Crizotinib is the current standard of care for NSCLC patients (pts) with ALK+ disease. However, most pts who get crizotinib will progress within a year. Further, until recently, crizotinib was only approved in Europe as 2nd-line treatment after failure of 1st-line platinum-based doublet chemotherapy (PDC), so many pts who relapse after crizotinib have also been pre-treated with PDC. Most will go on to receive standard relapse chemotherapy (SRC), e.g. pemetrexed or docetaxel. The ALK inhibitor alectinib was recently approved by the FDA based on the efficacy/safety shown in two phase 2 single-arm studies of pts with pre-treated ALK+ NSCLC (NP28673: Ou et al, JCO 2015; NP28761: Shaw et al, Lancet Oncol 2016). However, it is not yet confirmed whether this approach would be more or less effective than SRC in the 3rd line for ALK+ NSCLC pts who relapse after both PDC and crizotinib.
ALUR (NCT02604342) is a phase 3 open-label randomised study in pts with advanced or metastatic ALK+ NSCLC and ECOG PS 0–2 who have had one prior line each of PDC and crizotinib. Pts (n = 120) are randomised 2:1 to receive alectinib 600mg BID or SRC (pemetrexed 500mg/m2 q3w or docetaxel, 75mg/m2 q3w; at investigator's discretion) until progression, death or withdrawal. Crossover from SRC to alectinib is permitted on RECIST progression. At the investigators' discretion, alectinib can be continued beyond progression for patients with clinical benefit. FPI was in Oct 2015 and LPI is expected in Q3 2016. The primary endpoint is progression-free survival (PFS) by investigator in the ITT population. Secondary endpoints include objective response rate (ORR) in the central nervous system (CNS) for pts with measurable CNS metastases (mets) at baseline; PFS by independent review committee (IRC); ORR, disease control rate (DCR) and duration of response (DOR) by investigator and IRC; time to CNS progression, CNS DOR and DCR by investigator and IRC; overall survival; health-related quality of life; time to symptom deterioration; and safety. Pts will be stratified by ECOG PS (0/1 vs 2), presence of baseline CNS mets and history of CNS radiation, with caps to ensure ≥50% have baseline CNS mets and both types of SRC are equally represented.
Clinical trial identification
NCT01801111 [NP28673] and NCT01871805 [NP28761].
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd
F. Hoffmann-La Roche Ltd
J. Wolf: Advisory Boards for AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer and Roche. C. Revil: Roche Employee and Stock Ownership. A. Kotb: Employee of Roche. A. Zeaiter: Roche Employee, Stock Ownership and Roche Leadership. All other authors have declared no conflicts of interest.