A phase 3 study to demonstrate whether lorlatinib given as monotherapy is superior to
crizotinib alone in prolonging the progression-free survival in advanced ALK-positive NSCLC
patients who are treatment naïve and to compare lorlatinib to crizotinib with respect to
overall survival in the same population
- Histologically or cytologically confirmed diagnosis of locally advanced or metastatic
ALK-positive NSCLC; at least 1 extracranial measurable target lesion not previously
irradiated. CNS metastases allowed if asymptomatic and not currently requiring
- Availability of an archival FFPE tissue specimen.
- No prior systemic NSCLC treatment.
- ECOG PS 0, 1, or 2.
- Age ≥18 years .
- Adequate Bone Marrow, Liver, Renal, Pancreatic Function
- Negative pregnancy test for females of childbearing potential
- Spinal cord compression unless good pain control attained
- Major surgery within 4 weeks prior to randomization.
- Radiation therapy within 2 weeks prior to randomization, including stereotactic or
partial brain irradiation. Whole brain irradiation within 4 weeks prior to
- Active bacterial, fungal, or viral infection
- Clinically significant cardiovascular disease, active or within 3 months prior to
enrollment. Ongoing cardiac dysrhythmias, uncontrolled atrial fibrillation,
bradycardia or congenital long QT syndrome
- Predisposing characteristics for acute pancreatitis in the last month prior to
- History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial
fibrosis or interstitial lung disease
- Active malignancy (other than NSCLC, non melanoma skin cancer, in situ cervical
cancer, papillary thyroid cancer, LCIS/DCIS of the breast, or localized prostate
cancer) within the last 3 years prior to randomization.
- Concurrent use of any of the following food or drugs within 12 days prior to the first
dose of lorlatinib or crizotinib.
1. known strong CYP3A inhibitors .
2. known strong CYP3A inducers
3. known P gp substrates with a narrow therapeutic index
- Concurrent use of CYP3A substrates with narrow therapeutic indices within 12 days
prior to the first dose of lorlatinib or crizotinib.
- Other severe acute or chronic medical or psychiatric condition, including recent or
active suicidal ideation or behavior, or laboratory abnormality that may increase the
risk associated with study participation or interfere with the interpretation of study
- Investigational site staff members directly involved in the conduct of the study and
their family members, or Pfizer employees, including their family members, directly
involved in the conduct of the study.
- Participation in other studies involving investigational drug(s) within 2 weeks prior
to study entry and/or during study participation.