FDA Approval for Ceritinib
Brand name(s): Zykadia™
- Approved for previously treated ALK-positive metastatic non-small cell lung cancer
Full prescribing information is available, including clinical trial information, safety, dosing, drug–drug interactions, and contraindications.
On April 29, 2014, the Food and Drug Administration (FDA) granted accelerated approval to ceritinib (Zykadia™, made by Novartis Pharmaceuticals Corporation) for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who experience disease progression on or who are intolerant to crizotinib (Xalkori®).
The approval of ceritinib was based on the results of a multicenter single-arm open-label clinical trial enrolling 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 as evaluated by both the clinical trial investigator and a blinded independent central review committee (BIRC). Duration of response was also assessed.
The median age of the patients was 52 years. The majority of patients were female (54 percent), white (66 percent), and either a never or former smoker (97 percent). Most had an ECOG performance status of 0 or 1 (87 percent) and adenocarcinoma histology (93 percent). Nearly all patients (91 percent) had disease progression on previous crizotinib therapy, and 84 percent had received two or more previous therapies for metastatic disease. Sites of extra-thoracic metastasis included the brain (60 percent), liver (42 percent), and bone (42 percent).
The trial results demonstrated durable responses of large magnitude, with an ORR of 44 percent (95 percent CI: 36, 52) and a duration of response of 7.1 months based on BIRC-determined tumor assessments. The investigator analyses showed similar results, with an ORR of 55 percent (95 percent CI: 47, 62) and a response duration 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 (at least 25 percent) were diarrhea, nausea, elevated liver enzymes (transaminases), vomiting, abdominal pain, fatigue, decreased appetite, and constipation. Severe adverse reactions (grade 3-4 according to Common Terminology Criteria for Adverse Events) that occurred in at least 5 percent of patients were diarrhea, fatigue, elevated transaminases, high blood sugar, low blood phosphorus levels, increased lipase levels, and anemia. Additional serious adverse reactions included interstitial lung disease and abnormal heartbeat (QT prolongation).
The FDA granted ceritinib breakthrough therapy designation in March 2013 based on preliminary evidence of clinical activity in patients with metastatic ALK-positive NSCLC who had been previously treated with crizotinib.
The recommended dose of ceritinib is 750 mg orally once daily on an empty stomach until disease progression or unacceptable toxicity. Approximately 60 percent of patients initiating treatment at the recommended dose required at least one dose reduction.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Office of Hematology and Oncology Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.