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 determine eligibility for participation in the biomarker-driven and non-match sub-studies included within the Lung-MAP umbrella protocol, by testing participant specimens or collecting results of prior testing by protocol-approved biomarker assays.

SECONDARY SCREENING SUCCESS RATE OBJECTIVE:
I. To evaluate the percentage of participants assigned to a sub-study that register to a sub-study.

SECONDARY TRANSLATIONAL MEDICINE OBJECTIVE:
I. To summarize the prevalence of biomarkers either reported through previously completed tests or determined via on-study biomarker testing.

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 with pembrolizumab 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.

S1800E: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive dexamethasone PO BID on days 0-2, ramucirumab IV over 30-60 minutes on day 1 and docetaxel IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, and CT or MRI throughout the study.

ARM II: Patients receive dexamethasone PO BID on days 0-2, ramucirumab IV over 30-60 minutes on day 1, docetaxel IV over 60 minutes on day 1, and cemiplimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, and CT or MRI throughout the study.

S1900G: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive capmatinib PO BID, osimertinib PO QD, and ramucirumab IV over 30-60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI and collection of blood samples throughout the trial.

ARM B: Patients receive capmatinib PO BID and osimertinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI and collection of blood samples throughout the trial.

S1900J: Patients receive amivantamab SC on days 1, 8, 15, and 22 of cycle 1 and then on days 1 and 15 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and collection of blood samples throughout the trial.

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