This screening and multi-sub-study randomized phase II/III trial will establish a method for
genomic screening of similar large cancer populations followed by assigning and accruing
simultaneously to a multi-sub-study hybrid Master Protocol (Lung-MAP). The type of cancer
trait (biomarker) will determine to which sub-study, within this protocol, a participant will
be assigned to compare new targeted cancer therapy, designed to block the growth and spread
of cancer, or combinations to standard of care therapy with the ultimate goal of being able
to approve new targeted therapies in this setting. In addition, the protocol includes
non-match sub-studies which will include all screened patients not eligible for any of the
biomarker-driven sub-studies.
Primary Objective of the Master Protocol (LUNGMAP)
The primary objective of this screening study is to test patient specimens to determine
eligibility for participation in the biomarker-driven and non-matched sub-studies included
within the Lung-MAP umbrella protocol.
Secondary Objectives
1. Screening Success Rate Objective
To evaluate the screen success rate defined as the percentage of screened patients that
register for a therapeutic sub-study. Screen success rates will be evaluated for the
total screened population and by the subset of patients screened following progression
on previous therapy or pre-screened on current therapy.
2. Translational Medicine Objectives
1. To evaluate circulating tumor DNA (ctDNA) and compare to the FMI Foundation tissue
molecular profiling results in patients who submit a new biopsy for screening.
2. To establish a tissue/blood repository.
Ancillary Study S1400GEN Objectives
The Lung-MAP Screening Study includes an ancillary study evaluating patient and physician
attitudes regarding the return of somatic mutation findings suggestive of a germline
mutation. Participation in this study is optional.
1. Primary Objective
To evaluate patient attitudes and preferences about return of somatic mutation findings
suggestive of a germline mutation in the Lung-MAP Screening Study.
2. Secondary Objectives
1. To evaluate Lung-MAP study physician attitudes and preferences about return of
somatic mutation findings suggestive of a germline mutation in the Lung-MAP
Screening Study.
2. To evaluate Lung-MAP patients' and study physicians' knowledge of cancer genomics.
3. To evaluate Lung-MAP patients' and study physicians' knowledge of the design of the
Lung-MAP Screening Study.
4. To explore whether physician and patient knowledge of cancer genomics and attitudes
and preferences about return of genomic profiling findings are correlated.
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.
