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BIOMARKER:

HER-2 D769H

i
Entrez ID:
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
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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
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Enhertu (fam-trastuzumab deruxtecan-nxki)
11ms
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
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HER-2 (Human epidermal growth factor receptor 2) • TYK2 (Tyrosine Kinase 2)
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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
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
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HER-2 (Human epidermal growth factor receptor 2)
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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
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Enhertu (fam-trastuzumab deruxtecan-nxki)
over1year
Dramatic Response to Pyrotinib and T-DM1 in HER2-Negative Metastatic Breast Cancer With 2 Activating HER2 Mutations. (PubMed, Oncologist)
Herein, we describe a case in which a patient with estrogen receptor-positive/HER2-negative metastatic ILC with 2 activating HER2 mutations (D769H and V777L) exhibited a significant and durable response to anti-HER2 treatment with pyrotinib (an irreversible TKI) in combination with ado-trastuzumab emtansine, which was administered after multiple lines of therapy that had resulted in disease progression. Further, based on the evidence from the present case, TKI plus ADC seems to be a promising combination anti-HER2 regimen for patients with HER2-negative/HER2-mutated advanced BC, although further rigorous studies are warranted to confirm these findings.
Journal • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
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HER-2 positive • ER positive • HER-2 negative • HER-2 V777L • ER positive + HER-2 negative • HER-2 D769H
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Kadcyla (ado-trastuzumab emtansine) • Irene (pyrotinib)
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
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ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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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
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Nerlynx (neratinib)
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
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 mutation • HER-2 S310F • HER-2 D769H • HER-2 R678Q
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Keytruda (pembrolizumab) • Avastin (bevacizumab) • Nerlynx (neratinib)
over2years
HER2 alterations and prognostic implications in all subtypes of breast cancer. (ASCO 2022)
ERBB2mts& fusions were observed in all breast cancer subtypes - more commonly in HER2+, metastatic, & lobular histology tumors - & did not influence prognosis. These alterations may reflect response to treatment pressures in HER2+ disease to reactivate HER2-mediated growth pathways following anti-HER2 therapy & may represent a targetable upregulated oncogenic pathway in HER2- disease. Ongoing identification of ERBB2 alterations may augment treatment options for breast cancer pts & clinical outcomes from this approach are under investigation.
Tumor mutational burden
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HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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TMB-H • HER-2 overexpression • HER-2 negative • HER-2 mutation • HER-2 L755S • HER-2 S310F • ERBB3 mutation • HER-2 D769H • HER-2 fusion
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MI Tumor Seek™
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
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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
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Nerlynx (neratinib)
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
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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
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Nerlynx (neratinib)
4years
[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
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
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HER-2 positive • TMB-H • MSI-H/dMMR • HER-2 amplification • HER-2 L869R • HER-2 D769H
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Keytruda (pembrolizumab) • Herceptin (trastuzumab) • cisplatin • capecitabine
4years
[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
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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
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Keytruda (pembrolizumab) • Herceptin (trastuzumab) • cisplatin • capecitabine
over4years
Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer. (PubMed, J Oncol)
Drugs such as trastuzumab, pertuzumab, lapatinib, neratinib, and the more recent afatinib target the deregulation of HER2 expression. These data suggest that exploring HER2 SNPs in each patient could help individualize anti-HER2 therapies. Advances in our understanding of the genetics of the HER2 gene and its relations with the efficacy of anti-HER2 treatments are needed to improve the outcomes of patients with this aggressive breast cancer.
Review • Journal
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 positive • HER-2 overexpression • HER-2 mutation • HER-2 L755S • HER-2 D769Y • HER-2 V842I • HER-2 D769H
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Herceptin (trastuzumab) • Gilotrif (afatinib) • lapatinib • Nerlynx (neratinib) • Perjeta (pertuzumab)
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
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EGFR (Epidermal growth factor receptor)
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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
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Pozenveo (poziotinib)