^
    1m
    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)
    10ms
    DESTINY-PanTumor01: A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations (clinicaltrials.gov)
    P2, N=102, Active, not recruiting, AstraZeneca | Trial completion date: Jan 2028 --> Jul 2026
    Trial completion date • Metastases
    |
    HER-2 mutation • HER-2 L755S • HER-2 S310F • HER-2 V777L • HER-2 S310Y • HER-2 G778_P780dup • HER-2 D769Y • HER-2 V842I • HER-2 A775 • HER-2 D769H • HER-2 G660D + HER-2 S310F • HER-2 P780-Y781insGSP • HER-2 R678Q • HER-2 T862A • HER-2 YVMA
    |
    Enhertu (fam-trastuzumab deruxtecan-nxki)
    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)
    over1year
    Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with solid tumors harboring specific HER2-activating mutations (HER2m): Primary results from the international phase II DESTINY-PanTumor01 (DPT-01) study (ESMO 2023)
    In heavily pretreated pts with limited Tx options, T-DXd demonstrated encouraging anticancer activity and long DoR across multiple tumor types with HER2m and a range of HER2 expression levels, with a known safety profile. Translational research will help characterize pts who may derive greatest benefit from T-DXd.
    Clinical • P2 data • Pan tumor
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 positive • HER-2 overexpression • HER-2 mutation • HER-2 L755S • HER-2 S310F • HER-2 V777L • HER-2 S310Y • HER-2 G778_P780dup • HER-2 V842I • HER-2 A775 • HER-2 D769H • HER-2 P780-Y781insGSP • HER-2 R678Q • HER-2 T862A • HER-2 YVMA
    |
    Enhertu (fam-trastuzumab deruxtecan-nxki)
    over1year
    NCI-2017-00831: Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC (clinicaltrials.gov)
    P2; Trial completion date: Mar 2024 --> Sep 2024 | Trial primary completion date: Mar 2024 --> Sep 2024
    Trial completion date • Trial primary completion date • EGFR exon 20 • HER2 exon 20 • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 V777L • EGFR exon 20 mutation • HER-2 A775 • HER-2 P780-Y781insGSP • HER-2 YVMA • HER-2 exon 19 mutation • HER-2 exon 23 mutation
    |
    FoundationOne® CDx • Guardant360® CDx • cobas® EGFR Mutation Test v2 • therascreen® EGFR RGQ PCR Kit
    |
    Pozenveo (poziotinib)
    almost2years
    JIN-A04, highly effective tyrosine kinase inhibitor targeting HER2 exon 20 insertion mutations in NSCLC (AACR 2023)
    It was superior to Mobocertinib (IC50 = 27.1 nM for YVMA and IC50 = 3.3 nM for GSP) and comparable with Poziotinib (IC50 = 3.4 nM for YVMA and IC50 = 0.4 nM for GSP). JIN-A04 is highly potent against HER2 exon 20 insertion mutations including YVMA and GSP, while largely sparing HER2 WT activity. Also, JIN-A04 demonstrated effective HER2 pathway inhibition. Based on these robust activities for HER2 exon 20 insertion, JIN-A04 is expected to provide a potent therapeutic opportunity for NSCLC patients with HER2 exon20 insertion mutations.
    HER2 exon 20
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • HER-2 mutation • HER-2 expression • HER-2 exon 20 insertion • HER-2 A775_G776insYVMA • HER-2 exon 20 mutation • HER-2 A775 • HER-2 P780-Y781insGSP • HER-2 YVMA • HER-2 exon 23 mutation
    |
    Pozenveo (poziotinib) • Exkivity (mobocertinib) • YH42946
    almost2years
    NCI-2017-00831: Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC (clinicaltrials.gov)
    P2; Trial completion date: Mar 2023 --> Mar 2024 | Trial primary completion date: Mar 2023 --> Mar 2024
    Trial completion date • Trial primary completion date • EGFR exon 20 • HER2 exon 20 • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 V777L • EGFR exon 20 mutation • HER-2 A775 • HER-2 P780-Y781insGSP • HER-2 YVMA • HER-2 exon 19 mutation • HER-2 exon 23 mutation
    |
    FoundationOne® CDx • Guardant360® CDx • cobas® EGFR Mutation Test v2 • therascreen® EGFR RGQ PCR Kit
    |
    Pozenveo (poziotinib)
    almost2years
    NCI-2017-00831: Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC (clinicaltrials.gov)
    P2; Recruiting --> Active, not recruiting | N=80 --> 116
    Enrollment change • Enrollment closed • EGFR exon 20 • HER2 exon 20 • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 V777L • EGFR exon 20 mutation • HER-2 A775 • HER-2 P780-Y781insGSP • HER-2 YVMA • HER-2 exon 19 mutation • HER-2 exon 23 mutation
    |
    FoundationOne® CDx • Guardant360® CDx • cobas® EGFR Mutation Test v2 • therascreen® EGFR RGQ PCR Kit
    |
    Pozenveo (poziotinib)
    over2years
    Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC (clinicaltrials.gov)
    P2; Trial primary completion date: Mar 2022 --> Mar 2023
    Trial primary completion date • EGFR exon 20
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 V777L • EGFR exon 20 mutation • HER-2 A775 • HER-2 P780-Y781insGSP • HER-2 exon 19 mutation • HER-2 exon 23 mutation
    |
    FoundationOne® CDx • Guardant360® CDx • cobas® EGFR Mutation Test v2 • therascreen® EGFR RGQ PCR Kit
    |
    Pozenveo (poziotinib)
    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
    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)
    over3years
    Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC (clinicaltrials.gov)
    P2; Trial completion date: Mar 2021 --> Mar 2023 | Trial primary completion date: Mar 2021 --> Mar 2022
    Trial completion date • Trial primary completion date • EGFR exon 20
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 V777L • EGFR exon 20 mutation • HER-2 A775 • HER-2 P780-Y781insGSP • HER-2 exon 19 mutation • HER-2 exon 23 mutation
    |
    FoundationOne® CDx • Guardant360® CDx
    |
    Pozenveo (poziotinib)
    over3years
    [VIRTUAL] Efficacy and safety of pan-ErbB inhibitor pyrotinib combined with antiangiogenic agent apatinib for HER2-mutant or amplified metastatic NSCLC: A phase II clinical study. (ASCO 2021)
    Pyrotinib combined with apatinib showed potent anti-tumor activity and acceptable safety profile in metastatic NSCLC with HER2 amplification or activating mutations.
    Clinical • P2 data
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 amplification • HER-2 A775_G776insYVMA • HER-2 exon 20 mutation • HER-2 A775 • HER-2 P780-Y781insGSP
    |
    AiTan (rivoceranib) • Irene (pyrotinib)
    4years
    [VIRTUAL] Real-World Experience of NGS-Based Molecular Profiling in ‘Triple-Negative’ (EGFR/ALK/ROS1) Advanced NSCLC: Should we keep Testing Smokers? (IASLC-WCLC 2020)
    Since clinically significant results were obtained only in non-smoker patients, we suggest smoking status as a potential clinical driver for selecting aNSCLC patients for NGS analyses in a real-world context. NGS testing of smokers might be considered within the research setting.
    Clinical • Real-World Evidence • Next-generation sequencing
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4) • FGFR (Fibroblast Growth Factor Receptor) • KIF5B (Kinesin Family Member 5B)
    |
    BRAF V600E • EGFR mutation • KRAS G12C • BRAF V600 • RET fusion • MET exon 14 mutation • EML4-ALK fusion • ALK fusion • KIF5B-RET fusion • MET mutation • KRAS G12 • EGFR exon 18 mutation • EGFR negative • HER-2 P780-Y781insGSP