Lorlatinib in Patients With ALK-Positive NSCLC With Brain or Leptomeningeal Metastases

Inclusion criteria

• ✓. Age ≥18 years, regardless of sex.
• ✓. Histologically or cytologically confirmed ALK-positive NSCLC.
• ✓. ALK rearrangement positive confirmed by FISH, RT-PCR, IHC Ventana D5F3, or NGS. Patients with other actionable genomic alterations in addition to ALK must be reviewed by the study expert panel to determine eligibility.
• ✓. Patients who have not received prior systemic treatment for advanced NSCLC, or who have experienced disease progression on or intolerance to at least one prior systemic treatment regimen, including an ALK inhibitor, are eligible for enrollment. If the treatment immediately prior to study drug administration was an ALK inhibitor, the washout period may be determined after discussion by the study expert panel.
• ✓. Toxicities related to prior systemic treatment must have recovered to ≤ Grade 1 (CTCAE version 5.0) or to baseline levels, except for adverse events that, in the investigator's judgment, do not pose a safety risk to the subject.
• ✓. At least one CNS lesion meeting one of the following criteria must be present: 1.leptomeningeal metastasis suggested by imaging and/or cerebrospinal fluid findings; cerebrospinal fluid confirmation is not required for imaging-suspected leptomeningeal metastasis; or 2.brain parenchymal metastasis confirmed by magnetic resonance imaging (MRI), with ≥3 brain lesions, or 1-2 lesions that are not suitable for surgery or for which the patient refuses surgery. In patients without leptomeningeal metastasis, at least one measurable brain lesion with a diameter of ≥5 mm is required.
• ✓. Patients with or without symptoms related to brain and/or leptomeningeal metastases are eligible.
• ✓. Life expectancy must be at least 12 weeks.

Exclusion criteria