Hepatic Impairment Study for Lorlatinib in Cancer Patients

Inclusion Criteria

• Histologically or cytologically confirmed solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative or palliative measures do not exist, or are no longer effective;
• Biliary obstruction with a biliary drain or stent;
• Neurologically stable gliomas and brain metastases;
• ECOG performance status of 0, 1, or 2;
• adequate bone marrow function;
• adequate pancreatic function;
• adequate renal function;
• female patients with negative pregnancy test

Exclusion Criteria

• untreated esophageal varices; uncontrolled ascites;
• episodes of hepatic encephalopathy within the last 4 weeks;
• spinal cord compression; major surgery within 4 weeks prior to enrollment;
• radiation therapy within 2 weeks prior to enrollment;
• last anti-cancer treatment within 2 weeks prior to screening;
• previous high-dose chemotherapy requiring stem cell rescue;
• prior to irradiation to >25% of the bone marrow;
• gastrointestinal abnormalities;
• known prior or suspected hypersensitivity to lorlatinib or lorlatinib tablet;
• clinically significant bacterial, fungal or viral infections for non-liver cancer patients;
• clinically significant cardiovascular disease;
• uncontrolled hypertension; acute pancreatitis with predisposing characteristics;
• history of grade 3 or 4 interstitial fibrosis or interstitial lung disease;
• active hemoelysis or evidence of biliary sepsis;
• prior major gastrointestinal surgery;
• concurrent use of known strong CYP3A inhibitors, inducers and P-gp substrates with a narrow therapeutic index;
• concurrent use of CYP3A substrates with narrow therapeutic indices;
• prior treatment with lorlatinib; active bleeding disorder