Amivantamab Plus Lazertinib in Patients With EGFR-mutant Non-small Cell Lung Cancer (NSCLC) After Progression on Osimertinib and Platinum-based Chemotherapy: Results From CHRYSALIS-2 Cohort A.

Introduction: Treatment options for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with disease progression on/after osimertinib and platinum-based chemotherapy are limited.

Methods: CHRYSALIS-2 Cohort A evaluated amivantamab+lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on/after osimertinib and platinum-based chemotherapy. Primary endpoint was investigator-assessed objective response rate (ORR).

Intratumor heterogeneity of EGFR expression mediates targeted therapy resistance and formation of drug tolerant microenvironment.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used to treat non-small cell lung cancers with EGFR mutations, but drug resistance often emerges. Intratumor heterogeneity is a known cause of targeted therapy resistance and is considered a major factor in treatment failure. This study identifies clones of EGFR-mutant non-small cell lung tumors expressing low levels of both wild-type and mutant EGFR protein.

Sunvozertinib monotherapy in EGFR tyrosine kinase inhibitor-resistant non-small cell lung cancer with EGFR mutations.

Background: Multiple agents can be used to treat patients with EGFR mutated non-small cell lung cancer (NSCLC) who develop resistance to EGFR tyrosine kinase inhibitors (TKIs), but the clinical outcome was not satisfactory, especially in patients with multiple lines of prior therapies. Therefore, there is an unmet medical need for these patients. Sunvozertinib is an oral, potent, irreversible, and mutant-selective EGFR TKI targeting EGFR mutations with weak activity against wild-type EGFR.

Biochemical analysis of EGFR exon20 insertion variants insASV and insSVD and their inhibitor sensitivity.

Somatic mutations in the epidermal growth factor receptor (EGFR) are a major cause of non-small cell lung cancer. Among these structurally diverse alterations, exon 20 insertions represent a unique subset that rarely respond to EGFR tyrosine kinase inhibitors (TKIs). Therefore, there is a significant need to develop inhibitors that are active against this class of activating mutations.