作者
Jun Tian, Jonathan H Chen, Sherry X Chao, Karin Pelka, Marios Giannakis, Julian Hess, Kelly Burke, Vjola Jorgji, Princy Sindurakar, Jonathan Braverman, Arnav Mehta, Tomonori Oka, Mei Huang, David Lieb, Maxwell Spurrell, Jill N Allen, Thomas A Abrams, Jeffrey W Clark, Andrea C Enzinger, Peter C Enzinger, Samuel J Klempner, Nadine J McCleary, Jeffrey A Meyerhardt, David P Ryan, Matthew B Yurgelun, Katie Kanter, Emily E Van Seventer, Islam Baiev, Gary Chi, Joy Jarnagin, William B Bradford, Edmond Wong, Alexa G Michel, Isobel J Fetter, Giulia Siravegna, Angelo J Gemma, Arlene Sharpe, Shadmehr Demehri, Rebecca Leary, Catarina D Campbell, Omer Yilmaz, Gad A Getz, Aparna R Parikh, Nir Hacohen, Ryan B Corcoran
发表日期
2023/2
期刊
Nature medicine
卷号
29
期号
2
页码范围
458-466
出版商
Nature Publishing Group US
简介
While BRAF inhibitor combinations with EGFR and/or MEK inhibitors have improved clinical efficacy in BRAFV600E colorectal cancer (CRC), response rates remain low and lack durability. Preclinical data suggest that BRAF/MAPK pathway inhibition may augment the tumor immune response. We performed a proof-of-concept single-arm phase 2 clinical trial of combined PD-1, BRAF and MEK inhibition with sparatlizumab (PDR001), dabrafenib and trametinib in 37 patients with BRAFV600E CRC. The primary end point was overall response rate, and the secondary end points were progression-free survival, disease control rate, duration of response and overall survival. The study met its primary end point with a confirmed response rate (24.3% in all patients; 25% in microsatellite stable patients) and durability that were favorable relative to historical controls of BRAF-targeted combinations alone. Single-cell RNA …
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J Tian, JH Chen, SX Chao, K Pelka, M Giannakis… - Nature medicine, 2023