A Study of Targeted Radiation Therapy in People With Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria:

* Be greater than 18 years of age on day of signing informed consent.
* Have a histologically confirmed diagnosis of stage IV NSCLC (includes patients who have progressed on durvalumab for Stage III NSCLC) without known mutations in (EGFR) or BRAF or rearrangements in ALK (anaplastic lymphoma kinase) or ROS-1.

  o Patients with recurrent metastatic NSCLC following prior durvalumab for stage III disease are eligible provided this is their first immunotherapy course for metastatic disease (i.e., the planned anti-PD-(L)1-based regimen represents first-line systemic therapy in the metastatic setting).
* Newly diagnosed metastatic non-small cell lung cancer (NSCLC), including both de novo and secondary metastatic disease, with one or more liver metastases
* Plan to initiate standard of care anti-PD-(L)1 based immunotherapy +/- platinum based chemotherapy for at least 3 cycles

  o Regimens combining anti-CTLA-4 immunotherapy with anti-PD-1 (e.g., ipilimumab plus nivolumab) or anti-PD-L1 (e.g., tremelimumab plus durvalumab) immunotherapy are allowed.
* Have a performance status of 0-2 on the ECOG Performance Scale.
* Liver function tests:

  * Total Bilirubin ≤ 1.5 x ULN
  * AST/ ALT ≤ 5 x ULN
* Eligible for L- SABR to all liver metastases as determined by the treating radiation oncologist
* Patients with known HIV are eligible provided they are under treatment with effective anti-retroviral therapy with CD4 count \>200 cells/microliter within 28 days prior to registration

Exclusion Criteria:

* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen should be included.
* Patients with prior external beam radiation therapy to the liver.
* Patients with known active Hepatitis B or Hepatitis C.
* Patients with immunosuppression including pharmacological immunosuppression with chronic steroids or immune modulators like cyclosporin or methotrexate and patients with active autoimmune disease.
* Patients who are pregnant or breastfeeding
* Men or women not using effective contraception.