Ceritinib
On April 29, 2014, the U. S. Food and Drug Administration granted accelerated approval to ceritinib (ZYKADIA, Novartis Pharmaceuticals Corporation) for the treatment 治療 of patients with anaplastic lymphoma kinase 間變性淋巴瘤激酶 (ALK)-positive 陽性, metastatic 轉移性的 non-small cell lung cancer (NSCLC) with disease progression on 疾病進展 or who are intolerant to crizotinib. 對截克瘤產生抗藥
On March 6, 2013, FDA granted 批准 ceritinib breakthrough therapy designation based on preliminary evidence 初步證據 of clinical 臨床 activity in patients with metastatic ALK-positive NSCLC previously 先前 treated 治療 with crizotinib.
The approval of ceritinib was based on the results of a multicenter, single-arm, open-label clinical trial enrolling a total of 163 patients with metastatic, ALK-positive, NSCLC who had progressed on or were intolerant to crizotinib. All patients received ceritinib at a dose of 750 mg once daily.
The primary endpoint supporting approval was objective response rate (ORR) according to RECIST v1.0 as evaluated by both investigator and a Blinded Independent Central Review Committee (BIRC). Duration of response (DOR) was also assessed.
The median age of patients was 52 years. The majority of patients were female (54%), and White (66%), never or former smoker (97%), had ECOG Performance Status 0 or 1 (87%) and adenocarcinoma histology (93%). Nearly all patients (91%) had disease progression on previous crizotinib and 84% had received two or more prior therapies for metastatic disease. Sites of extra-thoracic metastasis included brain (60%), liver (42%), and bone (42%).
The trial results demonstrated durable responses of large magnitude with an ORR of 44% (95% CI: 36, 52) and DOR of 7.1 months based on BIRC-determined tumor assessments. The analysis by investigator assessment showed similar results with an ORR of 55% (95% CI: 47, 62) and DOR of 7.4 months.
The safety evaluation of ceritinib was based on 255 patients with ALK-positive tumors (246 patients with NSCLC and 9 patients with other cancers) who received ceritinib at a dose of 750 mg once daily. The most common adverse reactions (greater than or equal to 25%) were diarrhea, nausea, transaminitis, vomiting, abdominal pain, fatigue, decreased appetite and constipation. The most common CTCAE Grade 3-4 adverse reactions (greater than or equal to 5%) were diarrhea, fatigue, transaminitis, hyperglycemia, hypophosphatemia, increased lipase levels, and anemia. Additional serious adverse reactions include interstitial lung disease and QT prolongation.
The recommended dose of ceritinib is 750 mg orally once daily on an empty stomach until disease progression or unacceptable toxicity. Approximately 60% of patients initiating treatment at the recommended dose required at least one dose reduction.
http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm395386.htm
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Long term phase 1 data for Ceritinib
Posted on March 15, 2016 by admin
On March 10 an article was published on the long term results of a phase 1 trial of Ceritinib.
The trial enrolled 255 patients from January 2011 and July 2013 of whom 246 had ALK + lung cancer.
Data cutoff was April 2014.
Overall response 總體反應 occurred in 72% of ALK inhibitor naive patients and 56% of ALK inhibitor pretreated patients.
Median duration of response was 17 months in ALK inhibitor naive patients and 8.3 months in pretreated patients.
Brain metastases disease control was 79% in inhibitor naive patients and 65% in ALK pretreated patients.
For more detail, see below.
http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00614-2/abstract
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Ceritinib (Zykadia, LDK378) is one of the first next generation ALK- targeted inhibitors that has been granted 授予an accelerated approval 加速審批 by the FDA for the treatment 治療o f ALK+ metastatic NSCLC patients who experienced 有經驗的 disease 疾病 progression 發展 on, or who are intolerant 不耐 to crizotinib.
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