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    BIOMARKER:

    HER-2 L869R

    i
    Other names: ERBB2, CD340, HER-2, HER2, NEU, NGL, V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2
    Entrez ID:
    2064
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    8d
    NCI-2022-04099: Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene (clinicaltrials.gov)
    P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • CD4 (CD4 Molecule) • CASP3 (Caspase 3)
    |
    HER-2 positive • HER-2 overexpression • HER-2 amplification • HER-2 mutation • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 S310F • HER-2 V777L • HER-2 G778_P780dup • HER-2 D769Y • HER-2 L869R • HER-2 V842I • HER-2 H878Y • HER-2 L866M • HER-2 A775 • HER-2 G309A • HER-2 P780-Y781insGSP • HER-2 R678Q • HER-2 R896C • HER-2 T862A • HER-2 YVMA
    |
    Nerlynx (neratinib) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    4ms
    Characterizing the genomic landscape of breast cancer in an Irish cohort of patients (ESMO 2024)
    We present the largest study of BC variant frequencies in a cohort of Irish breast cancer patients to date and confirm NGS is feasible and identifies clinically relevant and actionable variants. We confirm that the frequency of PIK3CA alterations, in addition to codon specificity, are comparable to those observed in European and US cohorts and demonstrate that the detection of clinically relevant biomarkers is not confined to ER positive HER2 negative BC. The tissue failure rate (19%) underscores the need for cfDNA testing to identify the expanding range of actionable targets in BC to improve access to emerging targeted therapies and biomarker-driven clinical trials.
    Clinical • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    HER-2 positive • ER positive • HER-2 amplification • HER-2 negative • PIK3CA mutation • HER-2 S310F • ESR1 mutation • AKT1 mutation • HER-2 D769Y • HER-2 L869R • ER positive + HER-2 negative • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
    |
    Oncomine Focus Assay
    10ms
    Plasma-based analysis of ERBB2 mutational status by multiplex digital PCR in a large series of patients with metastatic breast cancer. (PubMed, Mol Oncol)
    Matched tumor samples from six patients identified the same mutations with an 83% concordance rate. In summary, our highly sensitive multiplex digital PCR assays are well suited for plasma-based monitoring of ERBB2 mutational status in patients with MBC.
    Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • TYK2 (Tyrosine Kinase 2)
    |
    HR positive • HER-2 negative • HER-2 mutation • HER-2 L755S • HER-2 S310F • HER-2 V777L • EGFR positive • HER-2 S310Y • HER-2 L869R • HER-2 D769H
    1year
    NCI-2022-04099: Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene (clinicaltrials.gov)
    P1, N=30, Recruiting, National Cancer Institute (NCI) | N=18 --> 30
    Enrollment change • Combination therapy
    |
    CD4 (CD4 Molecule)
    |
    HER-2 positive • HER-2 overexpression • HER-2 amplification • HER-2 mutation • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 S310F • HER-2 V777L • HER-2 G778_P780dup • HER-2 D769Y • HER-2 L869R • HER-2 V842I • HER-2 H878Y • HER-2 L866M • HER-2 A775 • HER-2 G309A • HER-2 P780-Y781insGSP • HER-2 R678Q • HER-2 R896C • HER-2 T862A • HER-2 YVMA
    |
    Nerlynx (neratinib) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    almost2years
    Neratinib in Treating Older Patients With Stage IV HER2-Positive Breast Cancer (clinicaltrials.gov)
    P2, N=25, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Sep 2022
    Trial completion • Trial completion date • Metastases
    |
    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    HER-2 positive • HER-2 negative • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 S310F • HER-2 V777L • HER-2 L755P • ERBB3 mutation • HER-2 S310Y • HER-2 G778_P780dup • HER-2 D769Y • HER-2 L869R • HER-2 V842I • ERBB3 V659E • HER-2 G778_S779insCPG • HER-2 L755_T759del • HER-2 A775 • HER-2 D769H • HER-2 R678Q • HER-2 R896C • HER-2 YVMA • ERBB3 L755S
    |
    Nerlynx (neratinib)
    over2years
    NCI-2022-04099: Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene (clinicaltrials.gov)
    P1, N=18, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy
    |
    CD4 (CD4 Molecule)
    |
    HER-2 positive • HER-2 overexpression • HER-2 amplification • HER-2 mutation • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 S310F • HER-2 V777L • HER-2 L755P • HER-2 G778_P780dup • HER-2 D769Y • HER-2 L869R • HER-2 V842I • HER-2 H878Y • HER-2 L866M • HER-2 A775 • HER-2 G309A • HER-2 P780-Y781insGSP • HER-2 R678Q • HER-2 R896C • HER-2 T862A
    |
    Nerlynx (neratinib) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    over2years
    A Study of Poziotinib in Patients With Epidermal Growth Factor Receptor (EGFR) or Human Epidermal Growth Factor Receptor 2 (HER2) Activating Mutations in Advanced Malignancies (clinicaltrials.gov)
    P2, N=1, Terminated, Spectrum Pharmaceuticals, Inc | N=150 --> 1 | Trial completion date: Dec 2023 --> Mar 2022 | Recruiting --> Terminated | Trial primary completion date: Jun 2023 --> Mar 2022; Strategic business decision (unrelated to safety)
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • MSI (Microsatellite instability)
    |
    HER-2 positive • EGFR mutation • MSI-H/dMMR • HER-2 negative • EGFR L858R • HER-2 exon 20 insertion • EGFR L861Q • EGFR G719X • ER negative • EGFR S768I • HER-2 S310F • EGFR positive • HER-2 I655V • HER-2 L869R • HER-2 V842I • EGFR P596L • EGFR R222C • EGFR A750P • EGFR E746 • EGFR L833V • HER-2 R678Q • PGR negative • EGFR V774M
    |
    Pozenveo (poziotinib) • loperamide
    over2years
    NCI-2022-04099: Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene (clinicaltrials.gov)
    P1, N=18, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2023 --> Jun 2024 | Trial primary completion date: Aug 2023 --> Jun 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    CD4 (CD4 Molecule)
    |
    HER-2 positive • HER-2 overexpression • HER-2 amplification • HER-2 mutation • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 S310F • HER-2 V777L • HER-2 L755P • HER-2 G778_P780dup • HER-2 D769Y • HER-2 L869R • HER-2 V842I • HER-2 H878Y • HER-2 L866M • HER-2 A775 • HER-2 G309A • HER-2 P780-Y781insGSP • HER-2 R678Q • HER-2 R896C • HER-2 T862A
    |
    Nerlynx (neratinib) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    over2years
    NCI-2022-04099: Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene (clinicaltrials.gov)
    P1, N=18, Not yet recruiting, National Cancer Institute (NCI)
    New P1 trial • Combination therapy
    |
    CD4 (CD4 Molecule)
    |
    HER-2 positive • HER-2 overexpression • HER-2 amplification • HER-2 mutation • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 S310F • HER-2 V777L • HER-2 L755P • HER-2 G778_P780dup • HER-2 D769Y • HER-2 L869R • HER-2 V842I • HER-2 H878Y • HER-2 L866M • HER-2 A775 • HER-2 G309A • HER-2 P780-Y781insGSP • HER-2 R678Q • HER-2 R896C • HER-2 T862A
    |
    Nerlynx (neratinib) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    over2years
    Neratinib in Treating Older Patients With Stage IV HER2-Positive Breast Cancer (clinicaltrials.gov)
    P2, N=25, Active, not recruiting, City of Hope Medical Center | N=40 --> 25 | Trial completion date: Oct 2021 --> Dec 2022
    Enrollment change • Trial completion date
    |
    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    HER-2 positive • HER-2 negative • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 S310F • HER-2 V777L • HER-2 L755P • ERBB3 mutation • HER-2 S310Y • HER-2 G778_P780dup • HER-2 D769Y • HER-2 L869R • HER-2 V842I • ERBB3 V659E • HER-2 G778_S779insCPG • HER-2 L755_T759del • HER-2 A775 • HER-2 D769H • HER-2 R678Q • HER-2 R896C • ERBB3 L755S
    |
    Nerlynx (neratinib)
    almost4years
    Neratinib in Treating Older Patients With Stage IV HER2-Positive Breast Cancer (clinicaltrials.gov)
    P2, N=40, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2020 --> Oct 2021 | Trial primary completion date: Oct 2020 --> Oct 2021
    Clinical • Trial completion date • Trial primary completion date
    |
    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • IL6 (Interleukin 6)
    |
    HER-2 positive • HER-2 negative • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 S310F • HER-2 V777L • HER-2 L755P • ERBB3 mutation • HER-2 S310Y • HER-2 G778_P780dup • HER-2 D769Y • HER-2 L869R • HER-2 V842I • ERBB3 V659E • HER-2 G778_S779insCPG • HER-2 L755_T759del • HER-2 A775 • HER-2 D769H • HER-2 R678Q • HER-2 R896C • ERBB3 L755S
    |
    Nerlynx (neratinib)
    almost4years
    [VIRTUAL] A multi-institutional phase Ib/II trial of first-line triplet regimen (Pembrolizumab, Trastuzumab, Chemotherapy) for HER2-positive advanced gastric and gastroesophageal junction cancer (PANTHERA Trial): Molecular profiling and clinical update. (ASCO-GI 2021)
    Pembrolizumab 200mg IV D1, Trastuzumab 6mg/kg (after 8mg/kg load) D1, Capecitabine 1000mg/m2 bid D1-14, and Cisplatin 80mg/m2 D1 every 3 weeks was selected as recommended phase II dose. First-line triplet regimen (Pembrolizumab, Trastuzumab, and Chemotherapy) showed promising efficacy based on HER2 amplification by NGS regardless of PD-L1 status in AGC/GEJ cancer. Correlative biomarkers found from NGS study need to be validated through on-going phase III Keynote-811 study (NCT03615326). Response and Survival of PANTHERA Trial (cut-off date: Aug-31-2020).
    Clinical • P1/2 data • Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
    |
    HER-2 positive • TMB-H • MSI-H/dMMR • HER-2 amplification • HER-2 L869R • HER-2 D769H
    |
    Keytruda (pembrolizumab) • Herceptin (trastuzumab) • cisplatin • capecitabine
    almost4years
    [VIRTUAL] A multi-institutional phase Ib/II trial of first-line triplet regimen (Pembrolizumab, Trastuzumab, Chemotherapy) for HER2-positive advanced gastric and gastroesophageal junction cancer (PANTHERA Trial): Molecular profiling and clinical update. (ASCO-GI 2021)
    Pembrolizumab 200mg IV D1, Trastuzumab 6mg/kg (after 8mg/kg load) D1, Capecitabine 1000mg/m2 bid D1-14, and Cisplatin 80mg/m2 D1 every 3 weeks was selected as recommended phase II dose. First-line triplet regimen (Pembrolizumab, Trastuzumab, and Chemotherapy) showed promising efficacy based on HER2 amplification by NGS regardless of PD-L1 status in AGC/GEJ cancer. Correlative biomarkers found from NGS study need to be validated through on-going phase III Keynote-811 study (NCT03615326). Response and Survival of PANTHERA Trial (cut-off date: Aug-31-2020).
    Clinical • P1/2 data • Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
    |
    HER-2 positive • TMB-H • MSI-H/dMMR • HER-2 amplification • HER-2 L869R • HER-2 D769H
    |
    Keytruda (pembrolizumab) • Herceptin (trastuzumab) • cisplatin • capecitabine
    over4years
    [VIRTUAL] Genomic architecture of gallbladder cancer: Results of a first prospective study. (ASCO 2020)
    Phase 2 trial of frontline Trastuzumab combined with chemotherapy is ongoing... GBC is enriched in 28% of patients with ERBB2 & ERBB3 amplifications and/or mutations. FGFR2 mutation is rare in GBC. PIK3CA aberrations are common.
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    PD-L1 expression • KRAS mutation • HER-2 amplification • PIK3CA mutation • MET amplification • FGFR2 mutation • NF1 mutation • FGFR2 amplification • FGFR3 mutation • KRAS G12A • PIK3CA amplification • HER-2 S310F • HER-2 V777L • KRAS G12 • KRAS G13 • NF2 mutation • ERBB3 mutation • HER-2 L869R • ERBB3 G284R • FGFR3 amplification
    |
    Herceptin (trastuzumab)
    almost5years
    A Study of Poziotinib in Patients With EGFR or HER2 Activating Mutations in Advanced Malignancies (clinicaltrials.gov)
    P2, N=150, Recruiting, Spectrum Pharmaceuticals, Inc | Not yet recruiting --> Recruiting
    Clinical • Enrollment open
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • HER-2 amplification • EGFR L858R • HER-2 mutation • EGFR T790M • HER-2 exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • HER-2 S310F • HER-2 V777L • EGFR E709K • HER-2 I655V • HER-2 L869R • HER-2 V842I • EGFR P596L • EGFR R222C • HER-2 T798M • EGFR E746 • HER-2 D769H • HER-2 R678Q • HER-2 T798I • HER-2 mutation + HER-2 T798I • EGFR V774M
    |
    Pozenveo (poziotinib)