Lung-MAP: A Master Screening Protocol for Previously-Treated Non-Small Cell Lung Cancer

1. Patients who need the fresh biopsy must also submit whole blood for ctDNA testing (see15.3). These patients must be registered to Step 0 to obtain a patient IDumber for the submission.
   Patients registered to Step 0 are not registered to the LUNGMAP protocol. ToLUNGMAP, patients must be registered to Step 1 after evaluation ofgibility, including tumor tissue adequacy, per protocol Section 5.1, Step1.
   Patients registered at Step 0 must use the same SWOG patient ID for registration at1.
   Step 1:
2. Patients must have pathologically proven non-small cell lung cancer (all histologicypes) confirmed by tumor biopsy and/or fine-needle aspiration. Disease must be StageV as defined in Section 4.0, or recurrent. The primary diagnosis of non-small cellung cancer should be established using the current WHO/IASLC-classification ofThoracic Malignancies. All histologies, including mixed, are allowed.
3. Patients must either be eligible to be screened at progression on prior treatment orbe pre-screened prior to progression on current treatment.
   These criteria are:
   1. Screening at progression on prior treatment:
      To be eligible for screening at progression, patients must have received at leastystemic therapy for any stage of disease (Stages I-IV) and must havegressed during or following their most recent line of therapy.
      • For patients whose prior systemic therapy was for Stage I-III disease only(i.e. patient has not received any treatment for Stage IV or recurrentdisease), disease progression on platinum-based chemotherapy must haveurred within one year from the last date that patient received thatherapy. For patients treated with consolidation anti-PD-1 or anti-PD-L1herapy for Stage III disease, disease progression on consolidationPD-1 or anti-PD-L1 therapy must have occurred within one year from thedate or initiation of such therapy.
      • For patients whose prior therapy was for Stage IV or recurrent disease, theust have received at least one line of a platinum-basedhemotherapy regimen or anti-PD-1/PD-L1 therapy, alone or in combination(e.g. Nivolumab or Pembrolizumab).
   2. Pre-Screening prior to progression on current treatment:

       To be eligible for pre-screening, current treatment must be for Stage IV or recurrent
       disease and patient must have received at least one dose of the current regimen.
       Patients must have previously received or currently be receiving a platinum-based
       chemotherapy regimen or anti-PD-1/PD-L1 therapy, alone or in combination (e.g.
       Nivolumab or Pembrolizumab). Patients on first-line treatment are eligible upon
       receiving Cycle 1, Day 1 infusion. Note: Patients will not receive their sub-study
       assignment until they progress and the LUNGMAP Notice of Progression is submitted.
     4. Patients must have adequate tumor tissue available, defined as ≥ 20% tumor cells and ≥
       0.2 mm3 tumor volume.
        - The local interpreting pathologist must review the specimen.
        - 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
       formalin-fixed and paraffin-embedded (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 4-5 microns thick must be submitted. Bone biopsies are not allowed. If
       FFPE slides are to be submitted, at least 12 unstained slides plus an H&E stained
       slide, or 13 unstained slides must be submitted. However, it is strongly recommended
       that 20 FFPE slides be submitted. Note: Previous next-generation DNA sequencing (NGS)
       will be repeated if done outside this study for sub-study assignment.
       Patients must agree to have any tissue that remains after testing retained for the use
       of sub-study Translational Medicine (TM) studies at the time of consent the patient is
       enrolled in.
     5. 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.
     6. Patients must have Zubrod performance status 0-1 (see Section 10.2) documented within
       28 days prior to Step 1 registration.
     7. Patients must be ≥ 18 years of age.
     8. Patients must also be offered participation in banking for future use of specimens as
       described in Section 15.0.
     9. Patients must be willing to provide prior smoking history as required on the LUNGMAP
       Onstudy Form.
     10. 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.
     11. 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.
     12. U.S. patients who can complete the survey and the interview by telephone or email in
       English must be offered participation in the S1400GEN Survey Ancillary Study if local
       institution's policies allow participants to receive the Amazon gift card (see
       Sections 15.7 and 18.5). Patients at institutions that cannot offer the survey must
       still participate in the main study.