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Ceritinib is a second-generation ALK pill for lung cancer, effective after crizotinib but with gastrointestinal toxicity that limited uptake.
Ceritinib is a second-generation ALK tyrosine kinase inhibitor active against several crizotinib-resistance mutations including L1196M, G1269A, I1171T and S1206Y. The ASCEND-1, 2 and 5 studies established activity after crizotinib, and ASCEND-4 showed first-line superiority over chemotherapy with median progression-free survival of 16.6 versus 8.1 months. It received accelerated US approval in 2014 after crizotinib and full first-line approval in 2017. Gastrointestinal toxicity at the original 750 mg fasting dose limited uptake; the 450 mg dose taken with food improved tolerability with equivalent exposure. It is rarely used now because alectinib, brigatinib and lorlatinib offer better tolerability and CNS control. Ceritinib was proof that resistance to the first ALK drug could be overcome by a more potent one.
Potent ALK inhibitor active against several crizotinib-resistance mutations (L1196M, G1269A, I1171T, S1206Y). Connects to ALK.
1.Ceritinib slips into a pocket on ALK.
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance: how tumours escape each drug class · Lines of therapy.
Oral, self-administered, so it is a Part D drug: covered through a stand-alone Part D plan or Medicare Advantage drug benefit, usually on the specialty tier with 25 to 33% coinsurance until the annual cap ($2,000 in 2025, $2,100 in 2026).
Covered for FDA-labelled and NCCN-listed uses, but almost always behind prior authorisation confirming diagnosis, biomarker and line of therapy; dispensed through a specialty pharmacy.
Part D out-of-pocket capped at $2,000 (2025) / $2,100 (2026). Medicare patients cannot use manufacturer co-pay cards; charity funds (PAN, HealthWell, CancerCare) and the Extra Help subsidy are the routes.
Sources: Medicare.gov: Drug coverage (Part D) · Medicare.gov: Costs for Medicare drug coverage (annual out-of-pocket cap). Not medical or financial advice; verify with your plan.
Sources: NICE TA500 · SMC advice: ceritinib. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
ALK-positive metastatic NSCLC that progressed on or is intolerant to crizotinib
Accelerated approval on a surrogate endpoint, with a confirmatory trial required.
ALK-positive metastatic NSCLC that progressed on or is intolerant to crizotinib
Confirmed: the accelerated approval of 2014 converted to traditional approval 3.1 years after it was granted.
| Region | Year | Indication |
|---|---|---|
| US | 2014 | ALK-positive metastatic NSCLC after crizotinib |
| US | 2017 | First-line ALK-positive metastatic NSCLC |
| EU | 2015 | Conditional May 2015; full approval 2017 |
| England (NICE) | 2018 | Untreated ALK-positive advanced non-small-cell lung cancer · TA500, published 24 January 2018, with the discount agreed in the patient access scheme (ASCEND-4). |
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ASCEND-4 gave ceritinib its 2017 US first-line approval and showed that a second-generation ALK inhibitor beats chemotherapy in untreated disease. In practice alectinib, brigatinib and lorlatinib, tested against crizotinib rather than chemotherapy, became the usual first-line choices, partly because ceritinib's gut side effects at 750 mg fasted were hard to live with.
It made repeat biopsy and genotyping at progression the standard in ALK-positive lung cancer, because after a second-generation inhibitor the presence or absence of an ALK mutation is what separates patients who should receive a third-generation inhibitor from those who should not.
Query for this drug: (TITLE:"Ceritinib" OR ABSTRACT:"Ceritinib" OR TITLE:"Zykadia" OR ABSTRACT:"Zykadia") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Ceritinib, not a curated reading list.
Shares Using Tumor Models to Determine Treatments, Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer, ALK fusion (ALK-positive), Lung cancer drugs in England: what NICE has recommended.
Shares Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer, ALK fusion (ALK-positive), ALK, Small-molecule kinase inhibitors.
Shares Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer, ALK-positive non-small-cell lung cancer, ALK, Non-small-cell lung cancer.
Shares 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, ASCEND-4, Non-small-cell lung cancer.
Shares ASCEND-4, ALK-positive non-small-cell lung cancer, ALK, Lung cancer (all types).
Shares ALK fusion (ALK-positive), ALK-positive non-small-cell lung cancer, ALK, Small-molecule kinase inhibitors.
Shares ASCEND-4, ALK-positive non-small-cell lung cancer, ALK, Lung cancer (all types).
Shares 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, ASCEND-4, Non-small-cell lung cancer.