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Gene ERBB2
Variant Y772_A775dup
Impact List duplication
Protein Effect gain of function
Gene Variant Descriptions ERBB2 (HER2) Y772_A775dup (also referred to as A775_G776insYVMA, M774_A775insAYVM, and E770delinsEAYVM) indicates the insertion of 4 duplicate amino acids, tyrosine (Y)-772 through alanine (A)-775, in the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). Y772_A775dup results in the constitutive phosphorylation of Erbb2 (Her2), activation of downstream signaling, is transforming in cell culture (PMID: 17311002, PMID: 31588020), and confers resistance to selected tyrosine kinase inhibitors (PMID: 31588020).
Associated Drug Resistance Y

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Transcript NM_004448
gDNA chr17:g.39724732_39724743
cDNA c.2314_2325
Protein p.Y772_A775
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001289937 chr17:g.39724732_39724743 c.2314_2325 p.Y772_A775 RefSeq GRCh38/hg38
NM_004448 chr17:g.39724732_39724743 c.2314_2325 p.Y772_A775 RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 Y772_A775dup Advanced Solid Tumor conflicting 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 Advanced Solid Tumor conflicting 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 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 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 sensitive 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 sensitive 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 lung adenocarcinoma predicted - sensitive 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 sensitive 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 urinary bladder cancer predicted - resistant 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 breast cancer sensitive 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 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 Advanced Solid Tumor resistant 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 breast cancer sensitive 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 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 non-small cell carcinoma no benefit 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 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 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 resistant 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 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 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 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 lung cancer sensitive 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 adenocarcinoma no benefit 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 lung adenocarcinoma no benefit 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 Her2-receptor negative breast cancer predicted - sensitive 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 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
ERBB2 Y772_A775dup lung non-small cell carcinoma predicted - sensitive 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 conflicting 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 Advanced Solid Tumor conflicting 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 resistant 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 Advanced Solid Tumor resistant 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 lung non-small cell carcinoma no benefit 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 cancer sensitive 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 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 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 resistant 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 lung non-small cell carcinoma predicted - sensitive 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 non-small cell carcinoma predicted - sensitive 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 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 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 ERBB2 C805S Advanced Solid Tumor resistant Neratinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing ERBB2 (HER2) Y772_A775dup (also referred to as A775_G776insYVMA) and ERBB2 (HER2) C805S demonstrated resistance to Nerlynx (neratinib) in culture (PMID: 28363995). 28363995
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S were resistant to Tykerb (lapatinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S were resistant to Tagrisso (osimertinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S 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) and an acquired ERBB2 (HER2) C805S in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Poziotinib Preclinical - Cell culture Actionable In a preclinical study, ERBB2 (HER2) C805S was identified as a secondary mutation in transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) that acquired resistance to Poziotinib (HM781-36B) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S 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) and an acquired ERBB2 (HER2) C805S in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant AZ5104 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S were resistant to AZ5104 in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing ERBB2 (HER2) Y772_A775dup (also referred to as A775_G776insYVMA) and ERBB2 (HER2) C805S demonstrated resistance to Gilotrif (afatinib) in culture (PMID: 28363995). 28363995
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing ERBB2 (HER2) C805S and ERBB2 (HER2) Y772_A775dup (also referred to as A775_G776insYVMA) demonstrated resistance to Vizimpro (dacomitinib) in culture (PMID: 28363995). 28363995
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S were resistant to Tarceva (erlotinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Tucatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S were resistant to Tukysa (tucatinib) in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 C805S Advanced Solid Tumor resistant Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) Y772_A775dup (reported as A775_G776insYVMA) and an acquired ERBB2 (HER2) C805S were resistant to Pyrotinib in culture (PMID: 30527195). 30527195
ERBB2 Y772_A775dup ERBB2 amp Her2-receptor positive breast cancer predicted - sensitive Neratinib Case Reports/Case Series Actionable In a clinical study, Nerlynx (neratinib) treatment resulted in partial response in 2 of 6 and disease stabilization in 4 of 6 breast cancer patients with ERBB2 (HER2) amplification and an ERBB2 (HER2) mutation, including stable disease in a patient harboring ERBB2 (HER2) Y772_A775dup (PMID: 30301790). 30301790
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 exon 20 ins lung non-small cell carcinoma predicted - sensitive Afatinib Case Reports/Case Series Actionable In a clinical study, targeted therapy with Gilotrif (afatinib) or Herceptin (trastuzumab) resulted in an objective response rate of 44% (4/9) in non-small cell lung carcinoma patients harboring ERBB2 (HER2) mutations that progressed during previous therapies, all four responders harbored ERBB2 (HER2) exon 20 insertions (PMID: 28167203). 28167203
ERBB2 exon 20 ins lung non-small cell carcinoma predicted - sensitive Docetaxel + Trastuzumab Case Reports/Case Series Actionable In a clinical study, treatment with the combination of Herceptin (trastuzumab) and Taxotere (docetaxel) in a non-small cell lung cancer patient harboring an ERBB2 exon 20 insertion resulted in a partial response (PMID: 23610105). 23610105
ERBB2 exon 20 ins Advanced Solid Tumor sensitive AP32788 Preclinical - Pdx & cell culture Actionable In a preclinical study, AP32788 inhibited growth of transformed cell lines over expressing ERBB2 (HER2) exon 20 insertions in culture, and induced tumor regression in PDX models (AACR, Cancer Res: April 2016; Volume 57, Abstract #2644). detail...
ERBB2 exon 20 ins Her2-receptor negative breast cancer predicted - sensitive Neratinib Case Reports/Case Series Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in complete response in 1, partial response in 1, and stable disease in 3 of the 5 patients with Erbb2 (Her2)-receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) exon 20 insertion mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 exon 20 ins lung adenocarcinoma predicted - sensitive Dacomitinib Phase II Actionable In a Phase II trial, Vizimpro (dacomitinib) treatment resulted in an overall response rate of 25% (3/26) in patients with lung adenocarcinoma harboring ERBB2 (HER2) exon 20 mutations, including exon 20 insertions, indels, and missense mutations (23, 2, 1, respectively) (PMID: 25899785; NCT00818441). 25899785
ERBB2 exon 20 ins lung adenocarcinoma predicted - sensitive Afatinib Case Reports/Case Series Actionable In a clinical study, treatment with pulse Gilotrif (afatinib) resulted in an objective response rate of 33.3% (1/3) in lung adenocarcinoma patients with ERBB2 (HER2) exon 20 insertion mutations (PMID: 26964772). 26964772
ERBB2 exon 20 ins lung non-small cell carcinoma predicted - sensitive Trastuzumab Case Reports/Case Series Actionable In a clinical study, targeted therapy with Gilotrif (afatinib) or Herceptin (trastuzumab) resulted in an objective response rate of 44% (4/9) in non-small cell lung carcinoma patients harboring ERBB2 (HER2) mutations that progressed during previous therapies, all four responders harbored ERBB2 (HER2) exon 20 insertions (PMID: 28167203). 28167203
ERBB2 exon 20 ins lung non-small cell carcinoma predicted - sensitive Trastuzumab Case Reports/Case Series Actionable In a clinical study, Herceptin (trastuzumab) treatment in a non-small cell lung cancer patient harboring an ERBB2 exon 20 insertion resulted in a partial response (PMID: 23610105). 23610105
ERBB2 exon 20 ins lung non-small cell carcinoma predicted - sensitive Carboplatin + Paclitaxel + Trastuzumab Case Reports/Case Series Actionable In a clinical study, treatment with the combination of Herceptin (trastuzumab), Paraplatin (carboplatin), and Taxol (paclitaxel) in non-small cell lung cancer patients harboring an ERBB2 exon 20 insertion (n=2) resulted in a partial response in one patient and stable disease in the other patient (PMID: 23610105). 23610105
ERBB2 exon 20 ins lung non-small cell carcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease in 10 and progressive disease in 5 of the 15 patients with non-small cell lung cancer harboring ERBB2 (HER2) exon 20 insertion mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 exon 20 ins lung non-small cell carcinoma predicted - sensitive Trastuzumab + Vinorelbine Case Reports/Case Series Actionable In a clinical study, treatment with the combination of Herceptin (trastuzumab) and Navelbine (vinorelbine) in non-small cell lung cancer patients harboring an ERBB2 exon 20 insertion (n=8) resulted in a partial response in 5 patients and stable disease in 2 patients (PMID: 23610105). 23610105
ERBB2 exon20 lung non-small cell carcinoma predicted - sensitive Pyrotinib Phase II Actionable In a Phase II trial, non-small cell lung cancer patients harboring an ERBB2 exon 20 mutation demonstrated an objective response rate of 53.3% (8/15) and a median progression-free survival of 6.4 months when treated with Pyrotinib (PMID: 30596880; NCT02535507). 30596880
ERBB2 exon20 lung non-small cell carcinoma predicted - sensitive Pyrotinib Phase I Actionable In a Phase II trial, Pyrotinib treatment resulted in an objective response rate of 31.7% (19/60) in non-small cell lung cancer patients harboring ERBB2 (HER2) exon 20 mutations, with a median duration of response of 7.0 months and a median progression-free survival of 6.8 months (J Clin Oncol 37, 2019 (suppl; abstr 9089); NCT02834936). detail...
ERBB2 mutant lung non-small cell carcinoma predicted - sensitive Trastuzumab + Vinorelbine Case Reports/Case Series Actionable In a clinical study, treatment with Herceptin (trastuzumab) in combination with chemotherapy resulted in an objective response rate of 67% (4/6) in non-small cell lung carcinoma patients harboring ERBB2 (HER2) mutations that progressed during previous therapies (PMID: 28167203). 28167203
ERBB2 mutant biliary tract cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in an objective response rate at 8 weeks of 22.2% (2/9), a clinical benefit rate of 33.3% (3/9), and a median progression-free survival of 2.8 months in patients with biliary tract cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant Her2-receptor negative breast cancer sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in an object response rate of 24% (6/25), a clinical benefit rate of 40% (10/25), and a median progression-free survival of 3.5 months in patients with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant lung non-small cell carcinoma no benefit Trastuzumab Guideline Actionable Herceptin (trastuzumab) is not recommended as a monotherapy in guidelines for non-small cell lung cancer patients with ERBB2 mutations (NCCN.org). detail...
ERBB2 mutant lung adenocarcinoma sensitive Afatinib Phase II Actionable In a Phase II trial, treatment with Gilotrif (afatinib) resulted in objective response in 3 lung adenocarcinoma patients harboring ERBB2 (HER2) mutations (PMID: 22325357). 22325357
ERBB2 mutant breast cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial, Nerlynx (neratinib) demonstrated activity in metastatic breast cancer patients harboring ERBB2 (HER2) mutations, with treatment resulting in a clinical benefit rate of 31% (5/16; 1 complete response, 1 partial response, and 3 patients achieving stable disease for 24 weeks or more) and a median progression-free survival of 16 weeks (PMID: 28679771). 28679771
ERBB2 mutant endometrial cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in no objective response, a clinical benefit rate of 28.6% (2/7), and a median progression-free survival of 2.6 months in patients with endometrial cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant colorectal cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in no objective response, a clinical benefit rate of 8.3% (1/12), and a median progression-free survival of 1.8 months in patients with colorectal cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant invasive bladder transitional cell carcinoma predicted - sensitive Cisplatin + Gemcitabine + Sorafenib Phase II Actionable In a Phase II trial, ERBB2 (HER2) mutations were only detected in patients with muscle-invasive urothelial bladder cancer that responded to Nexavar (sorafenib), Platinol (cisplatin) and Gemzar (gemcitabine) combination therapy (J Clin Oncol 35, 2017 (suppl 6S; abstract 345)). detail...
ERBB2 mutant Her2-receptor positive breast cancer sensitive Neratinib Phase II Actionable In a Phase II trial, Nerlynx (neratinib) treatment resulted in complete response in 12.5% (3/24) and partial response in 20.8% (5/24) of ERBB2 (HER2) mutant but not amplified breast cancer patients (Cancer Res 2017;77(4 Suppl):Abstract nr PD2-08). detail...
ERBB2 mutant ovarian cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in no objective response, no clinical benefit, and a median progression-free survival of 2.1 months in patients with ovarian cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant cervical cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in an objective response rate of 20% (1/5), a clinical benefit rate of 60% (3/5), and a median progression-free survival of 20.1 months in patients with cervical cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant gastroesophageal junction adenocarcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in no objective response, a clinical benefit rate of 20% (1/5), and a median progression-free survival of 1.7 months in patients with gastroesophageal cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant lung non-small cell carcinoma sensitive Ado-trastuzumab emtansine Guideline Actionable Kadcyla (trastuzumab emtansine) is included in guidelines for non-small cell lung cancer patients with ERBB2 (HER2) mutations (NCCN.org). detail...
ERBB2 mutant lung non-small cell carcinoma sensitive Pyrotinib Phase II Actionable In a Phase II trial, Pyrotinib treatment in non-small cell lung cancer patients harboring an ERBB2 (HER2) mutation resulted in a partial response in 54.5% (6/11) of patients and stable disease in 27.3% (3/11) of patients, and a PFS of 6.2 months (Journal of Thoracic Oncology, Vol. 12, Issue 1, S359). detail...
ERBB2 mutant lung cancer sensitive Neratinib Phase I Actionable In a Phase I clinical trial, Nerlynx (neratinib) administered with Torisel (temsirolimus) was tolerable and demonstrated antitumor activity in ERBB2 (HER2)-mutant non-small-cell lung cancer (PMID: 24323026). 24323026
ERBB2 mutant lung non-small cell carcinoma sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in an objective response rate of 3.8% (1/26), a clinical benefit rate of 42.3% (11/26), and a median progression-free survival of 5.5 months in patients with non-small cell lung cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant lung non-small cell carcinoma sensitive Neratinib Phase I Actionable In a Phase I study, Nerlynx (neratinib) administered with temsirolimus was tolerable and demonstrated antitumor activity in ERBB2-mutant non-small-cell lung cancer (PMID: 24323026). 24323026
ERBB2 mutant lung squamous cell carcinoma predicted - sensitive Afatinib Phase III Actionable In a Phase III trial (LUX-Lung 8), secondary analysis demonstrated favorable outcomes with Gilotrif (afatinib) treatment compared to Tarceva (erlotinib) in lung squamous cell carcinoma patients with ERBB (HER) family mutations, and ERBB2 (HER2) mutations predicted an OS (HR=0.06, p=0.02) and PFS (HR=0.06, p=0.02) benefit for Gilotrif (afatinib) over Tarceva (erlotinib) treatment (PMID: 29902295; NCT01523587). 29902295
ERBB2 mutant urinary bladder cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in no objective response, a clinical benefit rate of 18.8% (3/16), and a median progression-free survival of 1.8 months in patients with bladder cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant lung non-small cell carcinoma sensitive AV-412 Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring an ERBB2 (HER2) mutation demonstrated sensitivity to AV-412, resulting in decreased phosphorylation of Erbb2, Akt, and Erk (PMID: 19459856). 19459856
ERBB2 mutant lung non-small cell carcinoma no benefit Afatinib Guideline Actionable Gilotrif (afatinib) is not recommended as a monotherapy in guidelines for non-small cell lung cancer patients with ERBB2 mutations (NCCN.org). detail...
ERBB2 act mut estrogen-receptor positive breast cancer predicted - sensitive Vistusertib Phase I Actionable In a Phase I trial, Vistusertib (AZD2014) demonstrated safety and preliminary efficacy in patients with advanced solid tumors, including a patient with ER-positive breast cancer harboring an ERBB2 activating mutation (PMID: 25805799). 25805799
ERBB2 act mut lung non-small cell carcinoma predicted - sensitive Pertuzumab + Trastuzumab Phase II Actionable In a Phase II trial (MyPathway), Herceptin (trastuzumab) and Perjeta (pertuzumab) combination treatment resulted in partial response in 21% (3/14) and stable disease lasting over 120 days in 21% (3/14) of patients with non-small cell lung cancer harboring ERBB2 (HER2) activating mutations but not amplification or overexpression (PMID: 29320312; NCT02091141). 29320312
ERBB2 act mut breast cancer sensitive Neratinib Phase II Actionable In a Phase II clinical trial, Nerlynx (neratinib) treatment resulted in clinical benefit in 36% (5/14) of metastatic breast cancer patients harboring ERBB2 (HER2) activating mutations, with 1 complete response, 1 partial response, and 2 patients achieving stable disease for greater than 6 months, and a median progression-free survival of 5 months (J Clin Oncol 34, 2016 (suppl; abstr 516)). detail...
ERBB2 act mut Advanced Solid Tumor sensitive AEE788 Preclinical Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) activation loop mutations demonstrated sensitivity to AEE788 in culture (PMID: 22046346). 22046346
ERBB2 act mut lung non-small cell carcinoma decreased response Nivolumab Clinical Study - Cohort Actionable In a clinical study, immunotherapies including Tecentriq (atezolizumab) (n=5), Opdivo (nivolumab) (n=17), Keytruda (pembrolizumab) (n=36), and Camrelizumab (SHR-1210) (n=20) resulted in significantly shorter median progression-free survival (51.0 vs 70.5 days, HR=2.47, p=0.0037) in non-small cell lung cancer patients harboring EGFR (n=7) or ERBB2 (HER2) (n=7) activating mutations compared to wild-type patients (PMID: 31085721). 31085721
ERBB2 act mut lung adenocarcinoma sensitive Trastuzumab deruxtecan Phase II Actionable In a Phase II trial (DESTINY-Lung01), Enhertu (trastuzumab deruxtecan) treatment resulted in an objective response rate of 61.9% (26/42) and a median progression free survival of 14 months in patients with metastatic non-small cell lung carcinoma harboring ERBB2 activating mutations (J Clin Oncol 38: 2020 (suppl; abstr 9504); NCT03505710). detail...
ERBB2 act mut lung non-small cell carcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a retrospective analysis, activating ERBB2 (HER2) mutations were identified in 3 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). 31839416
ERBB2 act mut biliary tract cancer predicted - sensitive Pertuzumab + Trastuzumab Case Reports/Case Series Actionable In a Phase II trial (MyPathway), Herceptin (trastuzumab) and Perjeta (pertuzumab) combination treatment resulted in an objective response in a patient with biliary cancer harboring an ERBB2 (HER2) activating mutation, but no amplification or overexpression (PMID: 29320312; NCT02091141). 29320312
ERBB2 act mut lung non-small cell carcinoma decreased response Pembrolizumab Clinical Study - Cohort Actionable In a clinical study, immunotherapies including Tecentriq (atezolizumab) (n=5), Opdivo (nivolumab) (n=17), Keytruda (pembrolizumab) (n=36), and Camrelizumab (SHR-1210) (n=20) resulted in significantly shorter median progression-free survival (51.0 vs 70.5 days, HR=2.47, p=0.0037) in non-small cell lung cancer patients harboring EGFR (n=7) or ERBB2 (HER2) (n=7) activating mutations compared to wild-type patients (PMID: 31085721). 31085721
ERBB2 act mut lung adenocarcinoma predicted - sensitive Ado-trastuzumab emtansine Phase II Actionable In a Phase II trial, treatment with Kadcyla (trastuzumab emtansine) resulted in best overall response rates of 44% (8/18) and 39% (7/18) partial response and stable disease, respectively, and median progression-free survival of 5 months in patients with lung adenocarcinoma harboring ERBB2 (HER2) activating mutations (PMID: 29989854; NCT02675829). 29989854
ERBB2 act mut lung non-small cell carcinoma decreased response Camrelizumab Clinical Study - Cohort Actionable In a clinical study, immunotherapies including Tecentriq (atezolizumab) (n=5), Opdivo (nivolumab) (n=17), Keytruda (pembrolizumab) (n=36), and Camrelizumab (SHR-1210) (n=20) resulted in significantly shorter median progression-free survival (51.0 vs 70.5 days, HR=2.47, p=0.0037) in non-small cell lung cancer patients harboring EGFR (n=7) or ERBB2 (HER2) (n=7) activating mutations compared to wild-type patients (PMID: 31085721). 31085721
ERBB2 act mut lung non-small cell carcinoma decreased response Atezolizumab Clinical Study - Cohort Actionable In a clinical study, immunotherapies including Tecentriq (atezolizumab) (n=5), Opdivo (nivolumab) (n=17), Keytruda (pembrolizumab) (n=36), and Camrelizumab (SHR-1210) (n=20) resulted in significantly shorter median progression-free survival (51.0 vs 70.5 days, HR=2.47, p=0.0037) in non-small cell lung cancer patients harboring EGFR (n=7) or ERBB2 (HER2) (n=7) activating mutations compared to wild-type patients (PMID: 31085721). 31085721
ERBB2 act mut Advanced Solid Tumor predicted - sensitive Pertuzumab + Trastuzumab Phase II Actionable In a Phase II trial (MyPathway), Herceptin (trastuzumab) and Perjeta (pertuzumab) combination treatment resulted in objective response in 11% (4/36) of patients with advanced solid tumors harboring ERBB2 (HER2) activating mutations but not amplification or overexpression (PMID: 29320312; NCT02091141). 29320312