Nivolumab + Platinum-based Chemotherapy + Certolizumab for the Treatment of Resectable Stages II-III Non-Small Cell Lung Cancers

Inclusion Criteria

• Untreated stage II-III (American Joint Committee on Cancer [AJCC] 8th edition) non-small cell lung cancers with operable and resectable disease determined by a thoracic surgeon
• Histologic confirmation of disease at Memorial Sloan Kettering Cancer Center (MSKCC)
• Age 18 years or older
• Karnofsky performance status >= 70
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
• Lymphocyte count >= 0.5 x 10^9/L (500/uL)
• Hemoglobin >= 9 g/dL
• Platelets >= 100 x 10^9/L
• Serum total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients with documented Gilbert’s Syndrome)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• Serum creatinine =< 1.5 x upper limit of normal or creatinine clearance >= 60ml/min for patients with creatinine levels above institutional normal
• Serum albumin >= 25 g/L (2.5 g/dL)
• For patients not receiving therapeutic anticoagulation: international normalized ratio (INR) or activated partial thromboplastin time (aPTT) =< 1.5 x ULN
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Negative purified protein derivative (PPD) test or interferon-gamma release assay (including but not limited to QuantiFERON-tuberculosis [TB] Gold)
• For women of child-bearing potential, negative pregnancy test within 14 days prior to starting treatment
• Men and women of childbearing age must be willing to use effective contraception while on treatment and for at least 5 months thereafter
• Presence of at least one site of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors 1.1
• Ability to provide written, informed consent. Legally authorized representatives are permitted
• Negative human immunodeficiency virus (HIV) test at screening, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count 200/uL, and have an undetectable viral load
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening * Note: The HBV DNA test will be performed only for patients who have a negative HBsAg test and a positive total HBcAb test
• Patient with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

Exclusion Criteria

• Presence of an Food and Drug Administration (FDA) approved targeted therapy for patients with lung non-small cell carcinoma (NSCLC) harboring a genomic aberration for which an FDA-approved targeted therapy is indicated
• Hypersensitivity to platinum agents
• Patients with ≥ grade 2 peripheral neuropathy
• Prior use of tumor necrosis factor-alpha (TNF-a) inhibitor
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment. * Note: this exclusion criteria has the following exceptions: ** Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after principal investigator confirmation has been obtained ** Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study ** Topical steroids
• Active or history of autoimmune disease or immune deficiency including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis, antiphospholipid antibody syndrome Wegener granulomatosis, Sjogren syndrome, Guillain-Barré syndrome, or multiple sclerosis * Note: This exclusion criteria has the following exceptions: ** Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study ** Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study ** Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: *** Rash must cover < 10% of body surface area *** Disease is well controlled at baseline and requires only low-potency topical corticosteroids *** No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan * Note: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Baseline hearing deficit (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0 grade 2 or higher)
• Ongoing bacterial, viral, or antifungal infection requiring antimicrobial treatment with the exception of thrush
• Active tuberculosis or untreated, latent tuberculosis * Note: If a patient has signs, symptoms, or a history suggestive of active tuberculosis, evaluation by an infectious disease physician will be required and active tuberculosis ruled-out prior to enrollment
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, or cerebrovascular accident) within 3 months prior to initiation of study treatment, or unstable arrhythmia * Note: Patients are ineligible if they have a history of myocardial infarction or unstable angina within the past 12 months
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• Known HIV infection requiring antiretroviral medications and those with acquired immunodeficiency syndrome (AIDS)
• Acute or chronic Hepatitis B or C infection
• Active herpes zoster infection
• Current treatment with anti-viral therapy for HBV
• Non-healed infected skin ulcers
• Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5mmol/L, calcium > 12mg/dL or corrected serum calcium > ULN)
• Prior history of other malignancy with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, Stage I uterine cancer, localized prostate cancer, nonmelanomatous skin cancer, ductal carcinoma or lobular carcinoma in situ of the breast
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment * Note: Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
• Prior allogeneic stem cell or solid organ transplantation
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Live, attenuated vaccines (e.g., FluMist) are prohibited within 4 weeks prior to initiation of study treatment, during treatment with nivolumab, and for 5 months after the last dose of nivolumab
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the nivolumab formulation
• Known allergy or hypersensitivity to any component of the certolizumab pegol formulation
• Known allergy or hypersensitivity to any component of the platinum based chemotherapy formulations
• Known allergy or hypersensitivity to any component of the taxanes chemotherapy formulations
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of nivolumab, within 3 months after the final dose of certolizumab pegol, and within 6 months after the final dose of carboplatin, cisplatin, pemetrexed or gemcitabine treatment