Inclusion Criteria:

          1. Provision to sign and date the consent form.

          2. Stated willingness to comply with all study procedures and be available for the
             duration of the study.

          3. Male or female subject ≥ 18 years old

          4. ECOG performance status 0-2

          5. Stage IV NSCLC with progression of disease in the CNS on osimertinib 80 mg daily for
             patients with EGFR activating mutations (EGFR exon 19 deletions or EGFR L858R exon 21
             point mutations) -OR- Stage IV NSCLC with progression of disease in the CNS on
             lorlatinib 100 mg daily for patients with ALK fusions

          6. Evaluable CNS disease is required, measurable CNS disease is not required

          7. Patients who are on corticosteroids must be on stable or decreasing doses of
             corticosteroids for at least 14 days.

          8. Adequate hematologic function defined as:

               -  ANC ≥ 1.5 x 10^9/L

               -  Hemoglobin ≥ 9 g/dL

               -  Platelets ≥ 150 x 10^9/L

          9. Adequate hepatic function defined as:

               -  Total bilirubin ≤1.5 x upper limit of normal (ULN). For subjects with Gilbert's
                  Disease, Total bilirubin ≤3 x ULN

               -  ALT and AST ≤3 x ULN. For subjects with documented liver metastases, ALT and AST
                  ≤5×ULN

         10. Adequate renal function defined as:

               -  Estimated glomerular filtration rate (eGFR) ≥ 40 mL/minute as determined using
                  the Cockcroft-Gault formula

         11. Patients must be capable of taking oral medication and have no known gastrointestinal
             malabsorption disorder.

         12. Patients must not be planning to receive any concurrent chemotherapy, immunotherapy,
             biologic or hormonal therapy for cancer treatment while receiving treatment on this
             study. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for
             diabetes and hormone replacement therapy) is acceptable.

         13. Brain MRI with contrast is required to have demonstrated progressive CNS disease or an
             LP with cytology is required to have demonstrated progressive leptomeningeal disease
             on osimertinib or lorlatinib within 21 days of starting study drugs. CT of brain with
             contrast can be used to demonstrate progressive disease if patients have a documented
             anaphylaxis to gadolinium contrast and/or other contraindication to MRI (e.g., severe
             claustrophobia that cannot be managed with anxiolytics).

         14. Patients must not be pregnant. Women/men of reproductive potential must have agreed to
             use an effective contraceptive method (see section 6.6 for list of effective methods).
             Women must use an effective contraceptive method during the study and for 6 months
             following the last dose. Men having sex with women of reproductive potential are
             required to use effective contraception during the study and for 6 months following
             the last dose. A woman is considered to be of "reproductive potential" if she has had
             menses at any time in the preceding 12 consecutive months. In addition to routine
             contraceptive methods, "effective contraception" (see section 6.6 for list of
             effective contraceptive methods) also includes heterosexual celibacy and surgery
             intended to prevent pregnancy (or with a sideeffect of pregnancy prevention) defined
             as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at
             any point a previously celibate patient chooses to become heterosexually active during
             the time period for use of contraceptive measures outlined in the protocol, he/she is
             responsible for beginning contraceptive measures. Women of reproductive potential are
             not to be nursing during the study and for six months following the last dose of all
             study drugs.

         15. Women on the lorlatinib arm who are of reproductive potential agree to use a
             non-hormonal method of contraception during the study and for the time periods
             outlined above.

        Exclusion Criteria:

          1. Patients with compound mutations in EGFR will be excluded from this study. Compound
             mutations are defined as 2 or more mutations in the EGFR tyrosine kinase domain with
             the following exceptions:

               1. C797S and EGFR exon 19 deletion or EGFR exon 21 point mutation and

               2. T790M mutation and EGFR exon 19 deletion or EGFR exon 21 point mutation.

          2. Prior therapy with temozolomide.

          3. Patients must not receive surgery or radiation as local therapies for the progressing
             CNS disease for which they are being enrolled on this trial. Ventriculoperitoneal
             shunt placement will be allowed for leptomeningeal disease with symptomatic
             hydrocephalis. Radiation or surgery for progressing extra-CNS disease is allowed.

          4. Patients with a history of an allergic/hypersensitivity reaction to any component of
             temozolomide, dacarbazine, osimertinib (for temozolomide plus osimertinib arm) or
             lorlatinib (for temozolomide plus lorlatinib arm).

          5. Grade III/IV cardiac disease as defined by the New York Heart Association Criteria
             (i.e., patients with cardiac disease resulting in marked limitation of physical
             activity or resulting in inability to carry on any physical activity without
             discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or
             serious uncontrolled cardiac arrhythmia.

          6. Patients with a history of baseline QTcF interval greater than 470 msec on
             electrocardiogram for the osimertinib plus temozolomide arm only.

          7. Unstable or clinically significant concurrent medical condition, psychiatric illness
             or social situation that would, in the opinion of the investigator, jeopardize the
             safety of a subject and/or their compliance with the protocol.

          8. Clinically significant acute infection requiring systemic antibacterial, antifungal,
             or antiviral therapy. Suppressive therapy for chronic infections allowed, for example:

             Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be
             allowed. Subjects with viral hepatitis with controlled viral load would be allowed
             while on suppressive antiviral therapy.

          9. Treated with any investigational drug or chemotherapy within 3 weeks or ≤ 5 half-lives
             of first dose of study treatment.

         10. No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
             Stage I or II cancer from which the patient is currently in complete remission, or any
             other cancer from which the patient has been disease free for five years.

         11. Patient is not taking any prohibited medications listed in section 6.4. (Strong CYP3A
             inducers should be stopped greater than 3 half-lives prior to starting study drugs for
             patients on either study drug combination. Moderate inducers of CYP3A should be
             stopped greater than 3 half-lives prior to starting study drugs for patients receiving
             lorlatinib plus temozolomide. Strong CYP3A inhibitors should be stopped greater than 3
             half-lives prior to starting study drugs for patients receiving lorlatinib plus
             temozolomide.)