dm+d

34215011000001109

New Medicines

AlecensaALK-positive non-small cell lung cancer (NSCLC) - first-line monotherapy

Information

Alecensa
Licence extension / variation
Roche
Roche

Development and Regulatory status

Launched
Launched
Launched
December 2017
Jan 21B-FAST submission using alectinib first-line for ALK-positive non-squamous NSCLC approved in the US [22].
Apr 20Roche pipeline also notes that data from cohort A of the PIII-B-FAST study using alectinib first-line for ALK-positive non-squamous NSCLC has also been filed in the US [19].
Feb 20Filing made to EU for Alecensa in ALK-positive NSCLC; presume these are based on latest data from ALEX study. Filing previously made in Jan 20 to US FDA [19].
Dec 17Approved in EU [16].
Nov 17Approved in the US [15]
Oct 17EU positive opinion for a licence change for use as monotherapy for first-line treatment of adult patients with ALK-positive advanced NSCLC [14].
Sep 17Granted EAMS status in UK for use as monotherapy for first-line treatment of adult patients with ALK-positive advanced NSCLC [13].
Aug 17FDA grants priority review; a decision on approval will be made by 30/11/17 [12].
Mar 17Filed in EU, & rolling submission in US [11].
Oct 16Granted breakthrough therapy status in US for use in patients who haven’t yet been treated with ALK-inhibitor drugs [8].
Jul 16Filings on track for 2017 [7].
Apr 15EU & US filings planned for 2017 [5].
Sep 14First pt enrolled in PIII ALEX trial [4].
Mar 14PIII study to start mid-2014 [2].
Sep 13Awarded breakthrough therapy by the FDA [1].

Category

ALK inhibitor
In 2011, there were 34,889 new cases of lung cancer in England (representing around 47 cases per 100,000 population) , equating to approximately 31,000 cases of NSCLC. ALK-positive disease occurs in approximately 4-5% of NSCLCs (around 1,500 new cases each year).
ALK-positive non-small cell lung cancer (NSCLC) - first-line monotherapy
Oral

Further information

Yes

Trial or other data

May 20Roche announces updated data from the pivotal PIII ALEX study, showing an increased five-year survival rate with alectinib vs. crizotinib, in people living with ALK-positive NSCLC. These data confirm the longer-term efficacy of Alecensa already demonstrated across three phase III clinical trials. The updated results from the ALEX study show a five-year survival rate of 62.5% (95% CI: 54.3-70.8) in the Alecensa treatment group, versus 45.5% (95% CI: 33.6-57.4) with crizotinib.1 Despite longer median treatment duration, the safety profile of Alecensa remains favourable and consistent with previous data, with no new safety signals identified.1 The overall survival (OS) data, which are not yet mature, show a benefit in patients with CNS metastases at baseline (42% reduction in the risk of death versus crizotinib (95% CI: 0.34-1.00)), as well as in those without CNS metastases at baseline (24% reduction in the risk of death versus crizotinib (95% CI: 0.45-1.26)). These data follow on from the final, mature progression-free survival data from the ALEX study, presented at the ESMO congress 2019, which demonstrated a reduced risk of disease worsening or death by 57% (hazard ratio=0.43, 95% CI: 0.32–0.58) with Alecensa vs. crizotinib [20].
Oct 19Final PFS and updated OS data presented at ESMO 2019 [18].
May 18Genentech release follow-up data from PIII ALEX trial. After two years of follow-up, median PFS was 34.8 months in alectinib group vs 10.9 months in crizotinib group (no HR or statistical significance presented) [17].
Jun 17Results of PIII NCT02075840 published in NEJM. RCT (n=303) reported 12-month event-free survival rate of 68.4% with alectinib vs 48.7% with crizotinib; HR 0.47 (P<0.001) [10].
Apr 17Roche announces that the PIII ALEX study met its primary endpoint and showed that alectinib significantly reduced risk of disease worsening or death (progression-free survival, PFS) compared to crizotinib in people with ALK-positive advanced NSCLC. The safety profile of alectinib was consistent with that observed in previous studies, with no new or unexpected adverse events [9].
Jul 16Data from ALEX expected 2017. Recruitment completed Q3 15 [7].
Feb 16Chugai announces that it received a recommendation by an independent data monitoring committee (IDMC) that the J-ALEX study (a PIII study targeting ALK fusion gene positive NSCLC being conducted in Japan) should be stopped early as the study met its primary endpoint at a pre-planned interim analysis. The study showed that patients lived significantly longer without disease worsening (PFS) when treated with Alecensa compared to crizotinib. The J-ALEX study compares efficacy and safety between Alecensa and crizotinib. The J-ALEX study enrolled 207 patients who either had not undergone chemotherapy or had undergone one chemotherapy regimen [6].
Mar 14PIII NCT02075840 = ALEX. First pt expected to be enrolled in Q2 14 [3].
Mar 14NCT02075840 is arandomized, active controlled, multicentre PIII open-label study to evaluate efficacy and safety of alectinib (600mg twice daily) vs critozinib(250mg twice daily) until disease progression in 286 patients with treatment-naive ALK-positive advanced NSCLC. The study is expected to last ~ 42 months. The primary outcome is progression free survival. The study starts Jul 14 and is due to complete Apr 18 [2].

AlecensaALK-positive non-small cell lung cancer (NSCLC) - adjuvant therapy

Information

Alecensa
Licence extension / variation
Roche
Roche

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

ALK inhibitor
In 2011, there were 34,889 new cases of lung cancer in England (representing around 47 cases per 100,000 population) , equating to approximately 31,000 cases of NSCLC. ALK-positive disease occurs in approximately 4-5% of NSCLCs (around 1,500 new cases each year).
ALK-positive non-small cell lung cancer (NSCLC) - adjuvant therapy
Oral