BC Cancer Protocol Summary for Treatment of ALK-Positive

Advanced Non-Small Cell Lung Cancer (NSCLC) with Ceritinib

Protocol Code: LUAVCER

Tumour Group: Lung

Contact Physician: Dr. Christopher Lee

ELIGIBILITY:
Patients must have:
 Advanced non-small cell lung cancer,
 Laboratory confirmed anaplastic lymphoma kinase (ALK)-positive tumour,
defined as either IHC 3+, FISH positive, or positive by molecular testing (next-
generation sequencing), and
 Disease progression on crizotinib, or intolerance to crizotinib

Patients should have:

 ECOG 0 to 2

Note:
 Sequential ALK targeted therapies (e.g., crizotinib, ceritinib) are not funded
after first-line alectinib,brigatinib, or lorlatinib

EXCLUSIONS:
Patients must not have:
 Congenital long QT syndrome or a persistent corrected electrocardiogram
interval (QTc) of ≥ 500 msec
 Progression during treatment on previous ALK-targeted tyrosine kinase inhibitor

TESTS:
 Baseline: alkaline phosphatase, ALT, total bilirubin, LDH, creatinine,
sodium, potassium, lipase, fasting glucose, ECG
 Baseline, if clinically indicated: C-reactive protein and albumin
 During treatment: alkaline phosphatase, ALT, total bilirubin, and LDH should be
checked two weeks after starting ceritinib and at each subsequent visit
 If clinically indicated: creatinine, lipase, glucose, ECG, sodium, potassium,
heart rate, blood pressure; chest X-ray, CT chest

BC Cancer Protocol Summary LUAVCER Page 1 of 4

Activated: 1 Sept 2018 Revised: 1 May 2024 (Eligibility, exclusions and link in footer updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of
these documents is at your own risk and is subject to BC Cancer’s terms of use available at www.bccancer.bc.ca/terms-of-use
PREMEDICATIONS:
 no premedications required

TREATMENT:
Drug Dose BC Cancer Administration Guideline

ceritinib 450 mg once daily PO with food

Dose reduction:
Dose level -1: 300 mg once daily
Dose level -2: 150 mg once daily
 Careful re-evaluation after initiation of therapy is essential as ceritinib should be
continued only if tumour regression continues or the disease is stable and
cancer-related symptoms have improved. Continued ceritinib for
“psychological” palliation in the face of progressive disease is inappropriate.

DOSE MODICATIONS:
1. Hepatic Dysfunction:
ALT or AST elevation to > 5.0 x ULN Withhold until recovery of AST/ALT to
with total bilirubin ≤1.5 x ULN ≤ 3.0 x ULN or baseline, then resume
at 300 mg daily

ALT or AST elevation to > 3.0 x ULN

and concurrent total bilirubin elevation Permanently discontinue
to > 2 x ULN (in absence of
cholestasis or hemolysis)

2. Pneumonitis: permanently discontinue ceritinib for development of any grade

of treatment-related pneumonitis.
3. QTc Prolongation: treatment interruption and subsequent dose reduction
required for QTc > 500 msec.
4. Bradycardia: for symptomatic, non-life threatening bradycardia, withhold
treatment until asymptomatic or heart rate increases to > 60 bpm. Evaluate
contributing concomitant medications and consider dose reduction when
treatment resumes.
5. Gastrointestinal toxicity: treatment interruption and subsequent dose
reduction required for grade 3 toxicity.
6. Hyperglycemia: treatment interruption and subsequent dose reduction
required for persistent glucose levels > 13.9 mmol/L despite optimal anti-
hyperglycemic therapy.
7. Pancreatic toxicity: treatment interruption and subsequent dose reduction
required for lipase/amylase > 2 x ULN.

BC Cancer Protocol Summary LUAVCER Page 2 of 4

Activated: 1 Sept 2018 Revised: 1 May 2024 (Eligibility, exclusions and link in footer updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of
these documents is at your own risk and is subject to BC Cancer’s terms of use available at www.bccancer.bc.ca/terms-of-use
PRECAUTIONS:
1. Cardiotoxicity: QT interval prolongation and symptomatic bradycardia have
been observed in patients treated with ceritinib. Ceritinib should be
administered with caution in patients with pre-existing or those predisposed to
QTc prolongation, or those who are taking medications that are known to
prolong the QT interval. Caution should be exercised in patients with a low
heart rate at baseline (<60 beats per minute), a history of syncope or
arrhythmia, sick sinus syndrome, sinoatrial block, atrioventricular block,
ischemic heart disease, or congestive heart failure. Concomitant medications
that result in a decrease in heart rate should be avoided if possible during
treatment with ceritinib. Heart rate and blood pressure should be monitored
regularly.
2. Hyperglycemia: ceritinib has been associated with hyperglycemia, with the risk
being higher in patients with diabetes mellitus and/or concurrent steroid use.
Fasting serum glucose should be periodically monitored if clinically indicated
and anti-hyperglycemic medications initiated/optimized as required.
3. Respiratory: ceritinib has been associated with severe, life-threatening or fatal
treatment-related pneumonitis. Patients should be regularly monitored for
pulmonary symptoms indicative of pneumonitis.
4. Pancreatic Toxicity: pancreatitis, including one fatality, has been reported in
less than 1% of patients receiving ceritinib in clinical studies. Monitor lipase and
amylase and observe patients closely for signs and symptoms of pancreatitis.
5. Drug interactions: ceritinib is primarily metabolized via CYP3A. The
concurrent use of strong CYP3A inhibitors may increase ceritinib plasma
concentration and should be avoided. The concurrent use of strong CYP3A
inducers may decrease ceritinib plasma concentration and should be avoided.
6. Hepatic Impairment: as ceritinib is eliminated primarily via the liver, patients
with hepatic impairment may have increased exposure. Use caution in patients
with moderate to severe hepatic impairment.
7. Hepatotoxicity: drug-induced hepatotoxicity has occurred in patients treated
with ceritinib. The majority of cases are manageable and reversible with
treatment interruption and/or dose reduction. Transaminases and bilirubin
should be monitored regularly with more frequent testing following elevations.
8. Gastrointestinal toxicity: gastrointestinal toxicity occurred in 98% of patients,
with a median time onset of 4-8 days. Symptoms are managed with
antidiarrheal agents, antinauseants, and fluid replacement as required.

Contact Dr. Christopher Lee or tumour group delegate at (604) 930-4064 or 1-

800-663-3333 with any problems or questions relating to this treatment
program.

BC Cancer Protocol Summary LUAVCER Page 3 of 4

Activated: 1 Sept 2018 Revised: 1 May 2024 (Eligibility, exclusions and link in footer updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of
these documents is at your own risk and is subject to BC Cancer’s terms of use available at www.bccancer.bc.ca/terms-of-use
References:
1. Novartis Pharmaceuticals Canada Inc. ZYKADIA® product monograph. Dorval, Quebec; 31 August
2016.
2. Shaw AT, Kim DW, Mehra et al. Certinib in ALK-rearranged non-small cell lung cancer. N Engl J Med.
2014; 370 (13): 1189.
3. G Scagliotti, TM Kim, L Crino et al. Certinib vs chemotherapy (CT) in patients (pts) with advanced
anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) previously
treated with CT and crizotinib (CRZ): results from the confirmatory phase 3 ASCEND-5 study.
4. De Castro Jr G, Tan DS, Crino L et al. First-line Ceritinib Versus Chemotherapy in Patients with ALK-
rearranged (ALK+) NSCLC: A Randomized, Phase 3 Study (ASCEND-4) WCLC. 2016; PL03.0.
5. Novartis Pharmaceuticals Corporation. ZYKADIA® full prescribing information. East Hanover, NJ,
USA; June 2017.
6. Novartis Pharmaceuticals Canada Inc. ZYKADIA® product monograph. Dorval, Quebec; 6 January
2020.
7. 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. Journal of Thoracic Oncology. 2019; 14(7): 1255-
1265.
8. Cho BC, Kim D-W, Bearz, A et al. ASCEND-8: A randomized phase 1 study of ceritinib, 450mg or
600mg, taken with a low-fat meal versus 750mg in fasted state in patients with ALK-rearranged
metastatic NSCLC. Journal of Thoracic Oncology. 2017; 12(9): 1357-1367.

BC Cancer Protocol Summary LUAVCER Page 4 of 4

Activated: 1 Sept 2018 Revised: 1 May 2024 (Eligibility, exclusions and link in footer updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of
these documents is at your own risk and is subject to BC Cancer’s terms of use available at www.bccancer.bc.ca/terms-of-use