| Eligibility |
Inclusion Criteria:
- Stage IV (American Joint Committee on Cancer [AJCC] 8th edition) non-small cell lung
cancer with an oncogenic ALK fusion
- Histologies include adenocarcinoma, squamous cell carcinoma, and adenosquamous
adenocarcinoma
- The presence of an oncogenic ALK fusion established from any Clinical Laboratory
Improvement Act (CLIA) certified laboratory
- The patient must belong to one of the following treatment cohorts.
- Cohort 1: Prior 1st generation ALK tyrosine kinase inhibitor (TKI) (crizotinib)
and/or prior 2nd generation TKI (ceritinib, brigatinib, alectinib) and/or
lorlatinib
- Cohort 2: Prior 1st generation ALK TKI (crizotinib) and/or prior 2nd generation
TKI (ceritinib, brigatinib, alectinib) and/or lorlatinib, and platinum-doublet
chemotherapy
- Cohort 3: Prior 1st generation ALK TK (crizotinib) and/or prior 2nd generation
TKI (ceritinib, brigatinib, alectinib) and/or lorlatinib, platinum-doublet
chemotherapy, and any other number of antineoplastic agents (including
immunotherapy, standard or investigational)
- Age = 18
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count (ANC) = 1500/mcL
- Platelets = 100,000/mcL
- Hemoglobin = 9 g/dL without transfusion or erythropoietin (EPO) dependency (within 7
days of assessment)
- Measured or calculated creatinine clearance (CrCl) = 50mL/min (calculated per
Cockcroft-Gault formula)
- Serum total bilirubin = 1.5 X upper limit of normal (ULN) (per institutional
guidelines) OR direct bilirubin = ULN for subjects with total bilirubin levels > 1.5
ULN
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =
2.5 X ULN OR = 5 X ULN for subjects with liver metastases
- Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) = 2.5 X
ULN OR = 5 X ULN for subjects with liver metastases
- Albumin = 2.5g/dL
- Female subject of childbearing potential should have a negative serum pregnancy test
within 21 days of enrollment prior to receiving the first dose of study medication
- Female subjects of childbearing potential must be willing to use a highly effective
method of contraception for the course of the study, through 180 days after the last
dose of study medication. Note: Abstinence is acceptable, if patient documents that
this is their usual lifestyle or preferred contraception method
- Male subjects of childbearing potential must agree to use an adequate method of
contraception starting with the first dose of study therapy through 4 months after the
last dose of study therapy. Note: Abstinence is acceptable, if patient documents that
this is their usual lifestyle or preferred contraception method
- Ability to swallow pills orally and per investigator's assessment, do not have any
significant issues limiting absorption of drug
- Ability to understand and the willingness to sign a written informed consent
- Measurable disease per RECIST v1.1 criteria assessed per screening imaging
- If a cancerous lesion is easily and safely accessible, a pre-treatment biopsy of this
lesion is strongly encouraged but NOT required prior to first dose of gilteritinib.
Archival or fresh tissue biopsy may be used as long as it was obtained prior to cycle
1 day 1 (C1D1)
- At least 7 days must have elapsed since last anti-neoplastic TKI, chemotherapy,
immunotherapy, or investigational agent prior to the first dose of gilteritinib
Exclusion Criteria:
- Received palliative radiation within 7 days of enrollment
- Received prior therapy with a FLT3 inhibitor
- Has a known history of prior malignancy except if the patient has undergone
potentially curative therapy with no evidence of that disease recurrence for 5 years
since initiation of that therapy. Note: the time requirement for no evidence of
disease for 5 years does not apply to the NSCLC tumor for which a subject is enrolled
in the study. The time requirement also does not apply to subjects who underwent
successful definitive resection of basal cell carcinoma of the skin, superficial
bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other
in situ cancers
- Has known active and symptomatic central nervous system (CNS) metastases and/or
carcinomatous meningitis.
- Subjects with previously treated brain metastases may participate provided they
are stable (clinically asymptomatic, and = 2 weeks since completion of treatment)
and are not using steroids for at least 7 days prior to enrollment. A repeat MRI
brain is not necessary to document stability
- Patients with carcinomatous meningitis are excluded regardless of clinical
stability
- If a patient is found to have new/enlarging brain metastases on the screening MRI, the
patient may be monitored closely and radiation could be delayed if the patient has no
symptoms, there is no vasogenic edema, and there is no evidence of midline shift.
- If the patient is symptomatic, there is vasogenic edema, and/or there is midline
shift, the patient will need to undergo treatment for these brain metastases and
meet exclusion criteria #4 exception to treated brain metastases prior to
enrollment. A new MRI brain is NOT required in this situation
- Is pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with informed consent through 180 days after
the last dose of trial treatment
- Has Child-Pugh class C cirrhosis from any cause
- Mean triplicate screening electrocardiogram (EKG) corrected QT (QTc) > 480 ms
- Grade 3 or 4 NYHA (New York Heart Association) congestive heart failure, unless
screening echocardiogram obtained prior to enrollment showed a LVEF (left ventricular
ejection fraction) = 45%
- Surgery within 4 weeks prior to first study dose
- Requires treatment with concomitant drugs that are strong inducers of cytochrome P450
(CYP)3A
- Requires treatment with concomitant drugs that are strong inhibitors or inducers of
P-glycoprotein (P-gp) with the exception of drugs that are considered absolutely
essential for the care of the patient
- Requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine
receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific
receptor, with the exception of drugs that are considered absolutely essential for the
care of the patient
- Active/untreated hepatitis B virus (HBV) or hepatitis C virus (HCV) infection;
patients with treated HBV and HCV are allowed as long as they meet the AST/ALT and
bilirubin criteria
- Known hypersensitivity to gilteritinib or any of the excipients
- Active and clinically significant pancreatitis
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