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

5.1 Registration

Step 0:

   1. Patients who need the fresh biopsy must also submit whole blood for ctDNA testing (see
   Section 15.3). These patients must be registered to Step 0 to obtain a patient ID
   number for the submission.

   Patients registered to Step 0 are not registered to the LUNGMAP protocol. To
   participate in LUNGMAP, patients must be registered to Step 1 after evaluation of
   patient eligibility, including tumor tissue adequacy, per protocol Section 5.1, Step
   1.

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

   Step 1:

   2. Patients must have pathologically proven non-small cell lung cancer (all histologic
   types) confirmed by tumor biopsy and/or fine-needle aspiration. Disease must be Stage
   IV as defined in Section 4.0, or recurrent. The primary diagnosis of non-small cell
   lung cancer should be established using the current WHO/IASLC-classification of
   Thoracic Malignancies. All histologies, including mixed, are allowed.

   3. Patients 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:

      1. Screening at progression on prior treatment:

      To be eligible for screening at progression, patients must have received at least
      one line of systemic therapy for any stage of disease (Stages I-IV) and must have
      progressed 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 recurrent
         disease), disease progression on platinum-based chemotherapy must have
         occurred within one year from the last date that patient 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 one year from the
         date or initiation of such therapy.

         - For patients whose prior therapy was for Stage IV or recurrent disease, the
         patient must have received at least one line of a platinum-based
         chemotherapy 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.