Molecular Profile Detail

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Profile Name ERBB2 V777L
Gene Variant Detail

ERBB2 V777L (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 V777L colorectal cancer resistant Cetuximab Preclinical - Pdx Actionable In a preclinical study, human colorectal cancer cells over expressing ERBB2 (HER2) V777L were resistant to Erbitux (cetuximab) in culture and in patient-derived xenograft models (PMID: 26243863). 26243863
ERBB2 V777L Advanced Solid Tumor conflicting Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) V777L were resistant to Tykerb (lapatinib) in culture (PMID: 31588020). 31588020
ERBB2 V777L Advanced Solid Tumor conflicting Lapatinib Preclinical Actionable In a preclinical study, Tykerb (lapatinib) inhibited proliferation of transformed cell lines expressing ERBB2 (HER2) V777L in culture (PMID: 22046346). 22046346
ERBB2 V777L 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) V777L in culture (PMID: 31588020). 31588020
ERBB2 V777L Advanced Solid Tumor sensitive HER2 Inhibitor Pyrotinib Preclinical - Cell culture Actionable In a preclinical study, Pyrotinib inhibited survival of transformed cells expressing ERBB2 (HER2) V777L in culture (PMID: 31588020). 31588020
ERBB2 V777L 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) V777L in culture (PMID: 31588020). 31588020
ERBB2 V777L Advanced Solid Tumor sensitive Nazartinib Preclinical - Cell culture Actionable In a preclinical study, Nazartinib (EGF816) inhibited survival of transformed cells expressing ERBB2 (HER2) V777L in culture (PMID: 31588020). 31588020
ERBB2 V777L endometrial cancer predicted - sensitive 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 6.9 months in a patient with endometrial cancer harboring ERBB2 (HER2) V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L 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 in one patient, and progressive disease in 4 patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L Advanced Solid Tumor sensitive HER2 Inhibitor Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, Imbruvica (ibrutinib) inhibited survival of transformed cells expressing ERBB2 (HER2) V777L in culture (PMID: 31588020). 31588020
ERBB2 V777L urinary bladder cancer predicted - sensitive 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 6.9 months in a patients with bladder cancer harboring ERBB2 (HER2) V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L biliary tract cancer conflicting 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 one patient, and progressive disease with a progression-free survival of 0.8 months in another patient with biliary tract cancer harboring ERBB2 (HER2) V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L colon cancer sensitive HER2 Inhibitor Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited colony formation in transformed mouse colon epithelial cells over expressing ERBB2 (HER2) V777L in culture (PMID: 26243863). 26243863
ERBB2 V777L colorectal cancer sensitive HER2 Inhibitor Neratinib + Trastuzumab Preclinical - Cell line xenograft Actionable In a preclinical study, Herceptin (trastuzumab) and Nerlynx (neratinib) combination treatment inhibited growth of colorectal cancer cells over expressing ERBB2 (HER2) V777L in culture and suppressed tumor growth in cell line xenograft models (PMID: 26243863). 26243863
ERBB2 V777L colorectal cancer conflicting 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 1.4 months in a patient with colorectal cancer harboring ERBB2 (HER2) V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L colorectal cancer conflicting HER2 Inhibitor Neratinib Preclinical - Cell line xenograft Actionable In a preclinical study, Nerlynx (neratinib) inhibited growth of colorectal cancer cells over expressing ERBB2 (HER2) V777L in culture and suppressed tumor growth in cell line xenograft models (PMID: 26243863). 26243863
ERBB2 V777L breast cancer predicted - sensitive Trastuzumab + Vinorelbine Case Reports/Case Series Actionable In a clinical case study, the combination of Navelbine (vinorelbine) and Herceptin (trastuzumab) resulted in a partial response with tumor regression in a breast cancer patient harboring ERBB2 (HER2) V777L (PMID: 31118664). 31118664
ERBB2 V777L colorectal cancer sensitive HER inhibitor (Pan) Afatinib Preclinical Actionable In a preclinical study, Gilotrif (afatinib) inhibited growth of colorectal cancer cells over expressing ERBB2 (HER2) V777L in culture (PMID: 26243863). 26243863
ERBB2 V777L breast cancer sensitive Trastuzumab Preclinical Actionable In a preclinical study, transformed human breast cell lines expressing ERBB2 V777L reverted to normal morphology in culture upon Herceptin (trastuzumab) treatment (PMID: 23220880). 23220880
ERBB2 V777L 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) V777L in culture (PMID: 31588020). 31588020
ERBB2 V777L breast cancer sensitive HER2 Inhibitor Neratinib Preclinical Actionable In a preclinical study, transformed human breast cell lines expressing ERBB2 (HER2) V777L demonstrated growth inhibition when treated with Nerlynx (neratinib) (PMID: 23220880). 23220880
ERBB2 V777L colon cancer resistant Trastuzumab Preclinical Actionable In a preclinical study, transformed mouse colon epithelial cells over expressing ERBB2 (HER2) V777L were resistant to Herceptin (trastuzumab) in culture (PMID: 26243863). 26243863
ERBB2 V777L lung adenocarcinoma predicted - sensitive HER inhibitor (Pan) Afatinib Case Reports/Case Series Actionable In a retrospective study, Gilotrif (afatinib) treatment resulted in a partial response in a patient with lung adenocarcinoma harboring ERBB2 (HER2) V777L (PMID: 32162827). 32162827
ERBB2 V777L Advanced Solid Tumor sensitive HER2 Inhibitor AEE788 Preclinical Actionable In a preclinical study, transformed cell lines expressing ERBB2 (HER2) V777L demonstrated growth inhibition when treated with AEE788 in culture (PMID: 22046346). 22046346
ERBB2 V777L breast cancer sensitive Lapatinib Preclinical Actionable In a preclinical study, transformed human breast cell lines expressing ERBB2 V777L demonstrated growth inhibition when treated with Tykerb (lapatinib) (PMID: 23220880). 23220880
ERBB2 V777L gastroesophageal junction adenocarcinoma 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 1.1 months in a patient with gastroesophageal cancer harboring ERBB2 (HER2) V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L 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) V777L in culture (PMID: 31588020). 31588020
ERBB2 V777L colorectal cancer resistant Panitumumab Preclinical Actionable In a preclinical study, colorectal cancer cells over expressing ERBB2 (HER2) V777L were resistant to Vectibix (panitumumab) in culture (PMID: 26243863). 26243863
ERBB2 V777L Advanced Solid Tumor resistant HER2 Inhibitor Sapitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 (HER2) V777L were resistant to Sapitinib (AZD8931) in culture (PMID: 31588020). 31588020
ERBB2 V777L Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited survival of transformed cells expressing ERBB2 (HER2) V777L in culture (PMID: 31588020). 31588020
Clinical Trial Phase Therapies Title Recruitment Status
NCT02675829 Phase II Ado-trastuzumab emtansine Trial of Ado-Trastuzumab Emtansine for Patients With HER2 Amplified or Mutant Cancers Active, not recruiting
NCT02673398 Phase II Neratinib Neratinib in Treating Older Patients With Locally Advanced or Metastatic 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
NCT04209465 Phase I BDTX-189 A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors. Recruiting