NCI MATCH

NCI MATCH
Name	NCI MATCH
Sponsor	National Cancer Institute
Country	United States
Phase	Precision medicine trial
Started	2015
Status	Completed/ongoing arms

NCI MATCH NCI MATCH was a precision oncology clinical trial that tested targeted therapies assigned by tumor molecular profiling rather than cancer histology. It aimed to match adults with solid tumors, lymphomas, or myeloma to agents targeting specific genetic alterations, combining large-scale sequencing with multi-institutional delivery of investigational and approved drugs.

Overview

NCI MATCH brought together stakeholders across National Cancer Institute, National Clinical Trials Network, Alliance for Clinical Trials in Oncology, SWOG Cancer Research Network, Eastern Cooperative Oncology Group, European Society for Medical Oncology, U.S. Food and Drug Administration, American Society of Clinical Oncology, Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, Mayo Clinic, Johns Hopkins Hospital, Stanford Cancer Institute, MD Anderson Cancer Center, University of California Los Angeles Medical Center, Fred Hutchinson Cancer Center, Georgetown University Medical Center, Roswell Park Comprehensive Cancer Center, City of Hope Comprehensive Cancer Center, Vanderbilt-Ingram Cancer Center, Moffitt Cancer Center, Cleveland Clinic, Brigham and Women's Hospital, Hospital of the University of Pennsylvania, Yale Cancer Center, Columbia University Irving Medical Center, Mount Sinai Hospital, Oregon Health & Science University, University of Michigan Rogel Cancer Center, University of Texas Southwestern Medical Center, Massachusetts General Hospital, Seattle Cancer Care Alliance, Dana-Farber/Harvard Cancer Center, Cancer Research UK, Belgian Cancer Registry, Institut Gustave Roussy, Peter MacCallum Cancer Centre, Asia-Pacific Oncology Consortium, National Institutes of Health, American Association for Cancer Research, Bill & Melinda Gates Foundation, Eli Lilly and Company, Roche, Novartis, Pfizer, Merck & Co., AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Genentech, Foundation Medicine.

Trial Design and Methods

The protocol used a master protocol and multiple subprotocols similar to basket trials pioneered in publications from The Cancer Genome Atlas era and modeled after designs discussed at meetings hosted by Institute of Medicine, Cold Spring Harbor Laboratory, Wellcome Trust Sanger Institute, European Molecular Biology Laboratory, Broad Institute, Cambridge University, Harvard Medical School, Yale University School of Medicine, University of Oxford, University of Cambridge Clinical School, Stanford University School of Medicine, Princeton University, Massachusetts Institute of Technology, Imperial College London, Karolinska Institutet, McGill University Health Centre, Karolinska University Hospital, Dana-Farber Cancer Institute workshops. Statistical methods referenced work from Simon–Hayward design adaptations and Bayesian frameworks debated at Joint Statistical Meetings and in journals overseen by editors at Nature Medicine, The Lancet Oncology, Journal of Clinical Oncology, New England Journal of Medicine, Science Translational Medicine, PLoS ONE, Genome Research. Centralized molecular assays were coordinated with commercial partners and academic laboratories including Broad Institute, Foundation Medicine, Genomics England, Beijing Genomics Institute, Roche Diagnostics, Agilent Technologies, Illumina platforms. Data management followed guidance informed by Health Level Seven International, Clinical Data Interchange Standards Consortium, Office for Human Research Protections, National Comprehensive Cancer Network quality metrics.

Eligibility and Enrollment

Eligibility criteria targeted adults with refractory solid tumors, lymphomas, or myeloma after standard therapies, aligning inclusion/exclusion practices found in trials at Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, Mayo Clinic Cancer Center, Stanford Medicine, Vanderbilt University Medical Center, University of California San Francisco Medical Center, Cleveland Clinic Taussig Cancer Institute, Roswell Park Comprehensive Cancer Center. Enrollment pathways included community oncology practices affiliated with the National Cancer Institute Community Oncology Research Program and academic centers. Screening consent processes referenced templates from Office for Human Research Protections, Institutional Review Board practices used at Harvard Medical School and University of Pennsylvania Perelman School of Medicine, with patient navigation services reflecting models from American Cancer Society and Leukemia & Lymphoma Society.

Molecular Testing and Biomarker Matching

Molecular profiling used targeted next-generation sequencing panels and orthogonal assays similar to those deployed by FoundationOne CDx and platforms from Illumina and Thermo Fisher Scientific. Biomarker selection was informed by preclinical and clinical evidence from studies at Broad Institute, Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, Sanger Institute, Cold Spring Harbor Laboratory, and consortia such as The Cancer Genome Atlas. Actionable alterations targeted included mutations in BRAF V600E, amplifications of HER2/ERBB2, fusions involving ALK, rearrangements of ROS1, mutations in KIT, aberrations in PIK3CA, loss of PTEN, alterations in FGFR1, FGFR2, and FGFR3, and mismatch-repair deficiency signals paralleling research from Johns Hopkins University and Mayo Clinic. Companion diagnostics development engaged regulatory science dialogues with U.S. Food and Drug Administration and testing standards from College of American Pathologists.

Treatments and Arms

Treatment arms comprised targeted small molecules, monoclonal antibodies, and kinase inhibitors supplied by pharmaceutical partners including Roche, Novartis, Pfizer, Merck & Co., AstraZeneca, Eli Lilly and Company, Bristol Myers Squibb, Amgen, Takeda Pharmaceutical Company Limited, Sanofi. Arms evaluated agents matched to BRAF, ALK, ROS1, ERBB2, KIT, MET, RET, NTRK fusions, and PI3K/AKT/mTOR pathway components, reflecting precedents from pivotal trials at Vanderbilt-Ingram Cancer Center, Massachusetts General Hospital Cancer Center, Yale Cancer Center, University of Texas MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center. Some arms tested combination regimens inspired by trials at Dana-Farber Cancer Institute and cooperative group studies led by SWOG Cancer Research Network and Alliance for Clinical Trials in Oncology.

Outcomes and Impact

NCI MATCH produced outcome data on objective response rates, progression-free survival, and safety across molecularly selected cohorts, contributing to evidence cited by reviews in Journal of Clinical Oncology, Nature, The Lancet Oncology, and policy discussions at National Cancer Advisory Board. Published outcomes influenced practice at centers like Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, Dana-Farber Cancer Institute, and informed reimbursement deliberations involving Centers for Medicare & Medicaid Services and diagnostic coverage assessments at Blue Cross Blue Shield Association. The trial advanced understanding of tumor-agnostic approvals exemplified by regulatory decisions for agents targeting NTRK fusions and BRAF V600E in multiple histologies.

Ethical, Regulatory, and Funding Considerations

Ethical oversight involved institutional review boards at participating centers such as Johns Hopkins Medicine Institutional Review Board, Massachusetts General Brigham Human Research Committee, UCLA Institutional Review Board, and community site IRBs. Regulatory coordination included interactions with U.S. Food and Drug Administration on companion diagnostics and labeling, and funding combined resources from National Cancer Institute, philanthropic support from Susan G. Komen Foundation-style organizations, and in-kind contributions from pharmaceutical companies. Data sharing and patient privacy were managed under policies influenced by Health Insurance Portability and Accountability Act deliberations and best practices from Global Alliance for Genomics and Health.

Category:Clinical trials