奥西默替尼
医学
肺癌
内科学
肿瘤科
生物标志物
非小细胞肺癌
T790米
表皮生长因子受体
西妥昔单抗
临床终点
埃罗替尼
吉非替尼
癌症
临床试验
A549电池
生物
结直肠癌
生物化学
作者
Helena A. Yu,Sarah B. Goldberg,Xiuning Le,Zofia Piotrowska,Jonathan W. Goldman,Adrianus J de Langen,Isamu Okamoto,Byoung Chul Cho,Paul D. Smith,Ilhem Mensi,Helen Ambrose,Silvija Kraljevic,Julie Maidment,Juliann Chmielecki,Xiaocheng Li-Sucholeiki,Gail Doughton,Gargi Patel,Phil Jewsbury,P. Szekeres,Jonathan W. Riess
标识
DOI:10.1016/j.cllc.2021.06.006
摘要
Osimertinib, a third-generation, irreversible, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), selectively inhibits both EGFR-TKI sensitizing (EGFRm) and EGFR T790M resistance mutations and has demonstrated efficacy in non-small cell lung cancer (NSCLC) CNS metastases. Most patients with EGFRm NSCLC treated with osimertinib will eventually develop resistance. ORCHARD (NCT03944772) is a phase II study aiming to characterize first-line osimertinib resistance and identify post-progression treatments.Adults aged ≥ 18 years (Japan ≥ 20 years), with EGFRm locally advanced/metastatic NSCLC will be allocated to one of three groups after first-line osimertinib progression, based on molecular profiling from a post-progression tumor biopsy. Group A will evaluate patients with protocol-determined biomarkers of resistance treated with novel osimertinib combination therapies, Group B will evaluate patients without a detectable protocol-determined biomarker treated with non-biomarker selected therapies that are chemotherapy- or EGFR-TKI-based, and Group C (observational) includes patients with histologically transformed disease, and/or a biomarker with an available therapy not investigated in ORCHARD. Group C patients will be treated as per local practice and followed to assess overall survival. The study's platform design allows for adaptability to include emerging treatments related to novel resistance mechanisms. The primary endpoint is confirmed objective response rate (investigator assessed). Other endpoints are progression-free survival, duration of response, overall survival, pharmacokinetics and safety.ORCHARD aims to characterize mechanisms of resistance to first-line osimertinib and explore treatments to overcome acquired resistance. The modular design allows for additional biomarker-directed cohorts and treatment options as understanding of osimertinib resistance mechanisms evolves.
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