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Profile Name ERBB2 Y772_A775dup
Gene Variant Detail

ERBB2 Y772_A775dup (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 Y772_A775dup Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Tagrisso (osimertinib) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) were resistant to Tagrisso (osimertinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor resistant HER2 Inhibitor Tucatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) were resistant to Tukysa (tucatinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor resistant HER inhibitor (Pan) Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Vizimpro (dacomitinib) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor resistant HER inhibitor (Pan) Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) demonstrated decreased response to Vizimpro (dacomitinib) compared to Poziotinib (HM781-36B) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor predicted - sensitive Luminespib Preclinical - Cell culture Actionable In a preclinical study, Luminespib (AUY922) inhibited growth of transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as reported as A775_G776insYVMA) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup lung cancer sensitive HER inhibitor (Pan) Poziotinib Preclinical Actionable In a preclinical study, Poziotinib (HM781-36B) induced regression of lung tumors in mouse models harboring ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA), with no signs of progression at 12 weeks (PMID: 29686424). 29686424
ERBB2 Y772_A775dup lung cancer no benefit Gefitinib Preclinical Actionable In a preclinical study, bronchial epithelial cells expressing ERBB2 (HER2) Y772_A775dup (also referred to as A775_G776insYVMA) did not demonstrate sensitivity to Iressa (gefitinib) in culture (PMID: 26545934). 26545934
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) were resistant to Tarceva (erlotinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor resistant HER2 Inhibitor Tarloxotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Tarloxotinib (TRLX) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor predicted - sensitive Ganetespib Preclinical - Cell culture Actionable In a preclinical study, Ganetespib inhibited growth of transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as reported as A775_G776insYVMA) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup lung adenocarcinoma no benefit 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, ORR (0%, 0/14), DCR (35.7%, 5/14), and median progression-free survival (1.2 mo) were significantly lower in patients with Y772_A775dup than those with other exon 20 insertions (40%, 4/10; 100%, 10/10; 7.6 mo) or missense mutations (13%, 1/8; 75%, 6/8; 3.6 mo) (PMID: 32162827). 32162827
ERBB2 Y772_A775dup lung adenocarcinoma no benefit HER inhibitor (Pan) Afatinib Case Reports/Case Series Actionable In a clinical study, a lung adenocarcinoma patient harboring ERBB2 Y772_A775dup (also referred to as A775_G776insYVMA and E740_A741insAYVM) achieved a partial response for 5 months following treatment with pulse Gilotrif (afatinib), however, a second patient harboring ERBB2 Y772_A775dup treated with pulse Gilotrif (afatinib) demonstrated progressive disease (PMID: 26964772). 26964772
ERBB2 Y772_A775dup Advanced Solid Tumor resistant HER inhibitor (Pan) Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) demonstrated decreased response to Gilotrif (afatinib) compared to Poziotinib (HM781-36B) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor resistant HER inhibitor (Pan) Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Gilotrif (afatinib) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup lung non-small cell carcinoma predicted - sensitive HER inhibitor (Pan) Poziotinib Phase II Actionable In a Phase II trial, Poziotinib (HM781-36B) treatment resulted in a confirmed objective response rate of 42% (5/12) in patients with non-small cell lung cancer harboring ERBB2 (HER2) Y772_A775dup (n=9) or ERBB2 (HER2) G778_P780dup (n=3), with a median progression-free survival of 5.6 months (PMID: 31588020; NCT03066206). 31588020
ERBB2 Y772_A775dup 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 33% (1/3) in non-small cell lung cancer patients harboring ERBB2 (HER2) Y772_A775dup (reported as (A775_G776insYVMA) (PMID: 30527195). 30527195
ERBB2 Y772_A775dup 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) Y772_A775dup (also referred to as A775_G776insYVMA) in culture (PMID: 26545934). 26545934
ERBB2 Y772_A775dup lung non-small cell carcinoma predicted - sensitive HER2 Inhibitor Pyrotinib Phase II Actionable In a Phase II trial, Pyrotinib treatment resulted in an objective response rate of 27.3% (12/44) in non-small cell lung cancer patients harboring ERBB2 (HER2) Y772_A775dup (also reported as A775_G776insYVMA or M774_A775insAYVM) who had received prior platinum-based chemotherapy (PMID: 32614698; NCT02834936). 32614698
ERBB2 Y772_A775dup Advanced Solid Tumor resistant AZ5104 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) were resistant to AZ5104 in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup lung non-small cell carcinoma no benefit HER2 Inhibitor Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease in 5 patients and progressive disease in 4 patients with non-small cell lung cancer harboring ERBB2 (HER2) Y772_A775dup (PMID: 29420467; NCT01953926). 29420467
ERBB2 Y772_A775dup 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) Y772_A775dup in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor sensitive HER inhibitor (Pan) Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited ERBB2 (HER2) phosphorylation and growth of a transformed cell line expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) in culture (PMID: 29686424). 29686424
ERBB2 Y772_A775dup Advanced Solid Tumor resistant HER2 Inhibitor Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Imbruvica (ibrutinib) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup urinary bladder cancer predicted - resistant HER2 Inhibitor Neratinib Case Reports/Case Series Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.7 months in a patients with bladder cancer harboring ERBB2 (HER2) Y722_A775dup (PMID: 29420467; NCT01953926). 29420467
ERBB2 Y772_A775dup lung adenocarcinoma predicted - sensitive HER inhibitor (Pan) Poziotinib Case Reports/Case Series Actionable In a Phase II trial, Poziotinib (HM781-36B) treatment resulted in one partial response, stable disease in one patient, and progressive disease in three patients with lung adenocarcinoma harboring ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) (PMID: 30149884; NCT02979821). 30149884
ERBB2 Y772_A775dup lung non-small cell carcinoma predicted - sensitive HER inhibitor (Pan) Afatinib Clinical Study Actionable In a retrospective analysis, Gilotrif (afatinib) treatment resulted in an objective response rate of 16% (5/31) in non-small cell lung cancer patients harboring ERBB2 (HER2) Y772_A775dup (reported as (A775_G776insYVMA) (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Tykerb (lapatinib) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) were resistant to Tykerb (lapatinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup breast cancer sensitive HER inhibitor (Pan) Poziotinib Preclinical - Cell culture Actionable In a preclinical study, Poziotinib (HM781-36B) inhibited viability of breast cancer cells expressing ERBB2 (HER2) Y772_A775dup in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor conflicting HER2 Inhibitor Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, Pyrotinib inhibited growth of transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor conflicting HER2 Inhibitor Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y722_A755dup were resistant to Pyrotinib in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup 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% (0/13) in non-small cell lung cancer patients harboring ERBB2 (HER2) Y772_A775dup (reported as (A775_G776insYVMA) (PMID: 30527195). 30527195
ERBB2 Y772_A775dup lung non-small cell carcinoma sensitive HER inhibitor (Pan) Ado-trastuzumab emtansine + Poziotinib Preclinical - Pdx Actionable In a preclinical study, Poziotinib (HM781-36B) and Kadcyla (ado-trastuzumab emtansine) combination treatment resulted in sustained tumor regression in patient-derived xenograft models of non-small cell lung cancer harboring ERBB2 (HER2) Y772_A775dup (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor conflicting HER2 Inhibitor Neratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Nerlynx (neratinib) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup 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) Y772_A775dup (also referred to as ERBB2 A775_G776insYVMA) in culture (PMID: 28363995). 28363995
ERBB2 Y772_A775dup 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) Y772_A775dup in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup Advanced Solid Tumor resistant HER2 Inhibitor Sapitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Sapitinib (AZD8931) in culture (PMID: 31588020). 31588020
ERBB2 Y772_A775dup 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 complete response in one patient, and stable disease in 2 patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) Y772_A775dup (PMID: 29420467; NCT01953926). 29420467
ERBB2 Y772_A775dup 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) Y772_A775dup (reported as (A775_G776insYVMA) (PMID: 30527195). 30527195
ERBB2 Y772_A775dup Advanced Solid Tumor resistant Nazartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup were resistant to Nazartinib (EGF816) in culture (PMID: 31588020). 31588020
Clinical Trial Phase Therapies Title Recruitment Status
NCT02673398 Phase II Neratinib Neratinib in Treating Older Patients With Stage IV HER2-Positive Breast Cancer Active, not recruiting
NCT03066206 Phase II Poziotinib Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC Recruiting
NCT02675829 Phase II Ado-trastuzumab emtansine Trial of Ado-Trastuzumab Emtansine for Patients With HER2 Amplified or Mutant Cancers Active, not recruiting