Biomarker analyses
tumor
TUMOR
Given the known heterogeneity of osimertinib resistance, NGS was used to better understand tumor response to the amivantamab and lazertinib regimen and to explore potential biomarkers predictive of response in the osimertinib-relapsed cohort. Patient ctDNA and tumor tissue were available for NGS analysis in 44 of 45 patients and 29 of 45 patients, respectively. Genetic testing of these samples identified 17 patients (38%) who had EGFR-based and/or MET-based osimertinib resistance mutations or amplifications (Fig. Among the 17 patients with EGFR-based and/or MET-based osimertinib resistance, eight achieved a response based on investigator assessment for an ORR of 47% (95% CI, 23–72), with a median duration of response of 10.4 months (95% CI, 2.7–NC). The CBR was 82% (95% CI, 57–96), and the median PFS was 6.7 months (95% CI, 3.4–12.5) (Supplementary Table Of the remaining 28 patients who did not have an identified EGFR-based and/or MET-based osimertinib resistance mechanism, 18 had unknown mechanisms (of these, one had neither tissue nor ctDNA and 13 had ctDNA testing but no tumor testing), and 10 had EGFR-independent and/or MET-independent resistance mechanisms, such as alterations in PIK3CA, KRAS and PTEN, and mutations in cell cycle genes, identified by NGS (Fig. In addition to NGS, an immunohistochemistry (IHC)-based approach was undertaken in patients with sufficient remaining tumor samples (