Summary

This expansion of the screening and multi-sub-study Lung-MAP trial is motivated by the changing landscape due to progress in the development of immunotherapies. The Lung-MAP trial was originally opened in June of 2014 for second-line treatment of participants with stage IV squamous lung cancer or squamous lung cancer that has come back (recurrent). The trial was amended to allow all participants with previously-treated stage IV or recurrent squamous lung cancer in 2015. The study is now expanding to allow participants with all types of previously-treated stage IV or recurrent non-small cell lung cancer. The type of cancer trait (biomarker) will determine to which sub-study, within this protocol, a participant will be assigned in order to compare new targeted cancer therapy designed to block the growth and spread of cancer, 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 participants not eligible for any of the biomarker-driven sub-studies.

Objectives

PRIMARY OBJECTIVE:
I. 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 SCREENING SUCCESS RATE OBJECTIVE:
I. To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study.

SECONDARY TRANSLATIONAL MEDICINE OBJECTIVE:
I. To establish a tissue/blood repository.

ANCILLARY STUDY S1400GEN OBJECTIVES (CLOSED TO ACCRUAL 06/30/2019):
PRIMARY OBJECTIVE:
I. To evaluate patient attitudes and preferences about return of somatic mutation findings suggestive of a germline mutation in the Lung-MAP Screening Study.

SECONDARY OBJECTIVES:
I. 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.
II. To evaluate Lung-MAP patients’ and study physicians’ knowledge of cancer genomics.
III. To evaluate Lung-MAP patients’ and study physicians’ knowledge of the design of the Lung-MAP Screening Study.
IV. To explore whether physician and patient knowledge of cancer genomics and attitudes and preferences about return of genomic profiling findings are correlated.

OUTLINE:
Participants undergo collection of tumor tissue samples or submit previous genomic profile testing results. Participants are then assigned to a biomarker-driven or non-match sub-study based on biomarker results of tumor tissue samples.

S1800A (NON-MATCH SUB-STUDY): Patients are randomized to 1 of 2 arms.

ARM A: Patients may receive docetaxel intravenously (IV) over 30-60 minutes on day 1, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, pemetrexed IV over 10 minutes on day 1 (non-squamous non-small cell lung cancer [NSCLC] patients only), or ramucirumab IV over 30-60 minutes combined with docetaxel IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) scans and collection of blood samples throughout the trial.

ARM B: Patients receive ramucirumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI scans and collection of blood samples throughout the trial.

S1800D: Patients are randomized to 1 of 2 arms.

ARM A: Patients may receive standard of care consisting of docetaxel IV over 30-60 minutes on day 1 of each cycle; gemcitabine IV over 30 minutes on days 1 and 8 of each cycle; pemetrexed IV over 10 minutes on day 1 of each cycle; or ramucirumab IV over 30-60 minutes and docetaxel IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and collection of blood samples throughout trial.

ARM B: Patients receive pembrolizumab IV over 30 minutes and nogapendekin alfa subcutaneously (SC) on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients then receive nogapendekin alfa SC on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and collection of blood samples throughout trial.

S1900A: Patients with genomic loss of heterozygosity (LOH) high and/or deleterious BRCA1/2 mutation receive rucaparib orally (PO) twice daily (BID) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

S1900B (CLOSED TO ACCRUAL 5/01/2021) : Patients with RET fusion receive selpercatinib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and undergo blood sample collection throughout the trial.

S1900C (CLOSED TO ACCRUAL 12/18/2020): Patients with STK11 somatic mutation or STK11 bi-allelic loss receive talazoparib PO daily and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and blood sample collection throughout the trial.

S1900E: Patients with KRAS G12C mutation receive sotorasib PO once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

S1900F: Patients with RET fusion are randomized to 1 of 2 arms.

ARM A: Patients receive carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also selpercatinib PO BID in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans during screening and on study, and collection of blood samples on study.

ARM B: Patients receive carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans during screening and on study, and collection of blood samples on study.

S1900K: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive ramucirumab IV over 30-60 minutes on day 1 of each cycle and tepotinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo lymphoscintigraphy scan at screening prior to treatment, at the first occurrence of peripheral edema (defined as the development of grade = 1 Common Terminology Criteria for Adverse Events [CTCAE] Edema Limbs affecting either the arms, hands, or legs), and if peripheral edema increases in attribution. Patients also undergo CT scan and/or MRI throughout the trial. Patients also undergo blood sample collection while on study.

ARM B: Patients receive tepotinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo lymphoscintigraphy scan at screening prior to treatment, at the first occurrence of peripheral edema (defined as the development of grade = 1 CTCAE Edema Limbs affecting either the arms, hands, or legs), and if peripheral edema increases in attribution. Patients also undergo CT scan and/or MRI throughout the trial. Patients also undergo blood sample collection while on study.

ANCILLARY STUDY S1400GEN (OPTIONAL) (CLOSED TO ACCRUAL AS OF 6/30/2019):
Patients and physicians of patients enrolled to Lung-MAP complete a telephone-based survey over 25-30 minutes (patients) or a web-based survey over 10-15 minutes (physicians) that focuses on knowledge, attitudes, and preferences about genetic findings.

After completion of study intervention, participants are followed up every 6 months for up to 3 years.

Eligibility

1. Patients must have pathologically or cytologically proven non-small cell lung cancer (NSCLC; all histologic types). Patients must have stage IV disease, or recurrent/progressive disease without a curative treatment option available. Mixed NSCLC histologies, are acceptable, but any known component of small cell lung cancer is not allowed
2. Patients must either have progression on prior systemic treatment or have received at least one dose of systemic treatment as defined below. 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 screening patients with known RET fusion positive NSCLC see S1900F *** For patients whose prior therapy was for Stage IV or recurrent disease, the patient must have received at least one line of a standard of care therapy for Stage IV or recurrent disease (See current NCCN guidelines) *** For patients who received adjuvant chemotherapy, progression must have occurred within one year from last date that patient received that therapy. For patients receiving adjuvant osimertinib, disease progression must have occurred on osimertinib. For patients treated with anti-PD-1 or anti-PD-L1 therapy for Stage I-III disease, disease progression on consolidation anti-PD-1 or anti-PD-L1 therapy must have occurred within one year form the date of initiation of such therapy. If disease progression was greater than one year after prior therapy, patients much receive subsequent systemic therapy to be eligible. *** For patients whose prior systemic therapy was for Stage I-III disease only (i.e., patient has not received any systemic treatment for Stage IV or recurrent/progressive 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 anti-PD-1 or anti-PD-L1 therapy for Stage I-III disease, disease progression on consolidation anti-PD-1 or anti-PD-L1 therapy must have occurred within one year from the date of initiation of such therapy. If disease progression was greater than one year after prior therapy, patients must receive subsequent systemic therapy to be eligible. * OR ** Pre-Screening prior to progression on current treatment: *** To be eligible for pre-screening, patients must have received at least one dose of a systemic regimen for Stage IV or recurrent/progressive disease and must be prior to progression on this regimen. *** Patients must have received or currently be receiving a first-line standard of care therapy. *** It is strongly recommended that patients receiving osimertinib do not pre-screen due to the S1900G eligibility **** Note: Patients will not receive their sub-study assignment until they progress and the LUNGMAP Notice of Progression is submitted. * Patients must meet one of the following criteria: ** Patient has adequate tissue available to submit for on-study biomarker profiling *** For patients with known EGFR mutation positive NSCLC that are screening for entry into S1900G, the tissue specimen must have been obtained after radiographic or clinical progression on osimertinib ** Patient has prior commercial FoundationOne CDx tissue-based (not liquid) tumor test results *** Note: For patients with known EGFR mutation positive, MET amplification positive NSCLC that are screening for entry into S1900G, the tissue specimen must have been obtained after radiographic or clinical progression on osimertinib ** Patient has documentation of prior known EGFR mutation positive, MET amplification positive NSCLC ** Patient has documentation of prior known MET exon 14 skipping positive NSCLC * Submitting tissue for on-study biomarker profiling: ** Patients must have adequate tumor tissue available, defined as >= 20% tumor cells and >= 0.2 mm^3 tumor volume. Specimens from bone biopsy are not allowed unless the specimen is entirely soft tissue or has not been decalcified. All other sites of tumor are acceptable, given the specimen meets all requirements for tissue adequacy. A formalin-fixed and paraffin-embedded (FFPE) tumor block or unstained FFPE slides 4-5 microns thick must be submitted. If slides are to be submitted, at least 12 unstained slides plus an H&E-stained slide, or 13 unstained slides must be submitted. However, if slides are to be submitted, it is strongly recommended that 20 unstained slides be submitted. Patients must agree to have this tissue submitted to Foundation Medicine for common broad platform CLIA biomarker profiling . If archival tumor material is exhausted, then a new tumor biopsy must be obtained. Patients must agree to have any leftover tissue (tissue that remains after biomarker testing) retained for the use of correlative studies outlined in the sub-study consents. * OR ** Submitting commercial FoundationOne CDx results for reanalysis: *** Patients must have a FoundationOne CDx report available with the following information: **** Results done on solid tumor tissue (liquid test not allowed) **** Original report date on or after September 1,2019 **** FMI Test Order # (e.g., ORD-1234567-01) Patients must consent to have their commercial FoundationOne CDx test results disclosed to SWOG Cancer Research Network.
3. Patients must meet one of the following criteria: * Patient has adequate tissue available to submit for on-study biomarker profiling ** Note: For patients with known EGFR-mutant NSCLC that are screening for entry into S1900G, the tissue specimen must have been obtained after radiographic or clinical progression on osimertinib. * Patient has prior commercial FoundationOne CDx tissue-based (not liquid) tumor test results ** Note: For patients with known EGFR-mutant, MET amplified NSCLC that are screening for entry into S1900G, the tissue specimen must have been obtained after radiographic or clinical progression on osimertinib. * Patient has documentation of prior known EGFR-mutant, MET amplified NSCLC. * Submitting tissue for on-study biomarker profiling: ** Patients must have adequate tumor tissue available, defined as >= 20% tumor cells and >= 0.2 mm^3 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 registration. ** Specimens from bone biopsy are not allowed unless the specimen is entirely soft tissue or has not been decalcified. All other sites of tumor are acceptable, given the specimen meets all requirements for tissue adequacy. ** A formalin-fixed and paraffin-embedded (FFPE) tumor block or unstained FFPE slides 4-5 microns thick must be submitted. If slides are to be submitted, at least 12 unstained slides plus a hematoxylin and eosin (H&E)-stained slide, or 13 unstained slides must be submitted. However, if slides are to be submitted, it is strongly recommended that 20 unstained slides be submitted. ** Patients must agree to have this tissue submitted to Foundation Medicine for common broad platform Clinical Laboratory Improvement Act (CLIA) biomarker profiling ** If archival tumor material is exhausted, then a new tumor biopsy must be obtained. ** Patients must agree to have any leftover tissue (tissue that remains after biomarker testing) retained for the use of correlative studies outlined in the sub-study consents. * OR * Submitting commercial FoundationOne CDx results for reanalysis: ** Patients must have a FoundationOne CDx report available with the following information: *** Results done on solid tumor tissue (liquid test not allowed) *** Original report date on or after September 1,2019 *** FMI Test Order # (e.g., ORD-1234567-01) *** Patients must consent to have their commercial FoundationOne CDx test results disclosed to SWOG Cancer Research Network
4. Patients’ most recent Zubrod performance status must be 0-1 and be documented within 28 days prior to registration
5. Patients must be >= 18 years of age
6. Patients must also be offered participation in banking for future use of specimens
7. Patients must be willing to provide prior smoking history as required on the LUNGMAP On-study Form
8. As a part of the OPEN registration process, 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
9. 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

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