Study of Lorlatinib In People With ALK-positive Non-small Cell Lung Cancer

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.
• 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,