Delayed or Upfront Brain RAdiotherapy in Treatment naïve Lung Cancer Patients With Asymptomatic or Minimally Symptomatic Brain Metastases and ALK rEarrangements

General Inclusion Criteria:

Subject must meet all of the following applicable inclusion criteria to participate in this study:

1. Written informed consent and HIPAA authorization for release of personal healthinformation prior to registration. NOTE: HIPAA authorization may be included in theinformed consent or obtained separately.

2. Age ≥ 18 years at the time of consent.

3. Fluent English skills with comprehensive/speaking skills equal to those of a nativeEnglish speaker as assessed by the site investigator.

4. ECOG Performance Status of ≤ 2 within 14 days prior to registration.

5. Histological or cytological confirmation of Stage IV (per AJCC 8th edition)non-small cell lung cancer (NSCLC).

6. At least one intracranial metastasis on MRI imaging.

7. Confirmation of positive ALK rearrangement per local standard of care testing.

8. All subjects must have brain metastases and be either asymptomatic or minimallysymptomatic per investigator discretion without plan for surgical interventionwithin 28 days of study start. Patients with neurological symptoms that arecontrolled with dose of corticosteroids or anti-epileptic medications are eligible.Patients with asymptomatic leptomeningeal disease may be eligible for trialproviding they meet all other eligibility criteria.

9. Subjects must be planning on therapy with alectinib. Alectinib may have been startedup to 6 weeks prior to registration.

10. Prior non-ALK directed therapy for metastatic disease is permitted. Patients whohave received prior neoadjuvant or adjuvant chemotherapy, radiotherapy,immunotherapy (PD-1 or PD-L1 monoclonal antibodies) or chemoradiotherapy withcurative intent for non-metastatic disease must have experienced a treatment-freeinterval of at least 3 months from registration since the last chemotherapy,radiotherapy, immunotherapy, or chemoradiotherapy cycle.

11. Documentation of consultation with a radiation oncologist confirming agreement todelay radiation therapy.

12. Demonstrate adequate organ function as defined in the protocol. All screening labsto be obtained within 14 days prior to registration.

13. Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. See protocol for definition of childbearingpotential.

14. Females of childbearing potential and males must be willing to abstain fromheterosexual intercourse or to use an effective method(s) of contraception asoutlined in the protocol.

15. HIV-infected patients on effective anti-retroviral therapy with undetectable viralload within 6 months of registration are eligible for this trial.

16. Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viralload must be undetectable on suppressive therapy, if indicated. Patients with ahistory of hepatitis C virus (HCV) infection must have been treated and cured. Forpatients with HCV infection who are currently on treatment, the HCV viral load mustbe undetectable to be eligible for this trial.

17. As determined by the enrolling physician or protocol designee, ability of thesubject to understand and comply with study procedures for the entire length of thestudy.

Exclusion Criteria:

Subjects meeting any of the criteria below may not participate in the study:

1. Active infection requiring systemic therapy.

2. Malabsorption syndrome or other condition that would interfere with enteralabsorption

3. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use whilethe mother is being treated on study).

4. Patients with a prior or concurrent malignancy whose natural history or treatmenthas the potential to interfere with the safety or efficacy assessment of theinvestigational regimen, per treating physician discretion, are not eligible forthis trial.

5. Treatment with any investigational drug within 28 days prior to registration.

6. Acute viral, autoimmune, alcoholic, or other types of acute hepatitis.