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BIOMARKER:

HER-2 exon 20 mutation

i
Other names: ERBB2, CD340, HER-2, HER2, NEU, NGL, V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2
Entrez ID:
2ms
Efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy as 1st line treatment for patients with non-small cell lung cancer harboring HER2 mutations: Results from LC-SCRUM-Asia. (PubMed, Lung Cancer)
Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with HER2-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with HER2-mutant NSCLC receiving platinum-based chemotherapy with ICIs.
Journal • Checkpoint inhibition • Tumor mutational burden • IO biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden)
|
EGFR mutation • TMB-H • HER-2 mutation • HER-2 exon 20 insertion • ALK fusion • HER-2 exon 20 mutation
2ms
Prevalence and treatment of human epidermal growth factor receptor 2-altered non-small cell lung cancer: a retrospective analysis and systematic literature review. (PubMed, Ecancermedicalscience)
Finally, phase II clinical trials involving HER2-altered NSCLC patients demonstrated promising treatment outcomes with trastuzumab deruxtecan, trastuzumab emtansine, pyrotinib, pyrotinib + apatinib and trastuzumab + pertuzumab + docetaxel. In conclusion, the prevalence of HER2 alteration among Malaysian NSCLC patients falls within the global range. A systematic review of clinical trials revealed promising treatment outcomes and Malaysian NSCLC patients with HER2 alterations are anticipated to similarly benefit from HER2-targeted therapies.
Retrospective data • Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 amplification • HER-2 exon 20 insertion • HER-2 exon 20 mutation • HER-2 A775 • HER-2 exon 23 mutation
|
docetaxel • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • AiTan (rivoceranib) • Irene (pyrotinib)
2ms
Molecular landscape of ERBB2 alterations in 3000 advanced NSCLC patients. (PubMed, NPJ Precis Oncol)
Notably, EGFR ex20 insertions exhibited greater insertion diversity. Clinical characteristics of EGFR and ERBB2 ex20 NSCLC were similar, characterized by low tumor mutation burden (TMB), a predominant never-smoker population, and a majority of lung adenocarcinoma cases.
Journal • Tumor mutational burden • Metastases
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden)
|
HER-2 mutation • TMB-L • HER-2 exon 20 mutation • HER-2 A775 • HER-2 YVMA
|
Guardant360® CDx
8ms
Clinicopathologic and Molecular Characteristics of HER2 (ERBB2)-Altered Non-Small Cell Lung Cancer: Implications for Precision Medicine. (PubMed, Mod Pathol)
In addition, the above clinicopathological characteristics and HER2 IHC results can be valuable determinants for identifying patients with HER2-altered NSCLC. These insights hold promise for the development of more effective diagnostic and therapeutic strategies for this complex subset of NSCLC patients.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
|
EGFR mutation • HER-2 amplification • HER-2 mutation • HER-2 exon 20 insertion • HER-2 exon 20 mutation • HER-2 exon 23 mutation
9ms
New P2 trial • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 mutation • HER-2 exon 20 insertion • HER-2 L755S • HER-2 exon 20 mutation • HER-2 YVMA • HER-2 exon 23 mutation
|
Herceptin (trastuzumab) • docetaxel • Perjeta (pertuzumab)
9ms
The safety and efficacy of anti-PD-1 inhibitor-based combinational therapy in non-small cell lung cancer patients with oncogenic alterations. (PubMed, Transl Cancer Res)
The anti-PD-1 inhibitor-based combinational therapy elicited exciting anti-tumor efficacy and prolonged patient survival with manageable adverse effects in NSCLC patients harboring oncogenic alterations. The PD-L1 status and LIPI could be used as a biomarker predicting response to anti-PD-1 inhibitor-based combinational treatment in these patients.
Journal • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene)
|
BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • EGFR L858R • ALK rearrangement • HER-2 exon 20 insertion • RAS mutation • RET mutation • RET rearrangement • HER-2 exon 20 mutation • EGFR L858R + EGFR exon 21 deletion • HER-2 exon 23 mutation
11ms
Trial completion date • Trial initiation date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 mutation • HER-2 exon 20 insertion • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
Irene (pyrotinib) • Aidixi (disitamab vedotin)
12ms
R2D2: Her2-positive Lung Cancer Treated With Dedicated Drug (clinicaltrials.gov)
P2, N=46, Completed, Intergroupe Francophone de Cancerologie Thoracique | Active, not recruiting --> Completed
Trial completion
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 mutation • HER-2 exon 20 insertion • HER-2 L755S • HER-2 exon 20 mutation • HER-2 YVMA • HER-2 exon 23 mutation
|
Herceptin (trastuzumab) • docetaxel • Perjeta (pertuzumab)
12ms
A Study of RC48-ADC in Subjects With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov)
P1/2, N=37, Completed, RemeGen Co., Ltd. | Active, not recruiting --> Completed
Trial completion • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • HER-2 overexpression • HER-2 mutation • MET amplification • EGFR T790M • MET mutation • HER-2 exon 20 mutation
|
Aidixi (disitamab vedotin)
1year
Pyrotinib plus antiangiogenic agents for HER2-altered advanced non-small cell lung cancer: A retrospective real-world study. (PubMed, Thorac Cancer)
In this study, pyrotinib plus antiangiogenic agents demonstrated promising efficacy and were tolerable in HER2-altered NSCLC patients.
Retrospective data • Journal • Real-world evidence • Real-world • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 exon 20 insertion • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
Avastin (bevacizumab) • Focus V (anlotinib) • AiTan (rivoceranib) • Irene (pyrotinib)
1year
Improved Survival Outcomes in Patients With MET-Dysregulated Advanced NSCLC Treated With MET Inhibitors: Results of a Multinational Retrospective Chart Review. (PubMed, Clin Lung Cancer)
MET alterations in NSCLC typically occur in the absence of other oncogenic driver mutations and are associated with poor survival outcomes. Notably, METi therapies are associated with improved survival outcomes in patients with MET-dysregulated NSCLC.
Retrospective data • Review • Journal • Metastases
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
MET amplification • ALK rearrangement • EGFR wild-type • MET exon 14 mutation • HER-2 exon 20 insertion • RET rearrangement • HER-2 exon 20 mutation • HER-2 exon 23 mutation
1year
New P1 trial • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene)
|
EGFR mutation • HER-2 overexpression • BRAF mutation • HER-2 amplification • EGFR L858R • HER-2 mutation • EGFR exon 19 deletion • MET amplification • EGFR T790M • RET fusion • HER-2 exon 20 insertion • ALK fusion • EGFR L861Q • RAS mutation • EGFR G719X • EGFR S768I • HER-2 exon 20 mutation • BRAF amplification • HER-2 exon 23 mutation
|
Erbitux (cetuximab) • Tagrisso (osimertinib) • Tukysa (tucatinib)
1year
R2D2: Her2-positive Lung Cancer Treated With Dedicated Drug (clinicaltrials.gov)
P2, N=46, Active, not recruiting, Intergroupe Francophone de Cancerologie Thoracique | Trial completion date: Jul 2023 --> Feb 2024
Trial completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 mutation • HER-2 exon 20 insertion • HER-2 L755S • HER-2 exon 20 mutation • HER-2 YVMA • HER-2 exon 23 mutation
|
Herceptin (trastuzumab) • docetaxel • Perjeta (pertuzumab)
over1year
Trastuzumab deruxtecan (DS8201) for advanced non-small cell lung cancer with HER2 exon 20 insertion mutation: a case report. (PubMed, Anticancer Drugs)
After treatment with T-DXd, the tumor significantly regressed and bone metastasis improved, maintaining a state of no progression for 21 months. This case report evidences the use of T-DXd in the treatment of NSCLC with HER2 exon 20 insertion mutation.
Journal • HER2 exon 20 • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive • HER-2 amplification • HER-2 mutation • HER-2 expression • HER-2 exon 20 insertion • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
Enhertu (fam-trastuzumab deruxtecan-nxki)
over1year
Micropapillary histology (MPUC) and extra-cellular domain ERBB2 (ERBB2 ECD+) mutations in urothelial bladder cancer (UBC) (ESMO 2023)
Background Given the early promising data with afatinib in advanced UC and the recent approval in NSCLC for anti-HER2 targeted therapy for activating kinase domain exon 20 ERBB2 insertion mutations, there is considerable interest in targeting additional locations in the ERBB2 gene in other tumor types...Conclusions ERBB2 ECD mutation-driven UBC represents a distinct subtype of UBC featuring an enrichment of MPUC histology from 1-2% to 28% incidence in ERBB2 ECD mutated UBC, and unique clinical and molecular characteristics, including differences in mutational signatures and genetic ancestry. Further exploration of anti-HER2 targeted therapy for non-amp sequence mutations in ERBB2 in UBC appears warranted.
Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • RB1 (RB Transcriptional Corepressor 1) • MTAP (Methylthioadenosine Phosphorylase) • KMT2D (Lysine Methyltransferase 2D)
|
PD-L1 expression • MSI-H/dMMR • PD-L1 overexpression • HER-2 amplification • HER-2 mutation • HER-2 S310F • HER-2 S310Y • HER-2 exon 20 mutation • HER-2 amplification + PD-L1 expression • PD-L1 expression + MSI-H/dMMR
|
PD-L1 IHC 22C3 pharmDx
|
Gilotrif (afatinib)
over1year
Clinicopathologic characteristics and outcomes to immune checkpoint inhibitor therapy in patients with HER2-altered metastatic non-small cell lung cancer (ESMO 2023)
Conclusions In comparison to patients with classical EGFR alterations, those with HER2 alterations and advanced NSCLC have similar poor outcomes to treatment with ICI therapy. A comprehensive analysis of the tumor immune microenvironment may provide insight into future biomarkers of response.
Clinical • Checkpoint inhibition • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • HER-2 exon 20 insertion • HER-2 exon 20 mutation • HER-2 exon 23 mutation
over1year
Preclinical activity of ORIC-114, a highly selective, brain penetrant, irreversible kinase inhibitor, against atypical mutations in EGFR (ESMO 2023)
Conclusions ORIC-114 demonstrated best-in-class properties including high free unbound exposure in brain, exquisite selectivity across the kinome, and potent activity across atypical mutations in EGFR, including PACC mutations and exon 20 insertion mutations. ORIC-114 is a promising therapy for NSCLC patients with atypical mutations in EGFR, including those with active CNS metastases, and is currently being evaluated in a global clinical trial (NCT05315700).
Preclinical
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
EGFR mutation • EGFR exon 20 insertion • HER-2 exon 20 mutation
|
ORIC-114
over1year
Efficacy of poziotinib in HER2 exon 20 insertion NSCLC patients who received prior platinum-based and HER2 targeted therapies (ESMO 2023)
Of these, 35 patients (25 16 mg QD; 10 8 mg BID) had prior HER2 therapy such as trastuzumab, TDM1, and T-DXd...ORRs were 30% with PLT+any systemic therapy; 30% with PLT+docetaxel and 43% with PLT+TKI...Conclusions Poziotinib demonstrated clinically meaningful efficacy in patients who received prior 2+ lines of therapy including HER2 therapy. ZENITH20 study provides a large dataset in the 3rd or later line setting of HER2 exon 20 mutations in NSCLC who have very limited treatment options.
Clinical • HER2 exon 20
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • HER-2 mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • EGFR exon 20 mutation • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
docetaxel • Enhertu (fam-trastuzumab deruxtecan-nxki) • Pozenveo (poziotinib)
over1year
Early evidence of efficacy in patients (pts) with non-small cell lung cancer (NSCLC) with HER2 exon20 insertion (ex20ins) mutations treated in a phase I study with BAY 2927088 (ESMO 2023)
In pts with HER2 ex20ins mutant disease, BAY 2927088 showed encouraging preliminary anti-tumour activity. These results warrant further investigation of BAY 2927088 in pts with NSCLC.
Clinical • P1 data
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
EGFR mutation • HER-2 mutation • HER-2 exon 20 insertion • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
BAY 2927088
over1year
Journal • HER2 exon 20
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 mutation • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
Pozenveo (poziotinib)
over1year
Efficacy and Safety of Poziotinib in HER2 Exon 20 Insertion NSCLC Patients who Received at Least 2 Previous Systemic Therapies (IASLC-WCLC 2023)
Introduction: HER2 mutation is a newly established actionable target in non-small cell lung cancer (NSCLC) with trastuzumab-deruxtecan (T-DXd) as the only approved targeted therapy for patients as 2nd line therapy...ORRs were 31.3% with platinum+any systemic therapy; 30.8% with platinum+docetaxel; 24.0% with platinum+HER2 antibody-based therapy; 54.5% with platinum+TKI... Poziotinib demonstrated clinically meaningful efficacy in patients who received and progressed on prior 2+ lines of therapy regardless of types and sequence of treatment. ZENITH20 study provides a large dataset in the 3rd or later line setting of HER2 exon 20 mutations NSCLC patients who have very limited treatment options. No new safety signal was detected in this patient population.
Clinical • IO biomarker • HER2 exon 20
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
EGFR mutation • HER-2 mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • EGFR exon 20 mutation • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
docetaxel • Enhertu (fam-trastuzumab deruxtecan-nxki) • Pozenveo (poziotinib)
over1year
Beamion Lung 1, a Phase Ia/Ib Trial of the HER2 TKI, BI 1810631 in Patients with Advanced Solid Tumors with HER2 Aberrations (IASLC-WCLC 2023)
These preliminary data indicate that BI 1810631 is well tolerated and shows strong efficacy signals across all dose levels in patients with pre-treated HER2 aberration-positive solid tumors. Recruitment into Phase Ib is ongoing with the QD regimen. Updated Phase Ia data, and emerging Phase Ib data, will be presented.
Clinical • P1 data • Metastases
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 overexpression • HER-2 amplification • HER-2 mutation • HER-2 exon 20 mutation
|
zongertinib (BI 1810631)
over1year
Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)
P2, N=240, Recruiting, German Cancer Research Center | Not yet recruiting --> Recruiting
Enrollment open
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
|
HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PALB2 mutation • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation
|
Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Itovebi (inavolisib) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
over1year
Pertuzumab Plus Trastuzumab in Patients With Lung Cancer With ERBB2 Mutation or Amplification: Results From the Targeted Agent and Profiling Utilization Registry Study. (PubMed, JCO Precis Oncol)
Combination P + T showed evidence of antitumor activity in heavily pretreated patients with non-small-cell lung cancer and ERBB2 mutation or amplification, particularly those with ERBB2 exon 20 insertion mutations.
Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 amplification • HER-2 mutation • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
Herceptin (trastuzumab) • Perjeta (pertuzumab)
over1year
Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)
P2, N=240, Not yet recruiting, German Cancer Research Center | Trial completion date: Dec 2029 --> Dec 2030 | Trial primary completion date: Apr 2029 --> Mar 2030
Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
|
HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PALB2 mutation • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation
|
Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Itovebi (inavolisib) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
over1year
Immunotherapy for non-small cell lung cancer with EGFR or HER2 exon 20 insertion mutations: a real-world analysis. (PubMed, Transl Lung Cancer Res)
One patient discontinued treatment due to a grade 3 rash after three cycles of ICI plus anlotinib treatment. The results showed that immunotherapy combined with chemotherapy may play a role in the first-line treatment of NSCLC patients with ex20ins mutations. This finding requires further investigation for application.
Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • EGFR exon 20 • HER2 exon 20 • Real-world
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
EGFR mutation • HER-2 mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • EGFR exon 20 mutation • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
Focus V (anlotinib)
over1year
Pyrotinib plus antiangiogenic agents for HER2-altered advanced non-small cell lung cancer: A retrospective real-world study. (ASCO 2023)
This study aimed to assess the effectiveness and safety of pyrotinib plus antiangiogenic agents, including apatinib, anlotinib, and bevacizumab in previously treated patients with HER2-altered advanced NSCLC. Pyrotinib plus antiangiogenic agents demonstrated promising antitumor activity and a manageable safety profile in HER2-altered NSCLC patients.
Retrospective data • Real-world evidence • Real-world • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 exon 20 insertion • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
Avastin (bevacizumab) • Focus V (anlotinib) • AiTan (rivoceranib) • Irene (pyrotinib)
over1year
A nation-wide genomic screening project for further development of targeted therapies in treatment-refractory non–small-cell lung cancer (LC-SCRUM-TRY). (ASCO 2023)
Genotype-matched targeted therapies to overcome treatment-resistance have not been established, except osimertinib against EGFR T790M mutation... LC-SCRUM-TRY contributes to the clinical development of precision medicine to overcome drug resistance, especially for EGFR-mutated NSCLC resistant to EGFR-TKI. This screening platform also help to practice precision medicine for patients initially diagnosed as driver-negative. Clinical trial information: UMIN000041957.
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3)
|
BRAF V600E • EGFR mutation • KRAS G12C • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR T790M • MET exon 14 mutation • EGFR C797S • KRAS G12 • HER-2 exon 20 mutation • EGFR L718Q • EGFR A750P • HER-2 exon 23 mutation
|
Guardant360® CDx • Oncomine Precision Assay
|
Tagrisso (osimertinib)
over1year
Prognostic and predictive implications of plasma ctDNA in guiding first-line targeted therapy for metastatic HER2-mutant non-small cell lung cancer (NSCLC). (ASCO 2023)
55% (17/31) received chemoimmunotherapy with pembrolizumab as the first-line treatment...Additionally, 19% of patients (6/31) received a HER2-targeted antibody-drug conjugates (ADC) as first-line treatment with a median TTD of 6 months (95% CI 2-10), including 5 with T-DM1 and one who received first-line T-DXd treatment with a TTD of 9 months... Baseline plasma ctDNA has the potential to guide first-line targeted therapy for patients with HER2-mutant NSCLC. As an independent negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies to avoid underestimating the effects of therapy.
Clinical • PD(L)-1 Biomarker • IO biomarker • Circulating tumor DNA • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
EGFR mutation • HER-2 mutation • HER-2 exon 20 mutation
|
MSK-IMPACT • MSK-ACCESS • Resolution ctDx Lung Assay™
|
Keytruda (pembrolizumab) • Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki)
over1year
Phase I Beamion Lung 1 trial of BI 1810631, a HER2 tyrosine kinase inhibitor (TKI), as monotherapy in patients (pts) with advanced/metastatic solid tumors with HER2 aberrations: Updated data. (ASCO 2023)
These preliminary data indicate that BI 1810631 is well tolerated and shows encouraging anti-tumor activity in pts with HER2 aberration-positive solid tumors. Recruitment into Phase Ia is ongoing. Updated data, including durability endpoints, will be presented.
Clinical • P1 data • Metastases
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 overexpression • HER-2 amplification • HER-2 mutation • HER-2 exon 20 mutation
|
zongertinib (BI 1810631)
over1year
Comprehensive characterization of 1038 Chinese non-small cell lung cancer patients of different PD-L1 expression levels (AACR 2023)
This study provides a comprehensive analysis of the associations between PD-L1 expression and a multitude of histopathologic, genomic, and immunologic features. Further research is warranted for validation and association of these factors with clinical outcomes.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • KDR (Kinase insert domain receptor) • FAT1 (FAT atypical cadherin 1) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • GNAS (GNAS Complex Locus)
|
PD-L1 expression • TP53 mutation • BRAF V600E • KRAS mutation • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • MET exon 14 mutation • PD-L1 negative • ALK fusion • ALK mutation • ROS1 fusion • MET mutation • KRAS G12 • EGFR positive • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
PD-L1 IHC 22C3 pharmDx
over1year
Neoadjuvant Immunotherapy in Rare Mutations Localized NSCLC (clinicaltrials.gov)
P2, N=30, Recruiting, Guangdong Provincial People's Hospital
New P2 trial
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene)
|
BRAF V600E • HER-2 amplification • HER-2 mutation • MET amplification • RET fusion • MET exon 14 mutation • MET mutation • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
carboplatin • Loqtorzi (toripalimab-tpzi) • albumin-bound paclitaxel • pemetrexed
over1year
HER2 exon 20 insertion mutations and myelosuppression in lung adenocarcinoma patient: a case report and response to trastuzumab deruxtecan. (PubMed, J Cardiothorac Surg)
This was an important case since it exerted effective response to DS-8201. Meanwhile, myelosuppression is also found in the patient, which requires attention to pulmonary symptoms and careful monitoring.
Journal • IO biomarker • HER2 exon 20
|
HER-2 (Human epidermal growth factor receptor 2)
|
EGFR mutation • HER-2 mutation • HER-2 exon 20 insertion • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki)
over1year
Poziotinib in Treatment-Naïve Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-label Phase 2 Trial (Cohort 4). (PubMed, J Thorac Oncol)
Poziotinib demonstrated clinically meaningful efficacy with a manageable toxicity profile for treatment-naïve NSCLC patients harboring HER2 exon 20 mutations.
P2 data • Journal • HER2 exon 20
|
HER-2 (Human epidermal growth factor receptor 2) • TYK2 (Tyrosine Kinase 2)
|
HER-2 mutation • HER-2 exon 20 insertion • HER-2 G778_P780dup • HER-2 exon 20 mutation • HER-2 exon 23 mutation
|
Pozenveo (poziotinib)
over1year
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
over1year
Preclinical activity of BAY 2927088 in HER2 mutant non-small cell lung cancer (AACR 2023)
With the recent approval of fam-trastuzumab deruxtecan-nxki, the first targeted treatment option became available for HER2 mutant NSCLC patients. In addition, the compound was active in a subset of endogenously HER2 mutant cancer cell lines. The in vitro activity of BAY 2927088 was validated in vivo in a patient-derived xenograft model carrying the HER2 exon20 insertion mutation A775insYVMA.The strong preclinical activity of BAY 2927088 in HER2 mutant NSCLC supports clinical evaluation in this indication and might offer a novel targeted therapy option for NSCLC patients that carry HER2 mutations.
Preclinical
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
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EGFR mutation • HER-2 mutation • HER-2 exon 20 insertion • HER-2 L755S • HER-2 S310F • HER-2 exon 20 mutation • HER-2 A775 • HER-2 S335C • HER-2 YVMA • HER-2 exon 23 mutation
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Enhertu (fam-trastuzumab deruxtecan-nxki) • BAY 2927088