| General information |
| Database: | DB00070 |
| Objective: | non small cell lung cancer (non small cell lung cancer) harboring the anaplastic lymphoma kinase gene (ALK) rearrangement is sensitive to the ALK inhibitor crizotinib, but resistance invariably develops. Ceritinib (LDK378) is a new ALK inhibitor that has shown greater antitumor potency than crizotinib in preclinical studies. |
| Authors: | Shaw AT, et al |
| Title: | Ceritinib in ALKrearranged non small cell lung cancer. |
| Journal: | N Engl J Med. |
| Year: | 2014 |
| PMID: | 24670165 |
| Trial Design |
| Clinical Trial Id: | NCT01283516 |
| Agent: | ceritinib
|
| Target: | ALK
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase I |
| Key Patients Feature: | patients with non small cell lung cancer who had had disease progression during treatment with crizotinib |
| Biomarker: | ALKpositive |
| Biomark Analysis: | Responses were observed in patients with various resistance mutations in ALK and in patients without detectable mutations. |
| Control Group Info: | single arm |
| Treatment Info: | they administered oral ceritinib in doses of 50 to 750 mg once daily to patients with advanced cancers harboring genetic alterations in ALK. In an expansionphase of the study, patients received the maximum tolerated dose. |
| Primary End Point: | MDT, DLT, toxicity |
| Secondary End Point: | NA |
| Patients Number: | 130 |
| Trial Results |
| DLT_MTD: | The maximum tolerated dose of ceritinib was 750 mg once daily; doselimiting toxic events included diarrhea, vomiting, dehydration, elevated aminotransferase levels, and hypophosphatemia. |
| Objective Response Rate: | as fisrtline:58%, as secondline:56% |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | PFS among pts who received at least 400 mg of ceritinib/d:7 months (95% CI, 5.6 to 9.5). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | diarrhea, vomiting, dehydration, elevated aminotransferase levels, and hypophosphatemia |
| Conclusions: | Ceritinib was highly active in patients with advanced, ALKrearranged non small cell lung cancer, including those who had had disease progression during crizotinib treatment, regardless of the presence of resistance mutations in ALK. |