Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial.
oregon; chiles; Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Prospective Studies; Protein Kinase Inhibitors; Mutation; Aniline Compounds; ErbB Receptors
Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) often develop resistance to current standard third-generation EGFR tyrosine kinase inhibitors (TKIs); no targeted treatments are approved in the osimertinib-relapsed setting. In this open-label, dose-escalation and dose-expansion phase 1 trial, the potential for improved anti-tumor activity by combining amivantamab, an EGFR-MET bispecific antibody, with lazertinib, a third-generation EGFR TKI, was evaluated in patients with EGFR-mutant NSCLC whose disease progressed on third-generation TKI monotherapy but were chemotherapy naive (CHRYSALIS cohort E). In the dose-escalation phase, the recommended phase 2 combination dose was established; in the dose-expansion phase, the primary endpoints were safety and overall response rate, and key secondary endpoints included progression-free survival and overall survival. The safety profile of amivantamab and lazertinib was generally consistent with previous experience of each agent alone, with 4% experiencing grade ≥3 events; no new safety signals were identified. In an exploratory cohort of 45 patients who were enrolled without biomarker selection, the primary endpoint of investigator-assessed overall response rate was 36% (95% confidence interval, 22-51). The median duration of response was 9.6 months, and the median progression-free survival was 4.9 months. Next-generation sequencing and immunohistochemistry analyses identified high EGFR and/or MET expression as potential predictive biomarkers of response, which will need to be validated with prospective assessment. ClinicalTrials.gov identifier: NCT02609776 .
Cho, Byoung Chul; Kim, Dong-Wan; Spira, Alexander I; Gomez, Jorge E; Haura, Eric B; Kim, Sang-We; Sanborn, Rachel E; Cho, Eun Kyung; Lee, Ki Hyeong; Minchom, Anna; Lee, Jong-Seok; Han, Ji-Youn; Nagasaka, Misako; Sabari, Joshua K; Ou, Sai-Hong Ignatius; Lorenzini, Patricia; Bauml, Joshua M; Curtin, Joshua C; Roshak, Amy; Gao, Grace; Xie, John; Thayu, Meena; Knoblauch, Roland E; and Park, Keunchil, "Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial." (2023). Articles, Abstracts, and Reports. 7873.