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The NCI-MATCH trial: lessons for precision oncology

Abstract

The NCI-MATCH (Molecular Analysis for Therapy Choice) trial (NCT02465060) was launched in 2015 as a genomically driven, signal-seeking precision medicine platform trial—largely for patients with treatment-refractory, malignant solid tumors. Having completed in 2023, it remains one of the largest tumor-agnostic, precision oncology trials undertaken to date. Nearly 6,000 patients underwent screening and molecular testing, with a total of 1,593 patients (inclusive of continued accrual from standard next-generation sequencing) being assigned to one of 38 substudies. Each substudy was a phase 2 trial of a therapy matched to a genomic alteration, with a primary endpoint of objective tumor response by RECIST criteria. In this Perspective, we summarize the outcomes of the initial 27 substudies in NCI-MATCH, which met its signal-seeking objective with 7/27 positive substudies (25.9%). We discuss key aspects of the design and operational conduct of the trial, highlighting important lessons for future precision medicine studies.

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Fig. 1: NCI-MATCH platform trial design.

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All authors made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; assisted in drafting the article and/or revising it critically for important intellectual content; and approved the final version to be published.

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Correspondence to Peter J. O’Dwyer.

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Competing interests

P.J.O.’D. received research support from Pfizer, Genentech, BMS, AstraZeneca, GSK, Five Prime, FortySeven, Merck, Syndax, BBI, Novartis, Celgene, Incyte, Lilly/Imclone, array, h3biomedicine, Taiho, Minneamrata, pharmacyclics/abbvie and Mirati; and provided expert testimony for Dai-ichi Sankyo. K.T.F. has served on the board of directors of Loxo Oncology, Clovis Oncology, Strata Oncology, Checkmate Pharmaceuticals, Kinnate Pharmaceuticals and Scorpion Therapeutics; on the scientific advisory boards of PIC Therapeutics, Apricity, Oncoceutics, Fog Pharma, Tvardi, xCures, Monopteros, Vibliome, ALX Oncology, OMRx, Soley Therapeutics and Quanta Therapeutics; as a consultant to Lilly, Novartis, Genentech and Takeda; and received research funding from Novartis and Sanofi. A.J.I. holds stock options in, and has served on the scientific advisory boards of, PAIGE.AI, Kinnate Biopharma, Repare Therapeutics and SequreDx, and has received research support from Invitae. C.A. serves or has served as a scientific advisor to Novartis, Lilly, Merck, AstraZeneca, Daiichi Sankyo, Sanofi, TAIHO Oncology, PUMA Biotechnology, OrigiMed, Arvinas and the Komen Foundation; received grant support from Pfizer, Lilly and Takeda; and holds minor stock options in Provista Diagnostics. The remaining authors report no competing interests.

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O’Dwyer, P.J., Gray, R.J., Flaherty, K.T. et al. The NCI-MATCH trial: lessons for precision oncology. Nat Med 29, 1349–1357 (2023). https://doi.org/10.1038/s41591-023-02379-4

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