Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials

RC Doebele; A Drilon; L Paz-Ares; S Siena; AT Shaw; AF Farago; CM Blakely; T Seto; BC Cho; D Tosi; B Besse; SP Chawla; L Bazhenova; JC Krauss; YK Chae; M Barve; I Garrido-Laguna; SV Liu; P Conkling; T John; M Fakih; D Sigal; HH Loong; GL Buchschacher; P Garrido; J Nieva; C Steuer; TR Overbeck; DW Bowles; E Fox; T Riehl; E Chow-Maneval; B Simmons; N Cui; A Johnson; S Eng; TR Wilson; GD Demetri

Journal article

Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials

RC Doebele, A Drilon, L Paz-Ares, S Siena, AT Shaw, AF Farago, CM Blakely, T Seto, BC Cho, D Tosi, B Besse, SP Chawla, L Bazhenova, JC Krauss, YK Chae, M Barve, I Garrido-Laguna, SV Liu, P Conkling, T John Show all

Lancet Oncology | Published : 2020

DOI: 10.1016/S1470-2045(19)30691-6

Abstract

Background: Entrectinib is a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C, which has been shown to have anti-tumour activity against NTRK gene fusion-positive solid tumours, including CNS activity due to its ability to penetrate the blood–brain barrier. We present an integrated efficacy and safety analysis of patients with metastatic or locally advanced solid tumours harbouring oncogenic NTRK1, NTRK2, and NTRK3 gene fusions treated in three ongoing, early-phase trials. Methods: An integrated database comprised the pivotal datasets of three, ongoing phase 1 or 2 clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2), which enrolled patients aged 18 years or older with m..

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University of Melbourne Researchers

Tom John Author

Grants

Awarded by National Cancer Institute

Funding Acknowledgements

The studies were funded by Ignyta and Hoffmann-La Roche. Third-party medical writing assistance, under the direction of the authors, was provided by Charlotte Kennerley and Caroline Loder of Gardiner-Caldwell Communications, Macclesfield, UK, and was funded by F Hoffmann-La Roche. We thank the patients, their families, and the participating study centres. We would also like to acknowledge the investigators of the STARTRK-NG study for the collation of safety data for use in the overall analysis of safety in patients given entrectinib across the three four clinical trials. GD acknowledges the support of the Ludwig Cancer Research, the Adelson Medical Research Foundation, Team Russo, the Rotenberg and Mandelbaum Families, and the Pan Mass Challenge cancer charities (Paul's Posse, Leslie's Links, and Erica's Entourage). EF acknowledges the support of the Alex's Lemonade Stand Foundation.