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Nakamura Y, Komatsu Y, Kato K, et al: bTMB-High Basket trial: A multicenter phase II trial of nivolumab monotherapy in patients with advanced gastrointestinal cancers with high blood tumor mutational burden (bTMB). J Clin Oncol 37, 2019 (suppl; abstr TPS179) Google Scholar Gilson C, Chowdhury S, Parmar MKB, Sydes MR, Investigators S. Incorporating Biomarker Stratification into STAMPEDE: an Adaptive Multi-arm, Multi-stage Trial Platform. Clin Oncol (Royal College of Radiologists (Great Britain)). 2017;29:778–86. BRAF V600 mutations occur in approximately 50% of cutaneous melanomas and result in constitutive activation of downstream signaling through the mitogen-activated protein kinase (MAPK) pathway. 1,2 Vemurafenib (Zelboraf, F. Hoffmann–La Roche/Genentech) is a selective oral inhibitor of the BRAF V600 kinase and is associated with a response rate of approximately 50% and improved survival among patients with BRAF V600E mutation–positive metastatic melanoma. 3 Progress in the areas of genomics, disease pathways, and drug discovery has advanced into clinical cancer research. The latest innovations in clinical trials have followed with master protocols, which are defined by inclusive eligibility criteria and devised to interrogate multiple therapies for a given tumor histology and/or multiple histologies for a given therapy under one protocol. 1, 2 The use of master protocols for oncology has become more common with the desire to improve the efficiency of clinical research and accelerate overall drug development. The LUNG-MAP study, for example, used a master protocol for a phase II/III comparative trial designed to evaluate biomarker-matched therapies in patients with previously treated advanced squamous non–small-cell lung cancer. 3 Shortly after initiation, the US Food and Drug Administration approved a new immunotherapy for the same population. The design’s flexibility facilitated subsequent modification of the standard of care, which preserved the relevance of the study. 1 A second example includes the CREATE study master protocol, which evaluated the efficacy of crizotinib in patients with ALK or MET mutations among six different tumor histologies, where each histology constituted a subtrial of ALK/MET-positive or ALK/MET-negative tumors. 2Hirakawa A, Asano J, Sato H, Teramukai S. Master protocol trials in oncology: Review and new trial designs. Contemp Clin Trials Commun. 2018;12:1–8.

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