News - EGFR E709A - LARVOL VERI

10ms

Lazertinib for Patients with NSCLC Harboring Uncommon EGFR Mutations: A Single-Arm, Phase II Multi-Center Trial (IASLC-WCLC 2023)

In this study, we observed the clinical benefit of 240mg Lazertinib in the treatment of naïve EGFR uncommon mutants. Among the mutations, G719X and L861Q showed promising outcomes, which are aligned with preclinical data. The safety profile was consistent with registry trials, indicating the necessity of further exploration for clinical efficacy in uncommon EGFR mutations on a larger scale.

10 months ago

Clinical • P2 data

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR L747S • EGFR E709A

Leclaza (lazertinib)

over1year

Efficacy of EGFR-Tyrosine Kinase Inhibitors for advanced non-small cell lung cancer patients harboring rare EGFR mutations of exon 18 E709X. (PubMed, Med Oncol)

EGFR-tyrosine kinase inhibitors (TKIs) show efficacy against lung cancer, and afatinib has been used as a standard therapy for patients with non-small cell lung cancer (NSCLC) with EGFR rare mutations such as S768I, G719X, and L861Q...New treatment-related adverse events were not observed. NSCLC patients with exon 18 E709X mutations may benefit from treatment with second- or third-generation EGFR-TKIs.

over 1 year ago

Journal

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR exon 18 mutation • EGFR E709A

Gilotrif (afatinib)

almost2years

Audit of Molecular Mechanisms of Primary and Secondary Resistance to Various Generations of Tyrosine Kinase Inhibitors in Known Epidermal Growth Factor Receptor-Mutant Non-small Cell Lung Cancer Patients in a Tertiary Centre. (PubMed, Clin Oncol (R Coll Radiol))

"This study shows the wide spectrum of primary and secondary EGFR resistance mechanisms to first, second and third generation of TKIs and helps us to identify newer therapeutic targets that could carry forward the initial advantage offered by EGFR TKIs."

almost 2 years ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR3 (Fibroblast growth factor receptor 3) • EML4 (EMAP Like 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

KRAS mutation • EGFR mutation • PIK3CA mutation • EGFR L858R • MET amplification • EGFR T790M • EGFR amplification • EGFR exon 20 insertion • MET exon 14 mutation • EGFR C797S • MET mutation • ALK translocation • EGFR exon 20 mutation • EGFR T790M + EGFR C797S • EGFR negative • EGFR E709A

therascreen® EGFR RGQ PCR Kit • Oncomine Focus Assay • Oncomine Lung Cell-Free Total Nucleic Acid Research Assay

Tagrisso (osimertinib) • erlotinib • Gilotrif (afatinib) • gefitinib

2years

NSCLC with uncommon EGFR mutations treated with atezolizumab plus bevacizumab and chemotherapy. (ASCO 2022)

Analysis included 16 stage IV NSCLC patients with uncommon EGFR mutations from 9 different German centers which started treatment in first or further line with Atezolizumab, Bevacizumab, Carboplatin and (nab-)Paclitaxel (ABCP) between October 2018 and January 2022...9 patients received a TKI therapy in first line (4x Afatinib; 5x Osimertinib) with an ORR of 66.7% (CR = 1; PR = 5; SD = 1; PD = 2) and a median time-to-next-treatment of 6.7 months (range: 2.1-39.1 months)... In this retrospective analysis, ABCP achieves an encouraging outcome for patients with uncommon EGFR mutations, comparable to results for common EGFR mutations in IMpower150 (ORR 71%, mPFS: 9.7 months, mOS 29.4 months). This in contrast to immunotherapy alone which shows poor ORR and PFS. Together with new targeted treatment options for Exon 20 insertions like amivantamab (ORR 40%, mPFS 8.3 months) or mobocertinib (ORR 28%, mPFS 7.3 months), ABCP is a valuable option in the early course of treatment for this patient cohort.

2 years ago

PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1)

PD-L1 expression • EGFR mutation • EGFR L861Q • EGFR exon 21 mutation • EGFR G719X • EGFR S768I • EGFR exon 18 mutation • EGFR G719C • EGFR E709A

Avastin (bevacizumab) • Tagrisso (osimertinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • carboplatin • albumin-bound paclitaxel • Rybrevant (amivantamab-vmjw) • Exkivity (mobocertinib)

2years

LU21-16: Lazertinib for Patients With NSCLC Harboring Uncommon EGFR Mutations (clinicaltrials.gov)

P2, N=36, Not yet recruiting, Yonsei University

2 years ago

New P2 trial

EGFR (Epidermal growth factor receptor)

EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR L747S • EGFR E709A

Leclaza (lazertinib)

over2years

[VIRTUAL] Spectrum of Resistance Mechanisms to First, Second and Third Generation Tyrosine Kinase Inhibitors in EGFR Mutant NSCLC Patients (IASLC-WCLC 2021)

Other mutations detected were CTNNB1 D32N, KRAS G12V, and PIK3CA E542K Conclusion Resistance development is unavoidable in EGFR mutant advanced NSCLC on any generation of TKIs. NGS offers an advantage in diagnosing mechanism of resistance for further choice of therapy.

over 2 years ago

Clinical

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

TP53 mutation • KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • PIK3CA mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR T790M • EGFR amplification • EGFR exon 20 insertion • PIK3CA H1047R • KRAS G12V • EGFR C797S • EGFR exon 19 mutation • MET mutation • EGFR exon 19 deletion + EGFR T790M • KRAS G12 • PIK3CA E542K • ALK translocation • EGFR exon 20 mutation • KRAS G13 • BRAF G469A • PIK3CA E542 • KRAS G13C • EGFR H835L • EGFR L833V • PIK3CA exon 9 mutation + HR positive • EGFR E709A • TP53 R213

Oncomine Focus Assay

3years

[VIRTUAL] Primary and secondary resistance mechanisms in first, second and third generation tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer patients. (ASCO 2021)

Primary and secondary acquired resistance is unavoidable in EGFR mutant advanced NSCLC on any generation of TKIs . NGS offers an advantage in diagnosing mechanism of resistance for further choice of therapy.

3 years ago

Clinical

TP53 mutation • KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • PIK3CA mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR T790M • EGFR amplification • EGFR exon 20 insertion • PIK3CA H1047R • KRAS G12V • EGFR C797S • EGFR exon 19 mutation • MET mutation • EGFR exon 19 deletion + EGFR T790M • KRAS G12 • PIK3CA E542K • ALK translocation • EGFR exon 20 mutation • KRAS G13 • BRAF G469A • PIK3CA E542 • KRAS G13C • PIK3CA exon 9 mutation + HR positive • EGFR E709A • TP53 R213

Oncomine Focus Assay

over3years

[VIRTUAL] Prognostic Characteristics and Immunotherapy Response of Non-Squamous NSCLC Patients with KRAS Mutation in East Asian Populations (IASLC-WCLC 2020)

Of them, 6 patients received EGFR TKI treatment (4 gefitinib and 2 erlotinib). Conclusion Kras-G12C mutation was associated with shorter TTR in early-stage NSCLC patients, while Kras-G12V mutation was associated with shorter OS in advanced-stage patients. Kras-G12C was also associated with favorable ICIs treatment effectiveness.

over 3 years ago

Clinical • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase)

KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • EGFR L858R • KRAS G12D • KRAS G12V • ALK fusion • KRAS G12A • EGFR G719S • EGFR mutation + KRAS mutation • KRAS deletion • EGFR E709A

erlotinib • gefitinib