Ceritinib (Zykadia®)
Drug class: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors
Mechanism of Action
Ceritinib is a tyrosine kinase inhibitor (TKI) that selectively targets anaplastic lymphoma kinase (ALK), a transmembrane receptor involved in cell growth and survival, as well as insulin‑like growth factor‑1 receptor (IGF‑1R), insulin receptor (InsR), and ROS1 (1, 2).
By inhibiting ALK autophosphorylation, ceritinib disrupts downstream signaling pathways, particularly STAT3, thereby suppressing the proliferation of ALK dependent cancer cells. Through selective binding to these receptor sites, ceritinib effectively blocks cell division, tumor growth, angiogenesis, and metastatic spread (1, 2).
Approved Indications
Adults with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) (1)
Dosage and Administration
450 mg orally once daily with food (1)
Key clinical benefits
Improved overall survival (3)
Improved progression-free survival (PFS) (4)
Key clinical trials
ASCEND-4
In this phase III, randomized, open label study, investigators enrolled 376 untreated patients with stage IIIB/IV ALK rearranged non small cell lung cancer (NSCLC). The median progression free survival (PFS) with ceritinib was 16.6 months (95% CI, 12.6–27.2) compared with 8.1 months for chemotherapy (HR: 0.55; 95% CI, 0.42–0.73; p < 0.00001). With maintained health related quality of life (HRQoL), the median overall survival (OS) reached 51.3 months (95% CI, 42.7–55.3).
The most common adverse events (AEs) in the ceritinib group were diarrhea, nausea, vomiting, and elevated alanine aminotransferase, while in the chemotherapy group, nausea, vomiting, and anemia were most frequent. Conducted between August 19, 2013, and May 11, 2015, this study demonstrated the efficacy and safety of ceritinib, supporting its use as a first line therapy for ALK positive NSCLC (3).
ASCEND-5 study
In the phase III ASCEND 5 study, 231 patients with ALK rearranged NSCLC resistant to crizotinib and platinum based chemotherapy were randomized to receive either oral ceritinib (750 mg/day) or chemotherapy (intravenous pemetrexed 500 mg/m² or docetaxel 75 mg/m²). The median progression free survival (PFS) was 9.8 months (95% CI, 4.3–14.0) in the ceritinib arm compared with 1.6 months (95% CI, 1.4–3.0) in the chemotherapy arm. Grade 3–4 adverse events (AEs) occurred in 36.4% of patients receiving ceritinib versus 72.2% in the chemotherapy group.
Ceritinib demonstrated superior efficacy and a more favorable safety profile compared with standard second line chemotherapy in patients previously treated with crizotinib and platinum based regimens (4).
ASCEND-8 Study
In the phase I ASCEND 8 study, 137 patients with advanced ALK positive NSCLC (treatment naïve or previously treated with chemotherapy and/or crizotinib) were enrolled. The trial assessed the pharmacokinetics (PK) and safety of ceritinib at 450 mg or 600 mg with a low fat meal versus 750 mg fasted. Part 2 evaluated efficacy and safety in treatment naïve patients. PK analysis showed that 450 mg with food was comparable to 750 mg fasted, with similar peak plasma concentration and 24 hour exposure. Importantly, the 450 mg with food regimen was associated with fewer gastrointestinal toxicities, with no grade 3–4 events or serious adverse events, establishing a safer dosing profile (5).
In Part 2, 306 patients received ceritinib at 450 mg, 600 mg, or 750 mg. Safety was assessed in 304 patients, and efficacy in 198 treatment naïve patients. The overall response rate (ORR) was 78.1% (95% CI, 66.9–86.9) for 450 mg, 72.5% (95% CI, 58.3–84.1) for 600 mg, and 75.7% (95% CI, 64.3–84.9) for 750 mg. The 450 mg cohort demonstrated the highest median relative dose intensity, the lowest rate of dose reductions, and the lowest incidence of gastrointestinal toxicities (6).
Common Adverse Events
With Ceritinib 450mg:
Diarrhea (1)
Nausea (1)
Abdominal pain (1)
Vomiting (1)
Fatigue (1)
With Ceritinib 750 mg:
All of the above (1)
Decreased appetite (1)
Weight loss (1)
Contraindications / Precautions
Monitor for gastrointestinal adverse reactions: Withhold Ceritinib if unresponsive to antiemetics or antidiarrheals. Resume with dose reduction upon improvement (1).
Risk of Hepatotoxicity, Interstitial Lung Disease/Pneumonitis, QT interval prolongation, Bradycardia, Pancreatitis. Withhold, then reduce dose, or permanently discontinue Ceritinib (1).
Hyperglycemia: Optimize with antihyperglycemic medications (1).
Embryo-Fetal Toxicity: Advise use of contraceptives to avoid embryo-fetal toxicity (1).
Special Notes for Clinician
Clinicians should advise patients not to breastfeed during ceritinib therapy due to potential risks in lactation. Concurrent use of ceritinib should be avoided with strong CYP3A inhibitors or inducers. If unavoidable, reduce the dose of ceritinib. Similarly, avoid coadministration with sensitive CYP3A substrates and CYP2C9 substrates (minimal concentration changes may lead to serious toxicities) (1).
Abbreviations
ALK: anaplastic lymphoma kinase kinase; IGF-1R: insulin-like growth factor 1 receptor; InsR: insulin receptor; AE: adverse event; NSCLC: non-small cell lung cancer; PFS: progression free survival; HR: Hazard ratio; CI: confidence interval.
References
U.S. Food and Drug Administration. Ceritinib – Zykadia® Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211225s000lbl.pdf.
Accessed on 10 September, 2026
De SK. Targeted therapy: small molecules. In: Medicines for Cancer. Elsevier; 2023. p. 205-411.
Soria JC, Tan DS, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. The Lancet. 2017, 4;389(10072):917-29.
Kiura K, Imamura F, Kagamu H, et al. Phase 3 study of ceritinib vs chemotherapy in ALK-rearranged NSCLC patients previously treated with chemotherapy and crizotinib (ASCEND-5): Japanese subset. Jpn J Clin Oncol 2018, 48(4):367-75.
Cho BC, Kim DW, Bearz A, et al. ASCEND-8: A Randomized Phase 1 Study of Ceritinib, 450 mg or 600 mg, Taken with a Low-Fat Meal versus 750 mg in Fasted State in Patients with Anaplastic Lymphoma Kinase (ALK)-Rearranged Metastatic Non-Small Cell Lung Cancer (NSCLC). J Thorac Oncol. 2017, 12(9):1357-1367.
Cho BC, Obermannova R, Bearz A, et al. Efficacy and Safety of Ceritinib (450 mg/d or 600 mg/d) with food versus 750-mg/d fasted in patients with ALK receptor tyrosine kinase (ALK)-positive NSCLC: Primary efficacy results from the ASCEND-8 study. J Thorac Oncol. 2019, 14(7):1255-1265.
About the Author
Jaimee George holds a PhD in Microbiology and has published extensively in peer reviewed journals. As a scientific writer, she has developed systematic reviews, book chapters, review articles, and original research papers. Her professional interests include regulatory writing, medical communication tools, and case report development.
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