Inclusion Criteria:

          -  Participants must have evidence of histologically or cytologically confirmed diagnosis
             of metastatic NSCLC (Stage IV, American Joint Committee on Cancer [AJCC] v7.0) that
             carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA)
             approved fluorescence in situ hybridization (FISH) assay (Abbott Molecular Inc) or by
             Immunohistochemistry (IHC) (Ventana Inc).

          -  Disease Status Requirements: disease progression after alectinib or ceritinib as first
             line therapy (the study will limit enrollment of participants with best response of
             progression or indeterminate on prior alectinib to 8 participants). Participants may
             have had prior chemotherapy, but only if before starting treatment with alectinib or
             ceritinib.

          -  Tumor Requirements: All Participants must have at least one measurable target
             extracranial lesion according to RECIST v1.1. Participants with asymptomatic CNS
             metastases (including participants controlled with stable or decreasing steroid use
             within the last 2 weeks prior to study entry) will be eligible. Participants who have
             leptomeningeal disease (LM) or carcinomatous meningitis (CM) will be eligible if the
             LM/CM is visualized on magnetic resonance imaging (MRI) or if documented baseline
             cerebral spinal fluid (CSF) positive cytology is available.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

          -  Adequate bone marrow functioning, pancreatic function, renal function and liver
             function

          -  Acute effects of any prior therapy resolved to baseline severity or to CTCAE Grade ≤1
             except for adverse events (AEs) that in the investigator' judgment do not constitute a
             safety risk for the participant.

          -  Systemic anti-cancer therapy with alectinib or ceritinib discontinued within a minimum
             of 5 half-lives prior to first dose of lorlatinib on the study (unless clinically
             meaningful tumor flare per discretion of the investigator, in which discussion with
             the sponsor is warranted).

          -  Male participants are eligible to participate if they agree to use proper
             contraception during the intervention period and for at least 98 days after the last
             dose of study intervention

          -  Female participants are eligible to participate if they are not pregnant or
             breastfeeding, and agree to use proper contraception during the intervention period
             and for at least 35 days after the last dose of study intervention.

          -  Capable of giving signed informed consent and willingness and ability to comply with
             the study scheduled visits and other procedures.

        Exclusion criteria:

          -  Prior ALK TKI treatment or anti-cancer treatment other than first line alectinib or
             ceritinib.

          -  Spinal cord compression unless the participant has good pain control attained through
             therapy, and there is stabilization or recovery of neurological function for the 4
             weeks prior to randomization.

          -  Gastrointestinal abnormalities, including inability to take oral medication;
             requirement for intravenous alimentation; prior surgical procedures affecting
             absorption including total gastric resection or lap band; active inflammatory
             gastrointestinal disease, chronic diarrhea, symptomatic diverticular disease;
             treatment for active peptic ulcer disease in the past 6 months; malabsorption
             syndromes.

          -  Active and clinically significant bacterial, fungal, or viral infection including
             hepatitis B virus (HBV) or hepatitis C virus (HCV), known human immunodeficiency virus
             (HIV), or acquired immunodeficiency syndrome (AIDS) related illness.

          -  Clinically significant vascular (both arterial and venous) and non-vascular cardiac
             conditions, (active or within 3 months prior to enrollment)

          -  Participants presenting with abnormal Left Ventricular Ejection Fraction (LVEF) by
             echocardiogram or Multi-Gated Acquisition Scan according to institutional lower
             limits.

          -  Participants with predisposing characteristics for acute pancreatitis according to
             investigator judgment

          -  History or known presence of interstitial fibrosis, interstitial lung disease,
             pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative
             bronchiolitis, and pulmonary fibrosis.

          -  Other severe acute or chronic medical or psychiatric condition, including recent
             (within the past year) or active suicidal ideation or behavior, or laboratory
             abnormality that may increase the risk associated with study participation or
             investigational product administration or may interfere with the interpretation of
             study results and, in the judgment of the investigator, would make the participant
             inappropriate for entry into this study.

          -  Evidence of active malignancy (other than current NSCLC, non-melanoma skin cancer, in
             situ cervical cancer, papillary thyroid cancer, ductal carcinoma in situ (DCIS) of the
             breast or localized and presumed cured prostate cancer) within the last 3 years prior
             to randomization.

          -  Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study
             entry. Palliative radiation must have been completed at least 48 hours prior to study
             entry. Stereotactic or small field brain irradiation must have completed at least 2
             weeks prior to study entry. Whole brain radiation must have completed at least 4 weeks
             prior to study entry.

          -  Prior irradiation to >25% of the bone marrow.

          -  Concurrent use of any of the following food or drugs within 12 days prior to the first
             dose of lorlatinib: known strong CYP3A inducers, known strong CYP3A inhibitors, known
             CYP3A substrates with narrow therapeutic index, known permeability glycoprotein (P-gp)
             substrates with a narrow therapeutic index

          -  Major surgery within 4 weeks prior to enrollment.

          -  Known prior or suspected severe hypersensitivity to study interventions or any
             component in their formulations.

          -  Investigator site staff members directly involved in the conduct of the study and
             their family members, site staff members otherwise supervised by the investigator, or
             Pfizer employees, including their family members, directly involved in the conduct of
             the study.