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Expression of Membrane Targets for Therapeutics in RET-Positive Non–Small Cell Lung Cancer

Abstract

Importance  Patients with advanced RET fusion–positive (RET+) non–small cell lung cancer (NSCLC) who experience disease progression following treatment with RET inhibitors (RETis) have limited treatment options. Identifying membrane protein targets may support the assessment of novel therapies, such as antibody-drug conjugates and bispecific antibodies.

Objective  To evaluate membrane target expression in RET+ NSCLC.

Design, Setting, and Participants  This multicenter cohort study used centralized immunohistochemistry (IHC) on archival tissue samples and whole transcriptome sequencing (WTS) in an independent cohort. Tissue samples were collected from 12 European centers, and WTS was performed on globally sourced patient samples submitted for molecular profiling. This study included samples from patients with RET+ NSCLC and RET–wild-type (RET-wt) adenocarcinoma controls that were analyzed by IHC and 203 RET+ and 19 579 RET-wt samples analyzed by WTS.

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