udy A2201 involved 140 patients who had been previously treated with 1-3 lines of cytotoxic chemotherapy followed by treatment with crizotinib, and who had then progressed on crizotinib. The median age was 51 years (range: 29-80 years); 87.1% of patients were younger than 65 years and 50.0% were female. The majority of patients were Caucasian (60.0%) or Asian (37.9%). 92.1% of patients had adenocarcinoma.
The main efficacy data for both studies are summarised in Table 6. Final overall survival (OS) data are presented for Study A2201. For Study X2101, OS data were not yet mature at the time of the analysis.
Table 6 ALK-positive advanced NSCLC - overview of efficacy results from Studies X2101 and A2201
Study X2101
ceritinib 750 mg
N=163
Study A2201
ceritinib 750 mg
N=140
Duration of follow-up
Median (months) (min – max)
10.2
(0.1 – 24.1)
14.1
(0.1 – 35.5)
Overall response rate
Investigator (95% CI)
56.4% (48.5, 64.2)
40.7% (32.5, 49.3)
BIRC (95% CI)
46.0% (38.2, 54.0)
35.7% (27.8, 44.2)
Duration of response*
Investigator (months, 95% CI)
8.3 (6.8, 9.7)
10.6 (7.4, 14.7)
BIRC (months, 95% CI)
8.8 (6.0, 13.1)
12.9 (9.3, 18.4)
Progression-free survival
Investigator (months, 95% CI)
6.9 (5.6, 8.7)
5.8 (5.4, 7.6)
BIRC (months, 95% CI)
7.0 (5.7, 8.7)
7.4 (5.6, 10.9)
Overall survival (months, 95% CI)
16.7 (14.8, NE)
15.6 (13.6, 24.2)
NE = not estimable
Study X2101: Responses assessed using RECIST 1.0
Study A2201: Responses assessed using RECIST 1.1
*Includes only patients with confirmed CR, PR
In Studies X2101 and A2201, brain metastases were seen in 60.1% and 71.4% of patients, respectively. The ORR, DOR and PFS (by BIRC assessment) for patients with brain metastases at baseline were in line with those reported for the overall population of these studies.
Non-adenocarcinoma histology
Limited information is available in ALK-positive NSCLC patients with non-adenocarcinoma histology.
Elderly
Limited efficacy data are available in elderly patients. No efficacy data are available in patients over 85 years of age.
Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with Zykadia in all subsets of the paediatric population in lung carcinoma (small cell and non-small cell carcinoma) (see section 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
Absorption
Peak plasma levels (Cmax) of ceritinib are achieved approximately 4 to 6 hours after a single oral administration in patients. Oral absorption was estimated to be ≥25% based on metabolite percentages in the faeces. The absolute bioavailability of ceritinib has not been determined.
Systemic exposure of ceritinib was increased when administered with food. Ceritinib AUCinf values were approximately 58% and 73% higher (Cmax approximately 43% and 41% higher) in healthy subjects when a single 500 mg ceritinib dose was administered with a low fat meal (containing approximately 330 kcalories and 9 grams of fat) and a high fat meal (containing approximately 1000 kcalories and 58 grams of fat), respectively, as compared with the fasted state.
In a dose optimisation study A2112 (ASCEND-8) in patients comparing Zykadia 450 mg or 600 mg daily with food (approximately 100 to 500 kcalories and 1.5 to 15 grams of fat) to 750 mg daily under fasted conditions (dose and food condition of adm |
