Lorlatinib Combinations in Lung Cancer

Inclusion Criteria: * Ability to understand and the willingness to sign a written informed consent document. * Age ≥ 18 years. * Histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (Stage IV, AJCC v7.0) that carries an ALK or ROS1 rearrangement (ROS1-positive patients will only be allowed in dose escalation) as determined using a local diagnostic test or a commercial test or by the Food and Drug Administration (FDA)-approved FISH test, using Vysis® ALK Break apart FISH Probe, or the Ventana® immunohistochemistry (IHC) test. * Disease progression or intolerance to at least one tyrosine kinase inhibitor * At least one measurable lesion as defined by RECIST version 1.1. Previously irradiated lesions are not measurable unless the lesion has demonstrated clear progression after radiation. * ECOG performance status ≤ 2 * Life expectancy of greater than 12 weeks * Patients must be willing to undergo serial biopsies and have disease accessible to pretreatment biopsy. A cell block from a pleural effusion or ascites may be substituted for a core biopsy. In select cases, patients may be allowed to enroll without a pre-treatment biopsy and/or continue treatment without an on-treatment biopsy after speaking with the Overall Principal Investigator if performing the biopsy is technically challenging, poses significant risk to the patient, or may result in significant discomfort. If a pre-treatment biopsy is not performed, archival tissue will be use…