TPS7583 Background: Molecularly targeted therapies, specifically those directed toward epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangement have improved outcomes in a subset of patients with advanced non-small cell lung cancer (NSCLC). However, the role of molecular testing and targeted therapies for earlier stage disease remains unclear. Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is a National Cancer Institute (NCI) sponsored National Clinical Trials Network (NCTN) initiative to address these unanswered questions. Methods: ALCHEMIST is a clinical trial platform that currently consists of three integrated protocols: ALCHEMIST Screening (A151216; NCT02194738), ALCHEMIST-EGFR (A081105; NCT02193282), and ALCHEMIST-ALK (E4512; NCT02201992). In ALCHEMIST-Screening, up to 8,000 patients with pathologically confirmed stage IB ( ≥ 4 cm)-IIIA non-squamous NSCLC will be enrolled either before or after surgical resection. Tumors will be centrally genotyped for EGFR mutations and ALK rearrangements. Blood and tumor samples will also be collected for advanced genomic analysis at the NCI. Patients with EGFR mutations or ALK rearrangements will be referred to ALCHEMIST-EGFR or-ALK treatment trials, respectively. All other patients will be followed for relapse and survival. Available biopsies at recurrence will be collected to characterize clonal evolution. In the treatment trials, patients will be randomized to placebo vs. erlotinib or crizotinib after completion of standard adjuvant therapy. Treatment will continue for two years. Both trials are double blind studies with a primary endpoint of overall survival (OS). ALCHEMIST-EGFR will enroll 410 patients, which provides 85% power with one-sided type I error rate of 0.05 to demonstrate an OS hazard ratio (HR) of 0.67 favoring erlotinib. ALCHEMIST-ALK will enroll 378 patients to provide 80% power and one-sided type I error of 0.05 to demonstrate an OS HR of 0.67 favoring crizotinib. ALCHEMIST is currently enrolling patients at over 500 centers nationwide. Additional treatment trials for specific molecular subsets may be added in the future. Clinical trial information: NCT02194738.
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<p>The combination treatment of JBJ-04-125-02 and osimertinib do not result in any toxicity issues associated with weight loss but osimertinib at clinically relevant dose (25 mg/kg) is too potent to exhibit additive effect when combined with JBJ-04-125-02.</p>
