Pragmatic nationwide master observational trial based on genomic alterations in advanced solid tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II study protocol KCSG AL-22–09
Sun Young Kim,
Jee Hyun Kim,
Tae-Yong Kim,
Sook Ryun Park,
Shinkyo Yoon,
Soohyeon Lee,
Se-Hoon Lee,
Tae Min Kim,
Sae-Won Han,
Hye Ryun Kim,
Hongseok Yun,
Sejoon Lee,
Jihun Kim,
Yoon-La Choi,
Kui Son Choi,
Heejung Chae,
Hyewon Ryu,
Gyeong-Won Lee,
Dae Young Zang,
Joong Bae Ahn
Affiliations
Sun Young Kim
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center
Jee Hyun Kim
Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital
Tae-Yong Kim
Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital
Sook Ryun Park
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center
Shinkyo Yoon
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center
Soohyeon Lee
Department of Internal Medicine, Korea University College of Medicine, Korea University Anam Hospital
Se-Hoon Lee
Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
Tae Min Kim
Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital
Sae-Won Han
Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital
Hye Ryun Kim
Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Yonsei Cancer Center
Hongseok Yun
Center for Genomic Medicine, Seoul National University Hospital
Sejoon Lee
Center for Precision Medicine, Seoul National University Bundang Hospital
Jihun Kim
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center
Yoon-La Choi
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine
Kui Son Choi
Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center
Heejung Chae
Department of Internal Medicine, National Cancer Center
Hyewon Ryu
Division of Hematology and Oncology, Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine
Gyeong-Won Lee
Division of Hematology-Oncology, Department of Internal Medicine, Institute of Health Science, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine
Dae Young Zang
Department of Internal Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital
Joong Bae Ahn
Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Yonsei Cancer Center
Abstract Background Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform. Methods The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment. Discussion This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers. Trial registration NCT05525858.
