How ALECENSA works

ALECENSA is a highly selective and potent tyrosine kinase inhibitor of Anaplastic Lymphoma Kinase (ALK).

ALK is a tyrosine kinase that is activated following gene mutations, and promotes growth and survival in certain cancers. Abnormal forms of ALK are found in 5% of cases of non-small cell lung cancer (NSCLC).

Inhibition of ALK activity with ALECENSA has been shown to block downstream signalling pathways, including STAT 3 and PI3K/AKT, and induce tumour cell death.

Alecensa Mechanism of Action

Setting the treatment standard in
1L ALK+ NSCLC

A wealth of evidence

ALECENSA has been thoroughly investigated in 3 phase III clinical trials, demonstrating proven efficacy and safety as 1L monotherapy

  • ALEX trial

    The largest ongoing clinical study into the efficacy and safety of ALECENSA vs crizotinib.

    ALEX is a global phase III trial currently evaluating the use of ALECENSA and crizotinib in ALK+ NSCLC. Results so far confirm nearly 3 years mPFS with ALECENSA, alongside leading 5 year overall survival rates, as well as favourable safety and tolerability vs crizotinib.

    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. The primary endpoint was to assess the PFS using RECIST v1.1 (investigator assessment). Secondary endpoints were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival. A total of 303 patients were enrolled, 122 patients with CNS metastases and 181 without were included in the clinical trial.

    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 34.8m with ALECENSA vs 10.9m 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). Despite significantly longer treatment duration with ALECENSA (27.7m vs 10.8m), the proportion of patients with grade 3–5 adverse events (AEs) (49% vs 55%), AEs leading to dose reduction (19% vs 20%) or interruption (25% vs 26%) was lower with ALECENSA vs crizotinib.

    Additional 12-month follow-up from the final PFS cut-off (19 November 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). 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. OS data for ALECENSA remain immature with 37% of events recorded (stratified HR 0.67, 95% CI: 0.46, 0.98). 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. No new safety signals were detected.

  • ALESIA trial

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

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

    This study is the first phase 3 randomised trial recruiting only Asian patients to compare ALECENSA with crizotinib as a first-line treatment for ALK-positive NSCLC. This study assessed consistency of the progression-free survival benefit with the global phase III ALEX study.

    Study design: A randomised, open-label, phase III study done at 21 investigational sites in China, South Korea, and Thailand. 187 Asian patients, aged 18 years or older, with ALK-positive non-small-cell lung cancer were randomly assigned  to ALECENSA or crizotinib. Patients with asymptomatic CNS metastases were permitted. The primary endpoint was investigator-assessed progression-free survival. The primary analysis population for efficacy was the intention-to-treat population, defined as all randomly assigned patients. The primary analysis population for safety was defined as all patients who received at least one dose of study medication.

    The data confirmed alignment with the ALEX trial. Investigator-assessed progression-free survival was significantly prolonged with ALECENSA versus crizotinib (HR 0.22, 95% CI: 0.13, 0.38). Independent review committee-assessed progression-free survival was also significantly longer for ALECENSA vs crizotinib group (HR 0.37, 95% Cl: 0.22, 0.61). 91% of ALECENSA patients vs 77% crizotinib achieved an objective response, with a longer duration of response for ALECENSA than crizotinib (HR 0.22, 95% CI: 0.12, 0.40). 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. Despite longer treatment duration with ALECENSA than crizotinib (14.7 months vs 12.6 months), fewer patients had grade 3–5 (29% vs 48%) or serious AEs (15% vs 26%).

  • J-ALEX trial

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

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

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

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

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

ALECENSA phase III trials

Key findings from ALEX

The guideline-preferred 1L treatment

Through the wealth of clinical data, ALECENSA is the preferred 1L treatment in 2 international guidelines

ESMO

European Society for Medical Oncology – Europe's leading medical oncology society

NCCN

The National Comprehensive Cancer Network – evidence-based cancer guidelines

ALK+ NSCLC guidelines

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Real-world experience