Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase−Positive Non–Small Cell Lung Cancer, A Randomized Clinical Trial

Question Is ensartinib superior to crizotinib for patients with advanced anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC) who have not been treated previously with an ALK inhibitor?
Findings This randomized clinical phase 3 trial including 290 patients met the primary end point; the median progression-free survival was statistically significantly longer with ensartinib than with crizotinib (25.8 vs 12.7 months), and the confirmed intracranial response rate was 64% with ensartinib vs 21% with crizotinib for patients with brain metastases at baseline. Ensartinib had a favorable safety profile.
Meaning Ensartinib represents a new first-line treatment option for patients with ALK-positive NSCLC. READ ARTICLE

JAMA Oncology DOI:10.1001/jamaoncol.2021.3523

Authors: Leora Horn, Ziping Wang, Gang Wu, Elena Poddubskaya, Tony Mok, Martin Reck, Heather Wakelee, Alberto A. Chiappori, Dae Ho Lee, Valeriy Breder, Sergey Orlov, Irfan Cicin, Ying Cheng, Yunpeng Liu, Yun Fan, Jennifer G. Whisenant, Yi Zhou, Vance Oertel, Kim Harrow, Chris Liang, Li Mao, Giovanni Selvaggi and Yi-Long Wu,

Clinical Trials, group3Kirk SmithSeptember 2, 2021ALK, Ensartinib, eXalt3 trial, non-small cell lung cancer (NSCLC)

Ensartinib as Treatment for ALK-Rearranged NSCLC

The eXalt3 trial included 290 ALK-positive, TKI-naïve patients with stage IIIB/IV NSCLC treated with up to one line of prior chemotherapy. Ensartinib demonstrated a significantly improved blinded independent review committee-assessed PFS of 25.8 months compared to crizotinib of 12.7 months, HR 0.51 (95% CI 0.35-0.72, p=0.0001). READ ARTICLE

Oncology Times DOI:10.1097/01.COT.0000721308.30680.3f

Authors: Selina Wong, Amanda Cass and Leora Horn

Clinical TrialsKirk SmithOctober 20, 2020ALK, Ensartinib, NSCLC

Abstract 579: Ensartinib (X-396), a novel ALK TKI, in Chinese ALK-positive non-small cell lung cancer: A phase I, dose-escalation and expansion study

Ensartinib (X-396) is a novel ALK inhibitor with high activity against a broad range of crizotinib-resistant ALK mutations (such as G1269A, F1174, C1156Y, and T1151) and CNS metastases. This Phase I study (NCT02959619) determined the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D), investigated the safety and PK, and explored the clinical efficiency for the compound as monotherapy in Chinese ALK+ NSCLC patients.Patients with advanced ALK+ NSCLC were treated with oral ensartinib (150, 200, 225, or 250 mg once daily) using a conventional 3+3 dose escalation design. The dose-escalation evaluated patients in 28-day cycles. In the dose-expansion phase, ensartinib was given at the recommended dose to further explore PK and clinical efficacy. Treatment was continued until disease progression, or unacceptable toxicity. The study finds ensartinib was well tolerated in Chinese ALK-positive NSCLC patients with high antitumor activity. RP2D was established at 225 mg QD. Ensartini..... READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-579

Authors: Hongyun Zhao, Yuxiang Ma, Yang Zhang, Shaodong Hong, Wenfeng Fang, Yunpeng Yang, Jianjin Huang, Jing Zhao, Yan Huang, Lieming Ding, Li Mao, Giovanni Selvaggi, Li Zhang

Clinical TrialsKirk SmithAugust 1, 2020Ensartinib, X-396, ALK inhibitor, crizotinib, CNS, Chinese, antitumor activity

Abstract 2997: Longitudinal circulating tumor DNA (ctDNA) analysis predicts response and reveals the resistance mechanisms of ensartinib in ALK+ NSCLC patients (pts) progressed on crizotinib

Consistent with previous reports, ensartinib showed high clinical efficacy. Longitudinal ctDNA analysis
could be a powerful tool in predicting treatment outcomes and revealing resistant mechanisms of
ensartinib. We observed G1269A, G1202R and E1210K as the major resistant mutations to ensartinib. READ ARTICLE

Cancer Research DOI:10.1158/1538-7445.AM2020-2997

Authors: Yunpeng Yang, Jie Huang, Tao Wang, Jianya Zhou, Jing Zheng, Jifeng Feng, Wu Zhuang, Jianhua Chen, Jun Zhao, Wei Zhong, Yanqiu Zhao, Yiping Zhang, Yong Song, Yi Hu, Zhuang Yu, Youling Gong, Yuan Chen, Feng Ye, Shucai Zhang, Lejie Cao, Yun Fan, Gang Wu, Yubiao Guo, Chengzhi Zhou, Kewei Ma, Jian Fang, Weineng Feng, Yunpeng Liu, Zhendong Zheng, Gaofeng Li, Ning Wu, Wei Song, Xiaoqing Liu, Shijun Zhao, Lieming Ding, Li Mao, Giovanni Selvaggi, Larry Zhu, Shanshan Xiao, Li Zhang

Clinical TrialsKirk SmithAugust 1, 2020Ensartinib, X-396, ALK inhibitor, post-crizotinib