Question: What is ceritinib?

Context:
We tested the antitumor activity of the next-generation ALK-TKI ceritinib in the patient with acquired resistance to alectinib. 
The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with ALK-rearranged non-small cell lung cancer (NSCLC).
Both ALK mutations conferred resistance to alectinib as well as to crizotinib, but were sensitive to ceritinib and other next-generation ALK-TKIs. Treatment of the patient with ceritinib led to a marked response.
The ability of ceritinib to overcome alectinib-resistance mutations suggests a potential role for sequential therapy with multiple next-generation ALK-TKIs.
Ceritinib is effective and approved for ALK-positive NSCLC in the acquired resistance setting. 
Ceritinib is an oral, potent, second-generation ALK inhibitor recently approved by the U.S. Food and Drug Administration
Preclinical data showed impressive antitumor activity against crizotinib-resistant clones, and based on available data, ceritinib could represent a suitable option in crizotinib-resistant NSCLC.
In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented.
In particular, ceritinib effectively inhibits ALK harboring L1196M, G1269A, I1171T, and S1206Y mutations, and a cocrystal structure of ceritinib bound to ALK provides structural bases for this increased potency. However, we observed that ceritinib did not overcome two crizotinib-resistant ALK mutations, G1202R and F1174C, and one of these mutations was identified in 5 of 11 biopsies from patients with acquired resistance to ceritinib. Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease.SIGNIFICANCE: The second-generation ALK inhibitor ceritinib can overcome several crizotinib-resistant mutations and is potent against several in vitro and in vivo laboratory models of acquired resistance to crizotinib. 
The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer.
Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease.  The second-generation ALK inhibitor ceritinib can overcome several crizotinib-resistant mutations and is potent against several in vitro and in vivo laboratory models of acquired resistance to crizotinib.
The accelerated approval of potent ALK inhibitors, such as crizotinib and more recently ceritinib (LDK378), based on the well designed phase I/II trials has been a landmark success in clinical cancer research and contributes a new era of oncogenic targeted therapy characterized by elegant clinical trial design. In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented.

Answer: Ceritinib is a second generation tyrosine kinase inhibitor, that serves as an effective and approved oral therapy for patients with ALK-rearranged non-small cell lung cancer.