Korean Precision Medicine Networking Group study of molecular profiling guided therapy based on genomic alterations in advanced solid tumors (KOSMOS) II (KCSG AL 22-09)

TPS1608 Background: Next-generation sequencing (NGS) has been introduced to many Korean institutions as molecular diagnostics for cancers since 2017, when it was reimbursed by the National Health Insurance Service. However, molecularly-guided treatment (MGT) options based on NGS results have been limited due to the strict regulation for prescribing outside of the approved indication, lack of clinical trial availability, and limited access to molecular tumor boards (MTB) in most institutions. Given our previous KOSMOS study results, which showed MGT was available for 54% (124/198) of patients based on local NGS (ESMO Open 2022;7(6, Suppl 1);100653), KOSMOS-II study was designed to demonstrate MGT would be feasible and effective via a nation-wide precision medicine platform. Methods: This national, prospective, pragmatic, multi-cohort study comprised of a framework to screen pts with metastatic solid tumors for actionable genetic alterations (GA) based on local NGS testing and to recommend MGT by a remote and centralized MTB held weekly or biweekly. MGT can be one of the following options: Tier 1, the therapeutic use of investigational drugs targeting GAs including ALK, EGFR, ERBB2, BRAF, FH, ROS1, RET, or high tumor mutational burden; Tier 2, drugs that are allowed for treatment outside of the approved indications by the National Health Insurance; Tier3, clinical trials matched for GA recommended by MTB. To estimate the proportion of patients receiving MGT to be 50±3.25% with 95% confidence interval, we will enroll 1,000 pts, considering 5% drop-out rate. The clinical benefit rate of MGT beyond 16±2 weeks is the second co-primary endpoint, which is expected to be 30% with type I error of 5% and 90% power. Pts must have progressed ≥ 1 or more lines of therapies; have undergone NGS testing; are able to provide the Variant Call Format (vcf) file of the NGS results. MTB determines clinical actionability of GA and recommends MGT if possible, according to Tier 1,2, or 3. The vcf files and matched clinical information will be deposited to the repository of National Center Center Korea and will be curated in a de-identified clinico-genomic database. As of Feb 2023, 139 of planned 1,000 have been enrolled. Clinical trial information: NCT05525858 .