This National Cancer Institute (NCI)-NRG ALK Protocol phase II trial studies how well a combination of different biomarker/ALK inhibitors work in treating patients with stage IV ALK positive non-squamous non-small cell lung cancer. Lorlatinib, ceritinib, alectinib, brigatinib, ensartinib, and crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pemetrexed, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether a combination of biomarker/ALK inhibitors or chemotherapy may work better in treating patients with ALK positive non-squamous non-small cell lung cancer.

NCT03737994

Conditions

1. Lung Non-S
2. Lung Non-Squamous Non-Small Cell Carcinoma
3. Stage IV Lung Cancer AJCC v8
4. Stage IVA Lung Cancer AJCC v8
5. Stage IVB Lung Cancer AJCC v8

Interventions

1. Drug: Alectinib
2. Drug: Brigatinib
3. Drug: Carboplatin
4. Drug: Ceritinib
5. Drug: Cisplatin
6. Drug: Crizotinib
7. Drug: Ensartinib
8. Drug: Lorlatinib
9. Drug: Pemetrexed

MeSH:Lung Neoplasms

HPO:Neoplasm of the lung

For each ALK inhibitor therapy, the primary analysis is to compare the response rate for the patients who have the relevant mutation (G1202/C1156Y /I1171/L1196/ V1180/F1174/compound mutation) to those patients who receive the same ALK inhibitor therapy who have no mutations using Fisher's exact test. --- C1156Y ---

Patients with a history of prior radiation pneumonitis are not excluded - PRIOR TO STEP 2 REGISTRATION: Active inflammatory gastrointestinal disease (such as Crohns, ulcerative colitis), chronic diarrhea, symptomatic diverticular disease, or any gastrointestinal disease that would affect the absorption of oral medications or increase the risk of toxicity - PRIOR TO STEP 2 REGISTRATION: Clinically significant cardiovascular abnormalities, as determined by the treating/registering physician, such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia, or myocardial infarction within 6 months - PRIOR TO STEP 2 REGISTRATION: Active and clinically significant bacterial, fungal, or viral infection - PRIOR TO STEP 2 REGISTRATION: Patients with active or chronic pancreatitis based on lipase elevation, symptoms, and radiographic findings - PRIOR TO STEP 2 REGISTRATION: Other concomitant serious illness or organ system dysfunction that in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug - PRIOR TO STEP 2 REGISTRATION: Patients must not plan to receive any other investigational agents during the course of therapy - PRIOR TO STEP 2 REGISTRATION: Patients with active malignancy other than ALK-positive non-squamous NSCLC within the last 2 years are excluded (note: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, papillary thyroid cancer treated with curative intent, adequately treated stage I 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 2 years are eligible) - PRIOR TO STEP 2 REGISTRATION: No chemotherapy and/or immunotherapy allowed after step 1 registration Lung Non-S Lung Non-Squamous Non-Small Cell Carcinoma Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 Lung Neoplasms PRIMARY OBJECTIVES: I. To assess whether ALK kinase domain mutations (G1202/C1156Y/I1171/L1196/ V1180/ F1174/compound mutation) associated with drug resistance are prognostic for objective response to subsequent ALK inhibitor therapy. --- C1156Y ---

Patients with a C1156Y mutation receive either lorlatinib PO QD, brigatinib PO QD, or alectinib PO twice daily (BID). --- C1156Y ---