Two Phase III Studies Evaluating Ceritinib in Patients (Pts) with Anaplastic Lymphoma Kinase (Alk)-Rearranged (Alk+) Non-Small Cell Lung Cancer (Nsclc): Ascend-4 and Ascend-5

摘要: ABSTRACT Background: ALK gene rearrangement occurs in 2–7% of NSCLC cases. Pts with ALK+ respond modestly to chemotherapy, and crizotinib (CRZ) is the only targeted agent currently widely approved for treatment NSCLC. Ceritinib a novel oral inhibitor 20-fold greater potency than CRZ enzymatic assays, sustained activity against both CRZ-resistant CRZ-naive preclinical studies. In phase I clinical study (Shaw et al NEJM 2014), maximum tolerated dose ceritinib was determined be 750 mg/day overall response rate 78 pts treated at this 59%. study, substantial shown CRZ-treated Nausea, vomiting, diarrhea fatigue were most common toxicities. Trial design: Here we describe two III, prospective, multicenter, randomized open-label studies designed compare anti-tumor that chemotherapy adult advanced who are either chemotherapy- (ASCEND-4; NCT01828099) or have received prior (ASCEND-5; NCT01828112). participating trial must stage IIIB IV ≥1 measurable lesion, as defined by Response Evaluation Criteria Solid Tumors (RECIST) version 1.1. will every 21 days (ASCEND-4: pemetrexed 500 mg/m2 combination cisplatin 75 mg/m2 carboplatin AUC 5-6; ASCEND-5: docetaxel 75 mg/m2). The primary objective analysis progression-free survival. Secondary objectives include comparison evaluation survival, rate, duration response, disease control time response. Enrolment ongoing. Disclosure: A. Shaw: Advisory board: Novartis, Pfizer, Ariad, Chugai, Genentech; L. Crino: board honoraria:Novartis; E. Felip: Sat on advisory boards Roche, BMS, BI Lilly; T.S.K. Mok: Employee Chinese University Hong Kong. Research grant: AZ; Ad & Honoraria: AZ, Lilly, Merck Serono, Eisai, AVEO, Taiho, BI, GSK, Clovis, Amgen, Janssen, BioMarin; M. Nishio: Received honoraria from Chugai Novartis; Paz-Ares: Consultant Speakers bureau: Lilly. Bayer, BI; G. Scagliotti: Clovis SB: Lilly Clovis; D.R. Spigel: Consultant: BMS J. Wolf: Hospital Cologne; Boards, speakers bureau research funding: support: Y. Wu: Speaker fees: Sanofi, Pfizer; Castro: P. Sen: of, employee remuneration stock options from: C. Zheng: Cheng Zheng an Joe: Employee, options: Soria: compensated Novartis. All other authors declared no conflicts interest.