Molecular Profile Detail

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Profile Name ERBB2 L755P
Gene Variant Detail

ERBB2 L755P (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 L755P Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L755P were resistant to Tagrisso (osimertinib) in culture (PMID: 31588020). 31588020
ERBB2 L755P Advanced Solid Tumor resistant HER2 Inhibitor Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L755P were resistant to Pyrotinib in culture (PMID: 31588020). 31588020
ERBB2 L755P Advanced Solid Tumor sensitive WZ4002 Preclinical Actionable In a preclinical study, WZ4002 inhibited proliferation of transformed cell lines expressing ERBB2 (HER2) L755P in culture (PMID: 22046346). 22046346
ERBB2 L755P Advanced Solid Tumor resistant Nazartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L755P were resistant to Nazartinib (EGF816) in culture (PMID: 31588020). 31588020
ERBB2 L755P Advanced Solid Tumor resistant HER2 Inhibitor Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L755P were resistant to Imbruvica (ibrutinib) in culture (PMID: 31588020). 31588020
ERBB2 L755P lung non-small cell carcinoma no benefit HER2 Inhibitor Neratinib Case Reports/Case Series Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 14.8 months in a patient with non-small cell lung cancer harboring ERBB2 (HER2) L755P (PMID: 29420467; NCT01953926). 29420467
ERBB2 L755P Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cell lines expressing ERBB2 (HER2) L755P demonstrated resistance when treated with Tykerb (lapatinib) in culture (PMID: 22046346). 22046346
ERBB2 L755P Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L755P were resistant to Tykerb (lapatinib) in culture (PMID: 31588020). 31588020
ERBB2 L755P Advanced Solid Tumor resistant HER2 Inhibitor Neratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L755P were resistant to Nerlynx (neratinib) in culture (PMID: 31588020). 31588020
ERBB2 L755P Advanced Solid Tumor resistant HER inhibitor (Pan) Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L755P were resistant to Gilotrif (afatinib) in culture (PMID: 31588020). 31588020
ERBB2 L755P lung non-small cell carcinoma predicted - sensitive HER2 Inhibitor Pyrotinib Case Reports/Case Series Actionable In a Phase II trial, a patient with non-small cell lung cancer harboring ERBB2 L755P demonstrated a partial response when treated with Pyrotinib (PMID: 30596880; NCT02535507). 30596880
ERBB2 L755P lung non-small cell carcinoma predicted - sensitive HER2 Inhibitor Pyrotinib Case Reports/Case Series Actionable In a Phase II trial, Pyrotinib treatment resulted in an objective response rate of 25% (1/4) in non-small cell lung cancer patients harboring ERBB2 (HER2) L755P who had received prior platinum-based chemotherapy (PMID: 32614698; NCT02834936). 32614698
ERBB2 L755P Advanced Solid Tumor sensitive HER2 Inhibitor Tarloxotinib Preclinical - Cell culture Actionable In a preclinical study, Tarloxotinib (TRLX) inhibited survival of transformed cells expressing ERBB2 (HER2) L755P in culture (PMID: 31588020). 31588020
ERBB2 L755P lung adenocarcinoma no benefit Ado-trastuzumab emtansine Case Reports/Case Series Actionable In a Phase II trial, treatment with Kadcyla (trastuzumab emtansine) resulted in best overall responses of partial response in 44% (8/18) and stable disease in 39% (7/18), and median progression-free survival of 5 months in patients with lung adenocarcinoma harboring ERBB2 (HER2) activating mutations, but a subset of patients specifically harboring ERBB2 L755P (2/2) did not demonstrate a partial response (PMID: 29989854; NCT02675829). 29989854
ERBB2 L755P lung non-small cell carcinoma predicted - sensitive HER inhibitor (Pan) Poziotinib Case Reports/Case Series Actionable In a Phase II trial, Poziotinib (HM781-36B) treatment resulted in stable disease lasted more than 7 months in a patient with non-small cell lung cancer harboring ERBB2 (HER2) L755P (PMID: 31588020; NCT03066206). 31588020
ERBB2 L755P Advanced Solid Tumor sensitive EKI-785 Preclinical Actionable In a preclinical study, EKI-285 (CL-387785) inhibited proliferation of transformed cell lines expressing ERBB2 (HER2) L755P in culture (PMID: 22046346). 22046346
ERBB2 L755P Advanced Solid Tumor resistant HER2 Inhibitor Sapitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L755P were resistant to Sapitinib (AZD8931) in culture (PMID: 31588020). 31588020
ERBB2 L755P Advanced Solid Tumor resistant HER inhibitor (Pan) Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) L755P were resistant to Vizimpro (dacomitinib) in culture (PMID: 31588020). 31588020
ERBB2 L755P 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) L755P in culture (PMID: 31588020). 31588020
ERBB2 L755P Advanced Solid Tumor resistant HER2 Inhibitor AEE788 Preclinical Actionable In a preclinical study, transformed cell lines expressing ERBB2 (HER2) L755P demonstrated resistance when treated with AEE788 in culture (PMID: 22046346). 22046346
Clinical Trial Phase Therapies Title Recruitment Status
NCT04209465 Phase I BDTX-189 A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors. Recruiting
NCT02673398 Phase II Neratinib Neratinib in Treating Older Patients With Locally Advanced or Metastatic HER2-Positive Breast Cancer Active, not recruiting