Anti-Tumor Activity of Alectinib in Crizotinib Pre-Treated Alk-Rearranged Nsclc in Jp28927 Study

Abstract

ABSTRACT Aim: Alectinib is a CNS-penentrant, highly selective ALK inhibitor with a novel scaffold. JP28927 is a clinical pharmacological study to evaluate the bioequivalence of alectinib 300 mg b.i.d. with 20 and 40 mg capsules (caps) vs. 150 mg caps and food effect with 150mg caps in ALK-rearranged NSCLC patients (pts), regardless of history of previous ALK inhibitor treatment. Results for bioequivalence, food effect, efficacy and safety were reported at ASCO2014. ALK-rearranged NSCLC pts had to discontinue treatment from crizotinib, a first generation ALK inhibitor, because of drug resistance or intolerance. Methods: 35 ALK-rearranged NSCLC pts were enrolled into JP28927 study. Pts continued alectinib 300 mg b.i.d. with 150 mg caps until the investigator determined lack of clinical benefit. This report describes the updated efficacy and safety data for alectinib in 28 crizotinib pre-treated NSCLC pts included in JP28927. Results: As of Jan 11, 2014, median follow-up duration was 141 days (range: 35-166) and 21 pts continued treatment with alectinib without progressive disease (PD). Among 24 pts with target lesions, tumor shrinkage of more than 30 % was observed in 18 pts. Confirmed response rate was 58.3% (95%CI: 36.6-77.9) and disease control rate was 83.3 % (95%CI: 62.6-95.3) by investigator assessment. 19 of 28 pts had brain metastases at baseline, and 6 pts had no prior brain irradiation. 13 pts with brain metastases, including 4 pts without prior brain irradiation, were still on study treatment without PD. The safety profile was favorable, and continued the same trend previously reported. No pts discontinued study treatment for a safety reason. Gastrointestinal and visual disorders, characteristic of crizotinib treatment, were mild and not so frequent with alectinib. Conclusions: Alectinib showed promising response, including in brain metastases, and good tolerability in crizotinib pre-treated pts. These findings suggest that alectinib is a novel therapeutic option for crizotinib pre-treated ALK-rearranged NSCLC. Disclosure: T. Seto: Other substantive relationships: Honoraria (Chugai Pharmaceutical Co., Ltd., Pfizer Japan Inc., Novartis Pharma K.K.), Research funding(Chugai Pharmaceutical Co., Ltd., Pfizer Japan Inc., Novartis Pharma K.K., Astellas Pharma Inc.); T. Hida: Corporate sponsored research: Chugai, Pfizer, Novartis; K. Nakagawa: Advisory board: Abbott Japan Co., Ltd. Astellas Pharma Inc. Chugai Pharmaceutical Co.,Ltd. Pfizer Japan Inc.Novartis Pharma K.K. Corporate sponsored research:Chugai Pharmaceutical Co.,Ltd.Pfizer Japan Inc.Novartis Pharma K.K.; M. Satouchi: Corporate sponsored research:Chugai, Pfizer, Novartis Other substantive relationships:Honoraria; Chugai, Pfizer, Novartis; M. Nishio: Corporate sponsored research:Chugai, Novartis, Pfizer Other substantive relationships:Honoraria; Chugai, Novartis, Pfizer; K. Hotta: Corporate sponsored research: Chugai Other substantive relationships:Honoraria; Chugai, Pfizer; H. Murakami: Corporate sponsored research:Chugai, Novartis, Astellas; Y. Ohe: Corporate sponsored research: Chugai, Pfizer Other substantive relationships: Honoraria; Chugai, Pfizer; K. Takeda: Other substantive relationships: Chugai, Pfizer, Novartis; M. Tatsuno: Chugai employee; T. Shimada: Chugai employee; T. Tanaka: Chugai employee; T. Tamura: Corporate sponsored research: Chugai, Astellas, AbbVie (Abbott) Other substantive relationships: Honoraria; Chugai, Astellas, Novartis.