SWOG LUNGMAP

A Master Protocol to Evaluate Biomarker-Driven Therapies and Immunotherapies in Previously-Treated Non-Small Cell Lung Cancer (Lung-MAP Screening Study)

Inclusion Criteria

• 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 or recurrent.  All histologies, including mixed, are allowed. 
• Patients must either be eligible to be screened at progression on prior treatment or to be pre-screened prior to progression on current treatment. Patients will either consent to the Screening consent or the Pre-Screening consent, not both. 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 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 lease one line of a platinum-based chemotherapy regimen or anti-PD-1/PD-L1 therapy, alone or in combination (e.g. Nivolumab or Pembrolizumab).
  • 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 must have adequate tumor tissue available, defined as ≥ 20% tumor cells and ≥ 0.2 mm³tumor volume. The local interpreting pathologist must review and sign off on the Local Pathology Review Form prior to screening/pre-screening 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.  If archival tumor is exhausted, then a new fresh tumor biopsy that is formalin fixed and paraffin embedded must be obtained.
• 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 progessed 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. 
• Patients must have a Zubrod performance status 0-1 documented within 28 days prior to Step 1 registration.
• Patients must be ≥ 18 years of age.
• Patients must also be offered participation in banking for future use of specimens.
• Patients must be willing to provide prior smoking history.

Sub-Study Registration

• For patients screened at progression on prior treatment, a sub-study assignment should be received within 16 days of tissue submission.
• For patients pre-screened prior to progression on current therapy, submission of the Notice of Progression Form is required to receive a sub-study assignment. The sub-study assignment should be received from the SWOG Statistical Center within 1 day of submission of the form. Patients must then register to the assigned sub-study in order to receive their treatment randomization assignment.
• Patient must meet the common eligibility criteria across all sub-studies listed in this section below as well as any additional criteria listed in the assigned sub-study protocol. 
  
  • Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to sub-study registration.  Patients must have recovered (< Grade 1) from any side effects of prior therapy.  Patients must not have received any radiation therapy within 14 days prior to sub-study registration).
  • Patients must have measurable disease documented by CT or MRI.  Measurable disease must be assessed within 28 days prior to sub-study registration.  Non-measurable disease must be assessed within 42 days prior to sub-study registration. 
  • Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to sub-study registration.  Patient must not have leptomeningeal diasease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment and prior to sub-study registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study registration. 
  • Patients must not have any Grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia.
  • Patients must not have documented evidence of acute hepatitis or have an active or uncontrolled infection.
  • Patients with a known history of HIV seropositivity:
    • Must have undetectable viral load using standard HIV assays in clinical practice
    • Must have CD4 count > 400/mcL
    • Must not required prophylaxis for any opportunistic infections (i.e., fungal, MAC, or PCP prophylaxis)
    • Must not be newly diagnosed within 12 months prior to sub-study registration
  • No other prior malignancy is allowed except for the following:  
    • adequately treated basal cell or squamous cell skin cancer
    • in situ cervical cancer
    • adequately treated Stage 1 or II cancer from which the patient is currently in complete remission
    • or any other cancer from which the patient has been disease free for five years

Treatment Plan

Patients will first have fresh or archived tissue submitted for biomarker testing. Within 16 days, results will be available and eligible patients will be randomized to the appropriate sub-study, depending on the specific marker identified. The target biomarker for each sub-study is noted in parentheses below. Treatment on all sub-studies continues until progression of disease, symptomatic deterioration, unacceptable toxicity, treatment delay > 28 days, or patient withdrawal for any reason. Upon progression, patients may be eligible for another sub-study, as determined by the SWOG Statistical Center.

Sub-study F (Non-Match sub-study) Anti-PD-1/PD-L1 Inhibitor Resistant 
MEDI4736 (Durvalumab) plus Tremelimumab for 4 cycles followed by MEDI4736 (Durvalumab) alone
Tremelimumab 75mg IV every 28 days for up to 4 doses
Durvalumab (MEDI4736) 1500mg IV every 28 days until disease progression 

Sub-study S1900A
Rucaparib 600mg PO twice daily (one cycle = 21 days) 

All investigational study drugs (Durvalumab, Rucaparib & Tremelimumab) will be provided free of charge for these studies.

The biomarker testing will also be provided free of charge. If patients require a biopsy for eligibility, the cost of the biopsy will be paid for by the study.