Molecular Profile Detail

Profile Name ERBB2 L755S
Gene Variant Detail

ERBB2 L755S (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 L755S Advanced Solid Tumor sensitive HER2 Inhibitor XL647 Preclinical Actionable In a preclinical study, XL647 inhibited survival of transformed cells over expressing ERBB2 (HER2) L755S in culture (PMID: 18413839). 18413839
ERBB2 L755S non-small cell lung carcinoma predicted - sensitive HER2 Inhibitor Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in partial response with a progression-free survival of 12.7 months in a patient with non-small cell lung cancer harboring ERBB2 (HER2) L755S (PMID: 29420467; NCT01953926). 29420467
ERBB2 L755S breast cancer sensitive HER2 Inhibitor Neratinib Preclinical - Cell culture Actionable In a preclinical study, treatment with Nerlynx (neratinib) resulted in growth inhibition in transformed human breast cell lines expressing ERBB2 (HER2) L755S in culture (PMID: 23220880). 23220880
ERBB2 L755S Her2-receptor negative breast cancer predicted - sensitive HER2 Inhibitor Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in complete response in 1 patient, partial response in 1 patient, stable disease in 2 patients, and progressive disease in 4 patients with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) L755S (PMID: 29420467; NCT01953926). 29420467
ERBB2 L755S colorectal cancer resistant Cetuximab Preclinical Actionable In a preclinical study, colorectal cancer cells over expressing ERBB2 (HER2) L755S were resistant to Erbitux (cetuximab) in culture (PMID: 26243863). 26243863
ERBB2 L755S colon cancer sensitive HER2 Inhibitor Neratinib Phase II Actionable In a Phase II trial, Nerlynx (neratinib) demonstrated activity in metastatic breast cancer patients harboring ERBB2 (HER2) mutations, resulting in a clinical benefit rate of 31% (5/16), with 1 complete response, 1 partial response in a patient with ERBB2 (HER2) L755S, and 3 patients achieving stable disease for 24 weeks or more (PMID: 28679771). 28679771
ERBB2 L755S 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) L755S in culture (PMID: 26243863). 26243863
ERBB2 L755S colon cancer sensitive Trastuzumab Preclinical Actionable In a preclinical study, Herceptin (trastuzumab) inhibited colony formation in transformed mouse colon epithelial cells over expressing ERBB2 (HER2) L755S in culture (PMID: 26243863). 26243863
ERBB2 L755S Advanced Solid Tumor sensitive WZ4002 Preclinical Actionable In a preclinical study, WZ4002 inhibited proliferation of transformed cell lines expressing ERBB2 (HER2) L755S in culture (PMID: 22046346). 22046346
ERBB2 L755S Advanced Solid Tumor resistant HER2 Inhibitor AEE788 Preclinical Actionable In a preclinical study, transformed cell lines expressing ERBB2 (HER2) L755S demonstrated resistance to AEE788 in culture, except at very high doses (PMID: 22046346). 22046346
ERBB2 L755S 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) L755S in culture (PMID: 26243863). 26243863
ERBB2 L755S Her2-receptor positive breast cancer resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, expression of ERBB2 (HER2) L755S conferred resistance to Tykerb (lapatinib) in ERBB2 (HER2)-positive breast cancer cell lines in culture (PMID: 28487443). 28487443
ERBB2 L755S colorectal cancer sensitive HER2 Inhibitor Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited growth of colorectal cancer cells over expressing ERBB2 (HER2) L755S in culture (PMID: 26243863). 26243863
ERBB2 L755S Advanced Solid Tumor resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ERBB2 L755S demonstrated resistance when treated with Tykerb (lapatinib) in culture (PMID: 22046346). 23220880 22046346
ERBB2 L755S biliary tract cancer no benefit HER2 Inhibitor Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease in one and stable disease in another patient with biliary tract cancer harboring ERBB2 (HER2) L755S (PMID: 29420467; NCT01953926). 29420467
ERBB2 L755S colorectal cancer resistant Panitumumab Preclinical Actionable In a preclinical study, colorectal cancer cells over expressing ERBB2 (HER2) L755S were resistant to Vectibix (panitumumab) in culture (PMID: 26243863). 26243863
ERBB2 L755S Advanced Solid Tumor sensitive EKI-285 Preclinical Actionable In a preclinical study, EKI-285 (CL-387785) inhibited proliferation of transformed cell lines expressing ERBB2 (HER2) L755S in culture (PMID: 22046346). 22046346
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 Recruiting
NCT02675829 Phase II trastuzumab emtansine Trial of Ado-Trastuzumab Emtansine for Patients With HER2 Amplified or Mutant Cancers Active, not recruiting