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Profile Name ERBB2 G776delinsVC
Gene Variant Detail

ERBB2 G776delinsVC (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 G776delinsVC Advanced Solid Tumor resistant HER2 Inhibitor Sapitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC were resistant to Sapitinib (AZD8931) in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC lung non-small cell carcinoma no benefit HER inhibitor (Pan) Dacomitinib Clinical Study Actionable In a retrospective analysis, Vizimpro (dacomitinib) treatment resulted in an objective response rate of 0% (0/2) in non-small cell lung cancer patients harboring ERBB2 (HER2) G776delinsVC (PMID: 30527195). 30527195
ERBB2 G776delinsVC lung adenocarcinoma predicted - sensitive 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, and a subset of patients specifically harboring ERBB2 (HER2) G776delinsVC had a 100% (2/2) partial response rate (PMID: 29989854; NCT02675829). 29989854
ERBB2 G776delinsVC Advanced Solid Tumor resistant Nazartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC were resistant to Nazartinib (EGF816) in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC 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 G776delinsVC demonstrated a partial response and an ongoing progression-free survival when treated with Pyrotinib (PMID: 30596880; NCT02535507). 30596880
ERBB2 G776delinsVC Advanced Solid Tumor conflicting HER inhibitor (Pan) Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, Vizimpro (dacomitinib) inhibited growth of transformed cells expressing ERBB2 (HER2) G776delinsVC in culture (PMID: 30527195). 30527195
ERBB2 G776delinsVC Advanced Solid Tumor conflicting HER inhibitor (Pan) Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC were resistant to Vizimpro (dacomitinib) in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC lung non-small cell carcinoma conflicting HER inhibitor (Pan) Afatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gilotrif (afatinib) inhibited proliferation and induced cell-cycle arrest and apoptosis of a non-small cell lung cancer (NSCLC) cell line harboring ERBB2 (HER2) G776delinsVC in culture and inhibited tumor growth in NSCLC cell line xenografts carrying ERBB2 (HER2) G776delinsVC (PMID: 26545934). 26545934
ERBB2 G776delinsVC lung non-small cell carcinoma conflicting HER inhibitor (Pan) Afatinib Clinical Study Actionable In a retrospective analysis, Gilotrif (afatinib) treatment resulted in an objective response rate of 0% (0/3) in non-small cell lung cancer patients harboring ERBB2 (HER2) G776delinsVC (PMID: 30527195). 30527195
ERBB2 G776delinsVC Advanced Solid Tumor resistant HER2 Inhibitor Tarloxotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC were resistant to Tarloxotinib (TRLX) in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC lung non-small cell carcinoma no benefit Lapatinib Clinical Study Actionable In a retrospective analysis, Tykerb (lapatinib) treatment resulted in an objective response rate of 0% (0/1) in non-small cell lung cancer patients harboring ERBB2 (HER2) G776delinsVC (PMID: 30527195). 30527195
ERBB2 G776delinsVC lung adenocarcinoma predicted - sensitive HER inhibitor (Pan) Afatinib Clinical Study - Cohort Actionable In a retrospective study, Gilotrif (afatinib) treatment resulted in an objective response rate (ORR) of 15.6% (5/32) and a disease control rate of 68.8% (22/32) in patients with lung adenocarcinoma harboring ERBB2 (HER2) mutations, patients harboring G776delinsVC (n=5) or G778_P780dup (n=5) achieved longer median progression-free survival (7.6 mo) than those with Y772_A775dup (n=14, 1.2 mo) or missense mutations (n=8, 3.6 mo), with an ORR of 40% (4/10) and a DCR of 100% (10/10) (PMID: 32162827). 32162827
ERBB2 G776delinsVC Advanced Solid Tumor decreased response Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC demonstrated decreased response to Tarceva (erlotinib) compared to Poziotinib (HM781-36B) in culture (PMID: 30527195). 30527195
ERBB2 G776delinsVC breast cancer sensitive HER inhibitor (Pan) Ado-trastuzumab emtansine + Poziotinib Preclinical - Cell culture Actionable In a preclinical study, addition of Poziotinib (HM781-36B) enhanced growth inhibition by Kadcyla (ado-trastuzumab emtansine) treatment in breast cancer cells expressing ERBB2 (HER2) G776delinsVC in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC 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 8.5 months in a patient with non-small cell lung cancer harboring ERBB2 (HER2) G776delinsVC (PMID: 29420467; NCT01953926). 29420467
ERBB2 G776delinsVC Advanced Solid Tumor predicted - sensitive Luminespib Preclinical - Cell culture Actionable In a preclinical study, Luminespib (AUY922) inhibited growth of transformed cells expressing ERBB2 (HER2) G776delinsVC in culture (PMID: 30527195). 30527195
ERBB2 G776delinsVC Advanced Solid Tumor resistant HER2 Inhibitor Tucatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC were resistant to Tukysa (tucatinib) in culture (PMID: 30527195). 30527195
ERBB2 G776delinsVC 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) G776delinsVC in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC Advanced Solid Tumor sensitive HER inhibitor (Pan) Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited growth of a transformed cell line expressing ERBB2 (HER2) G776delinsVC in culture (PMID: 29686424). 29686424
ERBB2 G776delinsVC lung adenocarcinoma predicted - sensitive HER inhibitor (Pan) Poziotinib Case Reports/Case Series Actionable In a Phase II trial, Poziotinib (HM781-36B) treatment resulted in a partial response in one patient and stable disease in another patient with lung adenocarcinoma harboring ERBB2 (HER2) G776delinsVC (PMID: 30149884; NCT02979821). 30149884
ERBB2 G776delinsVC Advanced Solid Tumor conflicting HER2 Inhibitor Neratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC were resistant to Nerlynx (neratinib) in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC Advanced Solid Tumor conflicting HER2 Inhibitor Neratinib Preclinical - Cell culture Actionable In a preclinical study, Nerlynx (neratinib) inhibited growth of transformed cells expressing ERBB2 (HER2) G776delinsVC in culture (PMID: 30527195). 30527195
ERBB2 G776delinsVC Advanced Solid Tumor conflicting HER2 Inhibitor Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC were resistant to Pyrotinib in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC Advanced Solid Tumor conflicting HER2 Inhibitor Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, Pyrotinib inhibited growth of transformed cells expressing ERBB2 (HER2) G776delinsVC in culture (PMID: 30527195). 30527195
ERBB2 G776delinsVC Advanced Solid Tumor resistant HER2 Inhibitor Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC were resistant to Imbruvica (ibrutinib) in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC Advanced Solid Tumor conflicting Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited growth of transformed cells expressing ERBB2 (HER2) G776delinsVC in culture (PMID: 30527195). 30527195
ERBB2 G776delinsVC Advanced Solid Tumor conflicting Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC were resistant to Tagrisso (osimertinib) in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC lung non-small cell carcinoma resistant Gefitinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring ERBB2 (HER2) G776delinsVC demonstrated resistance to treatment with Iressa (gefitinib) in culture (PMID: 26545934). 26545934
ERBB2 G776delinsVC lung non-small cell carcinoma no benefit Erlotinib Clinical Study Actionable In a retrospective analysis, Tarceva (erlotinib) treatment resulted in an objective response rate of 0% (0/1) in non-small cell lung cancer patients harboring ERBB2 (HER2) G776delinsVC (PMID: 30527195). 30527195
ERBB2 G776delinsVC lung cancer sensitive HER inhibitor (Pan) Afatinib Preclinical Actionable In a preclinical study, Gilotrif (afatinib) inhibited Erbb2 (Her2) phosphorylation and downstream signaling in bronchial epithelial cells expressing ERBB2 (HER2) G776delinsVC in culture (PMID: 26545934). 26545934
ERBB2 G776delinsVC Advanced Solid Tumor predicted - sensitive Ganetespib Preclinical - Cell culture Actionable In a preclinical study, Ganetespib inhibited growth of transformed cells expressing ERBB2 (HER2) G776delinsVC in culture (PMID: 30527195). 30527195
ERBB2 G776delinsVC Advanced Solid Tumor conflicting HER inhibitor (Pan) Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited growth of transformed cells expressing ERBB2 (HER2) G776delinsVC in culture (PMID: 30527195). 30527195
ERBB2 G776delinsVC Advanced Solid Tumor conflicting HER inhibitor (Pan) Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC were resistant to Gilotrif (afatinib) in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC breast cancer sensitive HER inhibitor (Pan) Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited Erbb2 (Her2) phosphorylation and viability of breast cancer cells expressing ERBB2 (HER2) G776delinsVC in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC were resistant to Tykerb (lapatinib) in culture (PMID: 30527195). 30527195
ERBB2 G776delinsVC Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) G776delinsVC were resistant to Tykerb (lapatinib) in culture (PMID: 31588020). 31588020
ERBB2 G776delinsVC lung non-small cell carcinoma predicted - sensitive HER inhibitor (Pan) Poziotinib Clinical Study Actionable In a retrospective analysis, Poziotinib (HM781-36B) treatment resulted in an objective response rate of 50% (1/2) in non-small cell lung cancer patients harboring ERBB2 (HER2) G776delinsVC (PMID: 30527195). 30527195
ERBB2 G776delinsVC lung cancer no benefit Gefitinib Preclinical Actionable In a preclinical study, bronchial epithelial cells expressing ERBB2 (HER2) G776delinsVC did not demonstrate sensitivity to Iressa (gefitinib) in culture (PMID: 26545934). 26545934
ERBB2 G776delinsVC Advanced Solid Tumor sensitive AZ5104 Preclinical - Cell culture Actionable In a preclinical study, AZ5104 inhibited growth of transformed cells expressing ERBB2 (HER2) G776delinsVC in culture (PMID: 30527195). 30527195
Clinical Trial Phase Therapies Title Recruitment Status
NCT02673398 Phase II Neratinib Neratinib in Treating Older Patients With Locally Advanced or Metastatic HER2-Positive Breast Cancer Active, not recruiting
NCT02675829 Phase II Ado-trastuzumab emtansine Trial of Ado-Trastuzumab Emtansine for Patients With HER2 Amplified or Mutant Cancers Active, not recruiting