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 recurrentdisease and patient must have received at least one dose of the current regimen.Patients must have previously received or currently be receiving a platinum-basedhemotherapy regimen or anti-PD-1/PD-L1 therapy, alone or in combination (e.g.volumab or Pembrolizumab). Patients on first-line treatment are eligible uponving Cycle 1, Day 1 infusion. Note: Patients will not receive their sub-studygnment until they progress and the LUNGMAP Notice of Progression is submitted.. Patients must have adequate tumor tissue available, defined as ≥ 20% tumor cells and ≥.2 mm3 tumor volume.The local interpreting pathologist must review the specimen.The pathologist must sign the LUNGMAP Local Pathology Review Form confirmingue adequacy prior to Step 1 registration.Patients must agree to have this tissue submitted to Foundation Medicine for commonbroad platform CLIA biomarker profiling, PD-L1, and c-MET IHC (see Section 15.2). Ifhival tumor material is exhausted, then a new fresh tumor biopsy that isd and paraffin-embedded (FFPE) must be obtained. Patients who need theh biopsy must also submit whole peripheral blood for ctDNA testing. A tumor blockFFPE slides 4-5 microns thick must be submitted. Bone biopsies are not allowed. IfFFPE slides are to be submitted, at least 12 unstained slides plus an H&E stainedde, or 13 unstained slides must be submitted. However, it is strongly recommendedhat 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 useub-study Translational Medicine (TM) studies at the time of consent the patient isd 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 havegressed following all standard of care targeted therapy. EGFR/ALK/ROS/BRAF testingquired prior to Step 1 registration, as it is included in the Foundation Oneg for screening/pre-screening.6. Patients must have Zubrod performance status 0-1 (see Section 10.2) documented within28 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 asdescribed in Section 15.0.9. Patients must be willing to provide prior smoking history as required on the LUNGMAPudy Form.10. As a part of the OPEN registration process (see Section 13.4 for OPEN accessuctions) the treating institution's identity is provided in order to ensure thathe current (within 365 days) date of institutional review board approval for thisudy has been entered in the system.11. Patients must be informed of the investigational nature of this study and must signd give written informed consent in accordance with institutional and federalguidelines.12. U.S. patients who can complete the survey and the interview by telephone or email inglish must be offered participation in the S1400GEN Survey Ancillary Study if localution's policies allow participants to receive the Amazon gift card (see15.7 and 18.5). Patients at institutions that cannot offer the survey musthe main study.