratinib) • Irene (pyrotinib)
    1m
    Integrated Multi-omic Profiling Identifies BRD8/EP400 as a Pivotal Chromatin Module Mediating Anti-HER2 Response in HR+/HER2+ Breast Cancer. (PubMed, Cancer Res)
    BRD8 regulated ER-dependent and independent growth pathways, and depletion of BRD8 abolished neratinib-induced ER activation and restored drug sensitivity in resistant cells. A 3-gene BRD8 signature successfully predicted anti-HER2 therapy response in two human clinical trials. Together, these findings establish BRD8 as both a predictive biomarker for anti-HER2 response and a therapeutic target to overcome resistance in HR+/HER2+ breast cancer.
    Journal
    |
    ER (Estrogen receptor) • EP400 (E1A Binding Protein P400)
    |
    HER-2 positive • HR positive • HR positive + HER-2 positive
    |
    Nerlynx (neratinib)
    2ms
    Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Breast Cancers (clinicaltrials.gov)
    P2, N=30, Recruiting, Ruth O'Regan | Trial completion date: Jan 2026 --> Jul 2027 | Trial primary completion date: Dec 2025 --> Jun 2026
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    HER-2 positive • ER positive • PGR positive
    |
    Herceptin (trastuzumab) • Nerlynx (neratinib) • letrozole • anastrozole
    2ms
    Enhanced Payload Release Enables Disitamab Vedotin to Surpass Trastuzumab Emtansine and Retain Efficacy in Acquired Resistance to Clinical Anti-HER2 Therapies. (PubMed, Pharmaceutics)
    Notably, RC48 retained strong activity in BT474-derived sublines resistant to T-DM1, lapatinib, or neratinib, inducing cell cycle arrest, apoptosis, and caspase activation in all resistant models. Together, these findings identify disitamab vedotin as a potent next-generation HER2-targeting ADC with the unique capacity to overcome acquired resistance to HER2-directed therapies. RC48 represents a promising therapeutic strategy for patients with refractory HER2-positive breast cancer and warrants further clinical investigation.
    Preclinical • Journal
    |
    CCNB1 (Cyclin B1)
    |
    HER-2 positive • HER-2 overexpression • HER-2 positive + HER-2 overexpression
    |
    lapatinib • Nerlynx (neratinib) • Kadcyla (ado-trastuzumab emtansine) • Aidixi (disitamab vedotin)
    3ms
    NCI 10495: Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene (clinicaltrials.gov)
    P1, N=33, Suspended, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027 | Recruiting --> Suspended
    Trial completion date • Trial suspension
    |
    CD4 (CD4 Molecule)
    |
    HER-2 positive • HER-2 overexpression • HER-2 amplification • HER-2 mutation
    |
    Nerlynx (neratinib) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    3ms
    TBCRC 022: HKI-272 for HER2-Positive Breast Cancer and Brain Metastases (clinicaltrials.gov)
    P2, N=140, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed
    Trial completion
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive • HER-2 amplification
    |
    Nerlynx (neratinib) • Kadcyla (ado-trastuzumab emtansine) • capecitabine
    4ms
    NCI-2018-01218: Neratinib and Everolimus, Palbociclib, or Trametinib in Treating Participants With Refractory and Advanced or Metastatic Solid Tumors With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation (clinicaltrials.gov)
    P1, N=93, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2025 --> Oct 2028 | Trial primary completion date: Oct 2025 --> Oct 2028
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
    |
    KRAS mutation • EGFR mutation • HER-2 amplification • EGFR amplification
    |
    Mekinist (trametinib) • Ibrance (palbociclib) • everolimus • Nerlynx (neratinib)