Radical-Dose Image Guided Radiation Therapy in Treating Patients With Metastatic Non-small Cell Lung Cancer Undergoing Immunotherapy

PRIMARY OBJECTIVES:

I. Determine if progression-free survival at 24 weeks with this treatment combination is
improved compared to historical controls who received immunotherapy without radiation
therapy.

SECONDARY OBJECTIVES:

I. Assess acute (0-6 months) and late (> 6 months) grade 3-5 toxicity. II. Assess overall
survival. III. Correlate circulating tumor deoxyribonucleic acid (DNA) (ratio of
post-radiation therapy [RT] to pre-RT level) with radiographic response.

IV. Correlate immune markers in peripheral blood with radiographic response.

TERTIARY OBJECTIVES:

I. Analyze progression-free survival with immune-related response criteria. II. Measure time
to discontinuation of study immunotherapy agent. III. Assess patterns of progression.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients undergo radical-dose image guided radiation therapy daily for up to 10 days
(within 2 weeks) while undergoing standard of care immunotherapy.

Arm II: Patients who decline to undergo radiation therapy receive standard of care
immunotherapy.

After completion of study treatment, patients are followed up at 30 days and every 6 months
thereafter.

Inclusion Criteria:

- Has metastatic non-small cell lung cancer (NSCLC)

- Has been receiving anti-PD-1 or anti-PD-L1 immunotherapy for at least four weeks

- Has had restaging imaging after initiation of immunotherapy, at least 4 weeks after
pre-immunotherapy baseline imaging; computed tomography (CT) or positron emission
tomography (PET)/CT of at least chest/upper abdomen must be performed within 4 weeks
prior to registration; for patients with history of brain metastases, brain magnetic
resonance imaging (MRI) or CT is required within 4 weeks of registration; for other
patients brain MRI or CT is required within 12 weeks of registration

- Is expected by the treating medical oncologist to continue on immunotherapy for at
least three more months; imaging must show response, stable disease, or modest
progression as determined by the treating medical oncologist; if there is modest
progression, the patient must be clinically stable in terms of performance status and
overall disease-related symptoms

- Has at least one extracranial tumor safely treatable with radical-dose radiation
therapy

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Has the ability to understand and the willingness to sign a written informed consent
document

Exclusion Criteria:

- Untreated brain metastases, if not planned to be treated in this course of radiation
therapy

- Pregnancy or women of childbearing potential not willing/able to use contraception
during protocol treatment