Tumor Treating Fields for Locally Advanced NSCLC

Inclusion Criteria: Step 1: Pre-Chemoradiation Inclusion Criteria * Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC). * Clinical AJCC (AJCC, 8th ed.) stage IIIA or IIIB, or IIIC NSCLC with unresectable disease. Staging FDG-PET/CT and MRI brain (preferred) or CT head with contrast scan must have been completed within 60 days prior to initiation of concurrent CRT. Unresectable disease must be determined by a multi-disciplinary team unless, in the opinion of the treating investigator, the subject's disease is clearly unresectable. Subjects who refuse surgery will be considered to have unresectable disease. * Able to operate the NovoTTF-200T System independently or with the help of a caregiver. * Eligible to receive standard of care chemoradiation per institutional standards. * Subject must have measurable disease by RECIST 1.1 criteria by CT. * ECOG Performance Status ≤ 1. * Adequate organ function as defined as: * Hematologic: * Absolute neutrophil count (ANC) ≥ 1500/mm3 * Platelet count ≥ 100,000/mm3 * Hemoglobin ≥ 10 g/dL (transfusions are allowed for Device Duration Level 2 only if anemia is due to prior therapy.) * Hepatic: * Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN) or direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN. * AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN * Subjects with liver metastases will be allowed to enroll with AST and ALT levels ≤ 5 x ULN. * Renal: * Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula: * Males: * ((140-age)×weight\[kg\])/(serum creatinine \[mg/dL\]×72) * Females: * (((140-age)×weight\[kg\])/(serum creatinine \[mg/dL\]×72))×0.85 * For subjects of childbearing potential: * Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Subjects \< 50 years of age: * Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and * Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or * Underwent surgical sterilization (bilateral oophorectomy or hysterectomy). * Subjects ≥ 50 years of age: * Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or * Had radiation-induced menopause with last menses \>1 year ago; or * Had chemotherapy-induced menopause with last menses \>1 year ago; or * Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy). * Subjects of childbearing potential and subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception as described in Section 4.6. * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Step 2: Pre-Consolidative Immunotherapy Phase Inclusion Criteria * The subject must have previously completed and been eligible for Step 1 registration. * Completion of post-chemoradiation CT scan and RECIST 1.1 assessment. * Eligible to receive consolidation immunotherapy per institutional standards and Investigator judgement. * Able to operate the NovoTTF-200T System independently or with the help of a caregiver. * ECOG Performance Status ≤ 1. * Adequate organ function as defined as: * Hematologic: * Absolute neutrophil count (ANC) ≥ 1500/mm3 * Platelet count ≥ 100,000/mm3 * Hemoglobin ≥ 10 g/dL (transfusions are allowed for Device Duration Level 2 only if anemia is due to prior therapy with concurrent chemoradiation.) * Hepatic: * Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN) or direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN. * AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN * Subjects with liver metastases will be allowed to enroll with AST and ALT levels ≤ 5 x ULN. * Renal: * Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula: * Males: * ((140-age)×weight\[kg\])/(serum creatinine \[mg/dL\]×72) * Females: * (((140-age)×weight\[kg\])/(serum creatinine \[mg/dL\]×72))×0.85 * Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior cancer therapy (except for alopecia or fatigue) unless considered clinically not significant and/or stable by the treating investigator. * Resolution of any pneumonitis from prior radiation therapy to \< grade 1 per the treating investigator. Exclusion Criteria: Step 1: Pre-Chemoradiation Phase Exclusion Criteria * Prior thoracic radiation, including breatbreast radiation. * Prior exposure to TTFields. * Prior systemic immunotherapy or radiotherapy for NSCLC. * nown underlying skin hypersensitivity or known allergy to skin adhesives or hydrogel. * Known hypersensitivity to radiation due to genetic susceptibility, connective tissue disease, or any other cause. * Receiving other investigational agents. * Major surgery (per treating investigator) within 4 weeks prior to starting study drug or who have not fully recovered from major surgery. Note: Biopsies without significant complications will not be considered major surgery. * The diagnosis of another malignancy within ≤ 2 years before study enrollment, except for those considered to be adequately treated with no evidence of disease or symptoms and/or will not require therapy during the study duration (i.e., basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix, or low-grade prostate cancer with Gleason Score ≤ 6). * Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions: * Cardiovascular disorders: * Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious or clinically significant cardiac arrhythmias. * Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before the first dose. * QTc prolongation defined as a QTcF \> 500 ms. * Known congenital long QT. * Left ventricular ejection fraction \< 50%. * Uncontrolled hypertension defined as persistent blood pressure of ≥ 160/90 as assessed from the mean of three consecutive blood pressure measurements taken over 10 minutes. * Implanted pacemaker, defibrillator or other electrical medical devices; * Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[subjects may not receive the drug through a feeding tube\], social/ psychological issues, etc.) * Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment. Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial. * Active known infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C. Note: Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. * Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study. * History of allogenic stem cell or solid organ transplantation * Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, uveitis, etc.\]). The following are exceptions to this criterion: * Patients with vitiligo or alopecia * Patients with endocrine disorders with controlled disease on hormone replacement therapy (e.g. adrenal, thyroid, or pituitary replacement therapy) * Any chronic skin condition that does not require systemic therapy * Patients without active disease in the last 5 years may be included but only after consultation with the principal investigator. * Patients with celiac disease controlled by diet alone * Current or prior use of immunosuppressive medication within 14 days of cycle one day one, EXCEPT for the following permitted steroids: * Intranasal, inhaled, topical steroids, eye drops, or local steroid injection (e.g., intra-articular injection); * Systemic corticosteroids at physiologic doses ≤ 10mg/day of prednisone or equivalent; * Steroids as premedication for hypersensitivity reactions (e.g., computed tomography (CT) scan premedication). * Subjects taking prohibited medications as described in Section 5.11. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment. * History of exudative pleural effusions, regardless of cytology. * Peripheral neuropathy \> grade 1 for patients receiving concurrent carboplatin and paclitaxel with radiation. Step 2 Pre-Consolidative Immunotherapy Phase Exclusion Criteria * Subjects who in the investigators opinion had disease progression following concurrent chemoradiation. * Known underlying skin hypersensitivity or known allergy to skin adhesives or hydrogel. * Major surgery (per treating investigator) 4 weeks prior to starting study drug or who have not fully recovered from major surgery. * Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions: * Cardiovascular disorders: * Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious or clinically significant cardiac arrhythmias. * Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before the first dose. * QTc prolongation defined as a QTcF \> 500 ms. * Known congenital long QT. * Left ventricular ejection fraction \< 50%. * Uncontrolled hypertension defined as persistent blood pressure of ≥ 160/90 as assessed from the mean of three consecutive blood pressure measurements taken over 10 minutes. * Implanted pacemaker, defibrillator or other electrical medical devices; * Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[subjects may not receive the drug through a feeding tube\], social/ psychological issues, etc.) * Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study. * History of allogenic stem cell or solid organ transplantation * Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, uveitis, etc.\]). * The following are exceptions to this criterion: * Patients with vitiligo or alopecia * Patients with endocrine disorders with controlled disease on hormone replacement therapy (e.g. adrenal, thyroid, or pituitary replacement therapy) * Any chronic skin condition that does not require systemic therapy * Patients without active disease in the last 5 years may be included but only after consultation with the principal investigator * Patients with celiac disease controlled by diet alone. * Current or prior use of immunosuppressive medication within 14 days of cycle one day one, EXCEPT for the following permitted steroids: * Intranasal, inhaled, topical steroids, eye drops, or local steroid injection (e.g., intra-articular injection) * Systemic corticosteroids at physiologic doses ≤ 10mg/day of prednisone or equivalent * History of exudative pleural effusions, regardless of cytology.