Nivolumab with or without Ipilimumab as Second-Line Therapy in Treating Patients with Recurrent Stage IV Squamous Cell Lung Cancer and No Matching Biomarkers (A Lung-MAP Treatment Trial)

Inclusion Criteria

• Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)
• Patients must have been assigned to S1400I
• Patients must also be offered participation in banking for future use of specimens
• Patients must have a lipase, amylase, TSH with reflex free T3/T4 performed within 7 days prior to sub-study registration; (Note: For the Canadian sites, testing for lipase only is acceptable)
• Patients who can complete PRO forms in English are required to complete a pre-study S1400I Patient Reported Outcomes (PRO) Questionnaire and a pre-study S1400I EQ-5D Questionnaire within 14 days prior to registration; NOTE: Patients enrolled to S1400I prior to 9/1/2016 are not eligible for the PRO study
• Patients must have progressed (in the opinion of the treating investigator) following the most recent line of therapy
• Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI); the CT from a combined PET/CT may be used to document only non-measurable disease unless it is of diagnostic quality; measurable disease must be assessed within 28 days prior to sub-study registration; pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease; non-measurable disease must be assessed within 42 days prior to sub-study registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form; patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration
• Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study registration; patient must not have leptomeningeal disease, 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 prior to 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 have fully recovered from the effects of major surgery at least 14 days prior to sub-study registration
• Patients must have an absolute neutrophil count (ANC) >= 1,500/mcL (obtained within 28 days prior to sub-study registration)
• Platelet count >= 100,000 mcL (obtained within 28 days prior to sub-study registration)
• Hemoglobin >= 9 g/dL (obtained within 28 days prior to sub-study registration)
• Serum bilirubin =< institutional upper limit of normal (IULN) within 28 days prior to sub-study registration
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN within 28 days prior to sub-study registration (if both ALT and AST are done, both must be =< 2 IULN).
• For patients with liver metastases, bilirubin and either ALT or AST must be =< 5 x IULN (if both ALT and AST are done, both must be =< 5 x IULN
• Serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50 mL/min using the following Cockroft-Gault Formula
• Patients must have Zubrod performance status of 0-1 documented within 28 days prior to sub-study registration
• Prestudy history and physical exam must be obtained within 28 days 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 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 five years
• 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
• Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
• 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

Exclusion Criteria

• Patients must not have had prior treatment with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
• Patients must not have an active, known, or suspected autoimmune disease; patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Patients must not have any known allergy or reaction to any component of the nivolumab and ipilimumab formulations
• Patients must not have received systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to sub-study registration; inhaled or topical steroids, and adrenal replacement doses =< 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease
• Patients must not have a known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection; patients with a positive hepatitis C antibody with a negative viral load are allowed
• Patients must not have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Patients must not have interstitial lung disease that is symptomatic or disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity
• 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 with a history of congestive heart failure (CHF) or at risk because of underlying cardiovascular disease or exposure to cardiotoxic drug should have an electrocardiogram (EKG) and echocardiogram performed to evaluate cardiac function as clinically indicated * Patients with evidence of congestive heart failure (CHF), myocardial infarction (MI), cardiomyopathy, or myositis should have a cardiac evaluation including lab tests and cardiology consultations as clinically indicated including EKG, creatine phosphokinase (CPK), troponin, and echocardiogram
• Patients whose biomarker profiling results indicate the presence of an EGFR mutation or EML4/ALK fusion are not eligible. Due to existence of approved therapies the biomarker exclusion rules are as follows: * EGFR Gene: substitution (L858R, T790M, A289V, G719A, S768I, G719C, R108K, G598V, R222C, L62R, L861Q, P596L, V774M), indel (non-frame shifting insertions or deletions between amino acids 740 and 780, in exons 19 and 20, transcript NM_005228), fusion (none), amplification (none) * ALK Gene: substitution (none), indel (none), fusion (EML4-ALK, CLIP4-ALK, CLTC-ALK, KIF5B-ALK, NPM1-ALK, RANB2-ALK, STRN-ALK, TFG-ALK), amplification (none)
• 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 not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.; concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable
• Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures