MET Positivity Not Predictive of Response to Amivantamab-Based Therapy Among Patients With EGFR-Mutant Lung Cancer
MET positivity on immunohistochemistry (IHC) staining was not validated as a biomarker for response to treatment with amivantamab plus lazertinib or amivantamab monotherapy among patients with EGFR-mutant non-small cell lung cancer (NSCLC), following osimertinib treatment.
These data will be presented by Benjamin Besse, MD, PhD, Gustave Roussy Institute, Villejuif, France, at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer in Barcelona, Spain.
This validation analysis included patients in Cohorts E and F from the open-label, phase 1/1b CHRYSALIS-2 study. These cohorts enrolled patients with EGFR exon 19 deletions or L858R-mutated advanced NSCLC. Tumor tissue was collected for IHC staining following progression on osimertinib as the validation of MET positivity as a biomarker. Patients were randomized on a 1-to-1 basis to receive either amivantamab in combination with lazertinib (Cohort E) or as a monotherapy (Cohort F).
The median follow-up duration was 4.5 months. There were 68 in Cohort E and 64 patients in Cohort F that were response-evaluable and had IHC data. Of those patients, 47 (40%) and 10 (31%), respectively, were MET-positive. The confirmed objective response rate (ORR) in Cohort E was 30% among MET-positive patients and 15% among MET-negative. The confirmed ORR in Cohort F was 30% among MET-positive patients and 11% among MET-negative patients. Though ORR were numerically higher among MET-positive patients, prespecified validation criteria were not met in either cohort. The median progression-free survival (PFS) in Cohort E was 6.9 months among MET-positive patients and 4.3 months among MET-negative. In Cohort F, median PFS were 5.6 months and 4.4 months, respectively.
While amivantamab alone or with additional agents are “efficacious for advanced/metastatic NSCLC,” Dr Besse et al concluded, “IHC MET+ was not validated as a biomarker for response to amivantamab-lazertinib or amivantamab monotherapy among participants with EGFR-mutated NSCLC after osimertinib treatment.”
Source:
Besse B, Tomasini P, Cho BC, et al. Validation analysis of MET IHC as a biomarker for amivantamab-lazertinib response in post-osimertinib EGFR-mutant NSCLC. Presented at 2025 World Conference on Lung Cancer. September 6-5, 2025; Barcelona, Spain. Abstract MA07.07
