TARGET: A Phase II, Open-Label, Single-Arm Study of 5-Year Adjuvant Osimertinib in Completely Resected EGFR-Mutated Stage II to IIIB NSCLC Post Complete Surgical Resection.

Introduction: Osimertinib is a central nervous system (CNS)-active, third generation, irreversible, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits EGFR-TKI sensitizing and EGFR T790M resistance mutations, with demonstrated efficacy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). We present the rationale and design for TARGET (NCT05526755), which will evaluate the efficacy and safety of 5 years of adjuvant osimertinib in patients with completely resected EGFRm stage II to IIIB NSCLC.
Materials and Methods: TARGET is a phase II, multinational, open-label, single-arm study. Adults aged ≥18 years (Taiwan ≥20 years), with resected stage II to IIIB NSCLC are eligible; prior adjuvant chemotherapy is allowed. Eligible patients must have locally confirmed common (exon 19 deletion or L858R) or uncommon (G719X, L861Q, and/or S768I) EGFR-TKI sensitizing mutations, alone or in combination. Patients will receive osimertinib 80 mg once daily for 5 years or until disease recurrence, discontinuation or death. The primary endpoint is investigator-assessed disease-free survival (DFS) at 5 years (common EGFR mutations cohort). Secondary endpoints include: investigator-assessed DFS at 3 and 4 years; overall survival at 3, 4, and 5 years (common EGFR mutations cohort); DFS at 3, 4, and 5 years (uncommon EGFR mutations cohort); safety and tolerability, type of recurrence and CNS metastases (both cohorts). Exploratory endpoints include: tissue/plasma concordance; analysis of circulating molecules in plasma samples using different profiling approaches to detect minimal residual disease; incidence and change over time of incidental pulmonary nodules.
Results: TARGET is currently recruiting, and completion is expected in 2029.
Competing Interests: Disclosure RAS reports research funding from AstraZeneca and Boehringer Ingelheim, and advisory board fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, J INTS BIO, Janssen, Lilly, Merck, Merck Serono, Novartis, Pfizer, Puma, Roche, Taiho, Takeda, Thermo Fisher, Yuhan. FDM reports consultation fees from AstraZeneca, Merck Sharp, & Dohme Oncology, Bristol Myers Squibb, Roche/Genentech, Pfizer, Novartis, and Takeda. JYH reports receiving honoraria from Novartis, Pfizer, Merck, Roche, Janssen, AstraZeneca, and Yuhan, consultation fees from ABION, Janssen, Merck, Novartis, Takeda, Amgen, AstraZeneca, reports grants from Roche, Takeda, ONO, and an advisory board fee from AstraZeneca. JCMH reports speakers’ bureau fees from AstraZeneca, Takeda, Merck Sharp & Dohme, Janssen, Amgen, and Novartis, and advisory board fees from AstraZeneca, Daiichi-Sankyo, Takeda, Merck, Merck Sharp & Dohme, Janssen, Amgen, and Novartis. EM reports employment for AstraZeneca and PHASTAR. LS and MS report employment and stock ownership with AstraZeneca. SP reports paid expert testimony for Merck Serono and Roche, consultation fees from Amgen, AstraZeneca, Bayer, BeiGene, Blueprint, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, EQRx, GlaxoSmithKline, Guardant Health, Janssen, Lilly, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, Seattle Genetics, Takeda, and Turning Point Therapeutics, research funding (to institution) from Amgen, AstraZeneca, Blueprint, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Guardant Health, Janssen, Lilly, Merck Sharp & Dohme, Roche, Takeda, Seattle Genetics, Trizel, Turning Point Therapeutics and member of the board of directors for Mesothelioma Applied Research Foundation.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)