Neoadjuvant Immunotherapy in Treating Patients with Stage IB-IIIA Non-small Cell Lung Cancer That Can Be Removed by Surgery

Inclusion Criteria

• Histologically proven non-small-cell lung cancer (core biopsy required) * Squamous or non-squamous histology * Diagnostic core biopsy specimens must be reviewed by a faculty pathologist at Sidney Kimmel Comprehensive Cancer Center (SKCCC), McGill University Health Center (McGill), Swedish Cancer Institute (SCI), or Memorial Sloan Kettering Cancer Center (MSKCC) * Either a formalin fixed paraffin block that has been confirmed by a pathologist to contain tumor or a minimum of twenty 5-micron tissue sections (slides) of tumor biopsy sample must be available for biomarker evaluation (study pathologist must review for adequacy of sampling); this can be obtained from archived tissues if adequate, or from a new biopsy as needed
• Stage - NSCLC with primary resection option for potential cure, as assessed by a faculty surgeon at SKCCC, McGill, SCI, or MSKCC; this may include clinical stage IB (>= 4 cm), II and IIIA; subjects with N3 nodal involvement are not included
• For patients enrolled at Johns Hopkins only, a bronchoscopy will be required after consent (prior to initiation of treatment)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Leukocytes >= 2,000/mm^3
• Absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3
• Hemoglobin >= 9 g/dL
• Creatinine =< 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft‐Gault formula)
• Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 times the upper limit of normal
• Alkaline phosphatase =< 3 times the upper limit of normal
• Subjects must have adequate lung function to permit surgical resection determined by pre-enrollment pulmonary function tests to include diffusing capacity of the lungs for carbon monoxide (DLCO)
• The effects of nivolumab on the developing human fetus are unknown; paclitaxel and carboplatin are pregnancy category D; for this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for up to 23 weeks after the last dose of nivolumab and/or chemotherapy; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; sexually active fertile men must use effective barrier birth control if their partners are WOCBP for up to 31 weeks after the last dose of nivolumab; WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within two weeks of registration; women must not be breastfeeding
• Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form; voluntary signed and dated Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent form in accordance with regulatory and institutional guidelines must be obtained before the performance of any protocol related procedures that are not part of normal patient care
• Subjects must be competent to report adverse events (AEs), understand the drug dosing schedule and use of medications to control AEs

Exclusion Criteria

• Subjects are excluded if they have an active, known or suspected autoimmune disease; subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Subjects are excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab‐containing regimen
• Administration of chemotherapy or any other cancer therapy in the pre-operative period other than that indicated by treatment Arm C
• Subjects with active concurrent malignancies are excluded i.e. cancers other than NSCLC (except non-melanoma skin cancers, in situ bladder, gastric, breast, colon or cervical cancers/dysplasia)
• Subjects with brain metastasis are excluded from this study, and all patients should have brain imaging (either magnetic resonance imaging [MRI] brain or CT brain with contrast) prior to enrollment
• Subjects with a history of symptomatic interstitial lung disease
• Active systemic infection requiring therapy, positive tests for hepatitis B surface antigen or hepatitis C antibody
• Known positive history or positive test for human immunodeficiency virus or acquired immunodeficiency syndrome (AIDS)
• History of allergy to study drug components
• Women who are pregnant or nursing
• Men with female partners (WOCBP) that are not willing to use contraception
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-regulatory pathways)
• Underlying medical conditions that, in the investigator’s opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events
• Prisoners or subjects who are involuntarily incarcerated or compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness
• History of allergy or hypersensitivity to study drug components
• > grade 2 peripheral neuropathy (Arm C only)