Patients who need the fresh biopsy must also submit whole blood for ctDNA testing. These patients must be registered to Step 0 to obtain a patient ID number for the submission.

To participate in LUNGMAP, patients must be registered to Step 1 after evaluation of patient eligibility, including tumor tissue adequacy

Patients registered at Step 0 must use the same SWOG patient ID for registration at Step 1.

Step 1:

Must have pathologically proven NSCLC. Disease must be Stage IV.

Must either be eligible to be screened at progression on prior treatment or to be pre-screened prior to progression on current treatment.

These criteria are:

Screening at progression on prior treatment:

To be eligible for screening at progression, patients must have received at least one line of systemic therapy and have progressed during or following their most recent line of therapy

For patients whose prior systemic therapy was for Stage I-III disease only, disease progression on Pt-based chemo must have occurred within 1 year from the last date received that therapy. For patients treated with consolidation anti-PD-1 or anti-PD-L1 therapy for Stage III disease, disease progression on consolidation anti-PD-1 or anti-PD-L1 therapy must have occurred within 1 year from the date or initiation.

Patients whose prior therapy was for Stage IV, the patient must have received at least one line of a Pt-based chemotherapy regimen or anti-PD-1/PD-L1 therapy

Pre-Screening prior to progression on current treatment:

current treatment for Stage IV or recurrent disease and must have at least one dose of the current regimen. must previously received or currently receiving a Pt-based chemo regimen or anti-PD-1/PD-L1 therapy. first-line treatment are eligible upon C1D1 1infusion

Patients must have adequate tumor tissue available, defined as greater 20% tumor cells and greater 0.2 mm3 volume.

The pathologist must sign the LUNGMAP Local Pathology Review Form confirming tissue adequacy prior to Step 1 registration.

Patients must agree to have this tissue submitted to Foundation Medicine for common broad platform CLIA biomarker profiling, PD-L1, and c-MET IHC (see Section 15.2). If archival tumor material is exhausted, then a new fresh tumor biopsy that is FFPE must be obtained. Patients who need the fresh biopsy must also submit whole peripheral blood for ctDNA testing. A tumor block or FFPE slides be submitted. Bone biopsies are not allowed.

Patients must agree to have any tissue that remains after testing retained for the use of sub-study TM studies at the time of consent the patient is enrolled in

Patients with known EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, ROS 1 gene rearrangement, or BRAF V600E mutation are not eligible unless they have progressed following all standard of care targeted therapy. EGFR/ALK/ROS/BRAF testing is not required prior to Step 1 registration, as it is included in the Foundation One testing for screening/pre-screening.

Have Zubrod performance status 0-1 documented within 28 days prior to Step 1

Be 18 years of age

Offered participation in banking for future use of specimens

Be willing to provide prior smoking history as required on the LUNGMAP Onstudy Form.

As a part of the OPEN registration process (see Section 13.4 for OPEN access instructions) the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.