^
    2ms
    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
    ERBB2 mutations in metastatic colorectal cancer: From clinicopatholgical features to potential treatment implications in a real-world cohort (ESMO-GI 2023)
    Among patients with any ERBB2 mutations, 7 received a combination of chemotherapy plus anti-EGFR, either cetuximab or panitumumab, 6 had PR and 1 SD as best response. In this consecutive real-world series, ERBB2 activating mutation prevalence was 3.1%. We found an addition 4.4% ERBB2 VUS prevalence, with a ERBB2 mutation prevalence of 7.5% as a whole. Pathogenetic mutations can co-occur with other driver molecular alterations.
    Clinical • Real-world evidence • Real-world • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene)
    |
    BRAF mutation • HER-2 amplification • HER-2 mutation • BRAF wild-type • RAS mutation • RAS wild-type • HER-2 V777L • HER-2 R678Q • HER-2 T862A
    |
    Erbitux (cetuximab) • Vectibix (panitumumab)
    almost2years
    Landscape and analysis of ERBB2 amplification and short variant mutations in large-scale Chinese patients with colorectal cancer (AACR 2023)
    The overall variation rate of ERBB2 is 5.4% in Chinese patients with CRC, which is accompanied by significantly different molecular pathological characteristics compared to patients with wild-type ERBB2, and different mutation types (CNV or SNV) display different molecular pathological characteristics.
    Clinical • MSi-H Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MSI (Microsatellite instability)
    |
    TP53 mutation • KRAS mutation • MSI-H/dMMR • BRAF mutation • HER-2 amplification • HER-2 mutation • KRAS wild-type • HER-2 S310F • HER-2 V842I • HER-2 R678Q
    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)
    almost2years
    Targetable HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical and Molecular Correlations (USCAP 2023)
    HER2 mutations are most common in EC among gynecologic cancers, with R678Q most frequent in our cohort, and T862A in cBioportal. While no HER2 -mutated tumors had a 3+ IHC score, increased HER2 expression (2+) was seen in tumors with L313V, R678Q, and T862A mutations, and HER2 rearrangement. Targeted therapy has already been applied in other tumor types with these HER2 mutations; however, further studies are necessary to explore the prognostic and therapeutic implications of these findings in gynecologic cancers.
    Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 amplification • HER-2 negative • HER-2 mutation • HER-2 L755S • HER-2 V777L • HER-2 D769Y • HER-2 R678Q • HER-2 T862A
    2years
    MasterKey-01: A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors. (clinicaltrials.gov)
    P1/2, N=91, Terminated, Black Diamond Therapeutics, Inc. | Completed --> Terminated; The development of BDTX-189 was discontinued by the sponsor.
    Trial termination • HER2 exon 20 • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    EGFR mutation • HER-2 overexpression • HER-2 amplification • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • HER-2 exon 20 insertion • HER-2 L755S • HER-2 V777L • EGFR exon 20 mutation • ERBB3 mutation • HER-2 V842I • HER-2 R678Q • HER-2 exon 23 mutation
    |
    tuxobertinib (BDTX-189)
    over2years
    MasterKey-01: A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors. (clinicaltrials.gov)
    P1/2, N=91, Completed, Black Diamond Therapeutics, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Sep 2022 | Trial primary completion date: Jun 2023 --> Sep 2022
    Trial completion • Trial completion date • Trial primary completion date • HER2 exon 20
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    EGFR mutation • HER-2 overexpression • HER-2 amplification • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • HER-2 exon 20 insertion • HER-2 L755S • HER-2 V777L • EGFR exon 20 mutation • ERBB3 mutation • HER-2 V842I • HER-2 R678Q • HER-2 exon 23 mutation
    |
    tuxobertinib (BDTX-189)
    over2years
    Neratinib in HER2-mutant, recurrent/metastatic cervical cancer (R/M CC): Updated findings from the phase 2 SUMMIT basket trial (ESMO 2022)
    Prior treatments included platinum-based chemotherapy (100%), bevacizumab (73%), and pembrolizumab (18%). No patients discontinued treatment due to diarrhea. Table: 559P CBR, CR + PR + SD ≥16 weeks; CR, complete response; DoR, duration of response; NE, not estimable; ORR, objective response rate; PFS, progression-free survival; PR, partial response; SD, stable disease Conclusions These encouraging results support the clinical benefit of neratinib in this patient population and warrant further investigation following platinum failure.
    P2 data • PD(L)-1 Biomarker • Pan tumor
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 mutation • HER-2 S310F • HER-2 D769H • HER-2 R678Q
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • 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
    MasterKey-01: A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors. (clinicaltrials.gov)
    P1/2, N=91, Active, not recruiting, Black Diamond Therapeutics, Inc. | Recruiting --> Active, not recruiting | N=200 --> 91
    Enrollment closed • Enrollment change
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    EGFR mutation • HER-2 overexpression • HER-2 amplification • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • HER-2 exon 20 insertion • HER-2 L755S • HER-2 V777L • EGFR exon 20 mutation • ERBB3 mutation • HER-2 V842I • HER-2 R678Q • HER-2 exon 23 mutation
    |
    tuxobertinib (BDTX-189)
    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
    ERBB2 Mutations as Potential Predictors for Recurrence in Colorectal Serrated Polyps by Targeted Next-Generation Sequencing. (PubMed, Front Oncol)
    Our results are emphasizing that SP individuals with ERBB2 mutants are at higher risks of subsequent colorectal neoplasms. ERBB2 mutants might work as facilitated markers for prediction of high-risk SPs and might implicate a potential mechanism in the serrated pathway to colorectal carcinoma (CRC).
    Journal • Next-generation sequencing • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSH2 (MutS Homolog 2) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • APC (APC Regulator Of WNT Signaling Pathway)
    |
    BRAF mutation • HER-2 mutation • APC mutation • HER-2 V842I • HER-2 R678Q
    almost3years
    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)
    over3years
    Relationship of HER2 alteration and MSI status in colorectal adenocarcinoma. (PubMed, Oncologist)
    Our study highlights the high MSI-H rate in HER2 mutated cases but no MSI-H in HER2 amplification cases. Moreover MSI-H patients with HER2 mutated had worse PFS for PD-1 antibody than those without. Further research to explore the intern relationship between HER2 alteration and MSI-H is needed.
    Journal • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • MSI (Microsatellite instability)
    |
    MSI-H/dMMR • HER-2 amplification • HER-2 R678Q
    almost4years
    [VIRTUAL] Evaluation of somatic and germline mutations in ampullary carcinoma reveals actionable targets in multiple signaling pathways (AACR 2021)
    The BRAF N581I mutation is resistant to BRAF inhibitor vemurafenib but sensitive to MEK inhibitor trametinib. The PIK3CA N1044K mutation is oncogenic but its sensitivity to PIK3CA inhibitor alpelisib is unknown... Through comprehensive genomic characterization of Chinese AC patients, we identified multiple actionable mutations in multiple signaling pathways. Our findings indicated that molecular profiling can provide clinical benefits to a significant portion of AC patients.
    Tumor Mutational Burden • MSi-H Biomarker • PARP Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • PALB2 (Partner and localizer of BRCA2) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CHEK2 (Checkpoint kinase 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • ELF3 (E74 Like ETS Transcription Factor 3) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4)
    |
    TP53 mutation • KRAS mutation • MSI-H/dMMR • BRAF mutation • HER-2 amplification • PIK3CA mutation • HER-2 mutation • FGFR2 mutation • PALB2 mutation • FGFR2 amplification • CHEK2 mutation • U2AF1 mutation • ERBB3 mutation • ERBB3 G284R • HER-2 R678Q
    |
    Mekinist (trametinib) • Zelboraf (vemurafenib) • Piqray (alpelisib)
    4years
    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)
    4years
    [VIRTUAL] Targeting HER2 (ERBB2) mutation-positive advanced biliary tract cancers with neratinib: Results from the phase II SUMMIT ‘basket’ trial. (ASCO-GI 2021)
    68% of patients received =2 systemic regimens (96% received prior gemcitabine-based regimens). Neratinib is safe and tolerable in patients with advanced BTC patients and somatic HER2 mutations. The antitumor activity of neratinib appears comparable to current standards of care, with similar PFS and OS in heavily pretreated patients. Analysis of co-occurring oncogenic mutations and response is ongoing, and consideration is being given to neratinib-based combination regimens to further improve outcomes in this setting.
    P2 data • Pan tumor
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 mutation • HER-2 L755S • HER-2 S310F • HER-2 V777L • HER-2 V842I • HER-2 R678Q
    |
    MSK-IMPACT
    |
    gemcitabine • Nerlynx (neratinib)
    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)