Molecular Profile Detail

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Profile Name ERBB2 L869R
Gene Variant Detail

ERBB2 L869R (gain of function)

Relevant Treatment Approaches HER inhibitor (Pan) HER2 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 L869R Advanced Solid Tumor sensitive HER inhibitor (Pan) Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, Vizimpro (dacomitinib) inhibited survival of transformed cells expressing ERBB2 (HER2) L869R in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L869R were resistant to Tagrisso (osimertinib) in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor resistant HER2 Inhibitor Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L869R were resistant to Imbruvica (ibrutinib) in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor resistant HER2 Inhibitor Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L869R were resistant to Tykerb (lapatinib) in culture (PMID: 31588020). 31588020
ERBB2 L869R colorectal adenocarcinoma predicted - resistant HER2 Inhibitor Lapatinib + Trastuzumab Case Reports/Case Series Actionable In a clinical case study, a colorectal carcinoma patient who initially achieved stable disease following treatment with Tykerb (lapatinib) and Herceptin (trastuzumab) developed secondary resistance, presenting with a brain metastasis, and ERBB2 (HER2) L869R was identified in the brain lesion (PMID: 29941010). 29941010
ERBB2 L869R breast cancer sensitive HER2 Inhibitor Neratinib Case Reports/Case Series Actionable In a Phase II trial, Nerlynx (neratinib) treatment resulted in a clinical benefit rate of 31% (5/16) in metastatic breast cancer patients harboring ERBB2 (HER2) mutations, with 1 patient harboring ERBB2 (HER2) L869R achievd stable disease for 24 weeks or more (PMID: 28679771; NCT01670877). 28679771
ERBB2 L869R breast cancer sensitive HER2 Inhibitor Neratinib Preclinical - Cell culture Actionable In a preclinical study, Nerlynx (neratinib) inhibited ERBB2 (HER2) phosphorylation and growth of transformed breast epithelial cells expressing ERBB2 (HER2) L869R in culture (PMID: 28274957). 28274957
ERBB2 L869R Advanced Solid Tumor sensitive HER inhibitor (Pan) Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited survival of transformed cells expressing ERBB2 (HER2) L869R in culture (PMID: 31588020). 31588020
ERBB2 L869R lung adenocarcinoma predicted - resistant HER2 Inhibitor Lapatinib Case Reports/Case Series Actionable In a clinical case study, ERBB2 (HER2) L869R was identified in the lymph node metastasis from a lung adenocarcinoma patient that progressed on Tykerb (lapatinib) therapy (PMID: 27900369). 27900369
ERBB2 L869R Her2-receptor negative breast cancer predicted - sensitive HER2 Inhibitor Neratinib Case Reports/Case Series Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in partial response with a progression-free survival of 3.6 months in a patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) L869R (PMID: 29420467; NCT01953926). 29420467
ERBB2 L869R Advanced Solid Tumor sensitive HER2 Inhibitor TH-4000 Preclinical - Cell culture Actionable In a preclinical study, Tarloxotinib (TH-4000) inhibited survival of transformed cells expressing ERBB2 (HER2) L869R in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor sensitive Nazartinib Preclinical - Cell culture Actionable In a preclinical study, Nazartinib (EGF816) inhibited survival of transformed cells expressing ERBB2 (HER2) L869R in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor sensitive HER2 Inhibitor Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, Pyrotinib inhibited survival of transformed cells expressing ERBB2 (HER2) L869R in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor resistant HER2 Inhibitor Sapitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L869R were resistant to Sapitinib (AZD8931) in culture (PMID: 31588020). 31588020
ERBB2 L869R Advanced Solid Tumor sensitive HER inhibitor (Pan) Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited survival of transformed cells expressing ERBB2 (HER2) L755S in culture (PMID: 31588020). 31588020
ERBB2 L869R breast cancer sensitive HER inhibitor (Pan) Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited ERBB2 (HER2) phosphorylation and growth of transformed breast epithelial cells expressing ERBB2 (HER2) L869R in culture (PMID: 28274957). 28274957
ERBB2 L869R breast cancer resistant HER2 Inhibitor Lapatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed breast cancer cells over expressing ERBB2 (HER2) L869R were resistant to Tykerb (lapatinib) in culture, formed tumors and metastasized readily in xenograft animal models (PMID: 27900369). 27900369
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT02673398 Phase II Neratinib Neratinib in Treating Older Patients With Stage IV HER2-Positive Breast Cancer Active, not recruiting
NCT04172597 Phase II Poziotinib A Study of Poziotinib in Patients With EGFR or HER2 Activating Mutations in Advanced Malignancies Recruiting