About


alecensa

ALEX is a global, Phase III trial evaluating the use of ALECENSA and crizotinib in ALK+ NSCLC.⁷ Results so far confirm nearly three years mPFS with ALECENSA, alongside leading 5-year overall survival rates, as well as favourable safety and tolerability vs crizotinib.^7,8

Study design: A Phase III, multicentre, global, randomised, open-label trial evaluating ALECENSA against crizotinib in treatment-naïve patients with Stage IIIB/IV ALK+ NSCLC.² The primary endpoint was to assess the PFS using RECIST v1.1 (investigator assessment).² Secondary endpoints were independent review committee-assessed PFS, time to CNS progression, objective response rate, and overall survival.² A total of 303 patients were enrolled, 122 patients with CNS metastases and 181 without were included in the clinical trial.²

The updated data (data cut-off: November 30, 2018) confirmed the superior efficacy of ALECENSA with the primary endpoint being met [mature, final ITT stratified mPFS of 34.8 months with ALECENSA vs 10.9 months with crizotinib; HR=0.43 (95% CI: 0.32, 0.58) p<0.0001] and the risk of disease progression or death reduced by 57% (ITT; stratified HR=0.43, 95% CI: 0.32, 0.58).⁸ Even with significantly longer treatment duration with ALECENSA (28.1 months vs 10.8 months), the proportion of patients with Grade 3–5 AEs (52% vs 56%), AEs leading to dose reduction (20% vs 20%) or interruption (26% vs 26%) was similar with ALECENSA vs crizotinib.⁸
 

Additional 12-month follow-up from the final PFS cut-off (November 29, 2019) confirmed clinically meaningful superiority of ALECENSA vs crizotinib in regard to OS rates at 5 years (62.5% [95% CI: 54.3, 70.8] with ALECENSA vs 45.5% [95% CI: 33.6, 57.4] with crizotinib).⁸ The OS benefit of ALECENSA was generally consistent across all patient subgroups with 34.9% and 8.6% of patients remaining on their respective study treatment at cut-off.⁸ OS data for ALECENSA remain immature with 37% of events recorded (stratified HR=0.67 [95% CI: 0.46, 0.98]).⁸ The median duration of follow-up was 48.2 months (range 0.5–62.7) with ALECENSA and 23.3 months (range 0.3–60.6) with crizotinib.⁸ No new safety signals were detected.⁸

The first Phase III randomised trial to evaluate the efficacy and safety of ALECENSA vs crizotinib in Asian patients.⁹
 

This study is the first Phase III randomised trial recruiting only Asian patients to compare ALECENSA with crizotinib as a first-line treatment for ALK+ NSCLC.⁹ This study assessed consistency of the PFS benefit with the global Phase III ALEX study.⁹
 

Study design: A randomised, open-label, Phase III study done at 21 investigational sites in China, South Korea, and Thailand.⁹ 187 Asian patients, aged 18 years or older, with ALK+ NSCLC were randomly assigned to ALECENSA or crizotinib.⁹ Patients with asymptomatic CNS metastases were permitted.⁹ The primary endpoint was investigator-assessed PFS.⁹ The primary analysis population for efficacy was the ITT population, defined as all randomly assigned patients.⁹ The primary analysis population for safety was defined as all patients who received at least one dose of study medication.⁹
 

The data confirmed alignment with the ALEX trial.⁹ Investigator-assessed PFS was significantly prolonged with ALECENSA versus crizotinib (HR=0.22, 95% CI: 0.13, 0.38; p<0.0001).⁹ Independent review committee-assessed PFS was also significantly longer for ALECENSA vs crizotinib group (HR=0.37, 95% Cl: 0.22, 0.61; p<0.0001).⁹ 91% of ALECENSA patients vs 77% crizotinib patients achieved an objective response, with a longer duration of response for ALECENSA than crizotinib (HR=0.22, 95% CI: 0.12, 0.40; p<0.0001).⁹ Time to CNS progression (cause-specific HR=0.14) and the percentage of patients who achieved a CNS objective response with measurable or non-measurable baseline CNS lesions were improved; 73% of ALECENSA patients vs 22% crizotinib patients.⁹ Even with longer treatment duration with ALECENSA than crizotinib (14.7 months vs 12.6 months, respectively), fewer patients had Grade 3–5 (29% vs 48%, respectively) or serious AEs (15% vs 26%, respectively).⁹

The first head-to-head comparison of ALECENSA and crizotinib.¹⁰ 

Based in Japan, this study directly compared the efficacy, safety and tolerability of ALECENSA against crizotinib.¹⁰ For the first time, large-scale findings evidenced superior median PFS in patients receiving ALECENSA vs crizotinib.¹⁰

Study design: A randomised, open-label, Phase III trial in Japanese ALK-inhibitor-naïve patients with ALK+ NSCLC, who were chemotherapy-naïve or had received one previous chemotherapy regimen, at 41 study sites in Japan.¹⁰ Patients were randomly assigned to ALECENSA or crizotinib until progressive disease, unacceptable toxicity, death, or withdrawal.¹⁰ The primary endpoint was PFS assessed by an independent review facility.¹⁰ The efficacy analysis was done in the ITT population, and safety analyses were done in all patients who received at least one study drug dose.¹⁰

At final PFS analysis (data cut-off: June 2018), median PFS was 34.1 months with ALECENSA (95% Cl: 22.1, NE) and 10.2 months (95% CI: 8.3–12.0) with crizotinib.¹¹ 12 ALECENSA patients had discontinued treatment vs 24 in the crizotinib group, due to AEs.¹¹ Grade 3 or 4 events occurred at a greater frequency with crizotinib (60.6%) than ALECENSA (36.9%).¹¹ Dose interruptions due to AEs were also more prevalent with crizotinib than with ALECENSA.¹¹