Adding Tumor Treating Fields Therapy to Chemoradiation and Durvalumab for the Treatment of Patients with Locally Advanced Stage III Non-Small Cell Lung Cancer

Inclusion Criteria

• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Subject aged >= 22 years
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Clinical American Joint Committee on Cancer (AJCC) (AJCC, 8th edition [ed.]) stage IIIA, IIIB or IIIC NSCLC with unresectable disease. Staging Fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/CT and magnetic resonance imaging (MRI) brain (preferred) or CT head with contrast scan must have been completed within 60 days prior to initiation of chemoradiotherapy (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
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Able to operate the NovoTTF-200T System independently or with the help of a caregiver
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Eligible to receive standard of care chemoradiation per institutional standards
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Subject must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria by CT
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Absolute neutrophil count (ANC) >= 1500/mm^3
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Platelet count >= 100,000/mm^3
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Hemoglobin >= 10 g/dL (transfusions are allowed for device duration level 2 only if anemia is due to prior therapy)
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) or direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional ULN * Subjects with liver metastases will be allowed to enroll with AST and ALT levels =< 5 x ULN
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Estimated creatinine clearance >= 50 mL/min by Cockcroft-Gault formula
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: 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)
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Subjects of childbearing potential and subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception
• PRE-CHEMORADIATION PHASE INCLUSIVE CRITERIA: Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: The subject must have previously completed and been eligible for step 1 registration
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: Completion of post-chemoradiation CT scan and RECIST 1.1 assessment
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: Eligible to receive consolidation immunotherapy per institutional standards and Investigator judgement
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: Able to operate the NovoTTF-200T System independently or with the help of a caregiver
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: ECOG performance status =< 1
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: Absolute neutrophil count (ANC) >= 1500/mm^3
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: Platelet count >= 100,000/mm^3
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: Hemoglobin >= 10 g/dL (transfusions are allowed for device duration level 2 only if anemia is due to prior therapy with concurrent chemoradiation.)
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: Total Bilirubin =< 1.5 x institutional upper limit of normal (ULN) or direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: AST(SGOT)/ALT(SGPT) =< 3 x institutional ULN * Subjects with liver metastases will be allowed to enroll with AST and ALT levels=< 5 x ULN
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: Estimated creatinine clearance >= 50 mL/min by Cockcroft-Gault formula
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 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
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE INCLUSION CRITERIA: Resolution of any pneumonitis from prior radiation therapy to < grade 1 per the treating investigator

Exclusion Criteria

• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: Prior thoracic radiation, including breast radiation
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: Prior exposure to TTFields
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: Prior systemic immunotherapy or radiotherapy for NSCLC
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: Known underlying skin hypersensitivity or known allergy to skin adhesives or hydrogel
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: Known hypersensitivity to radiation due to genetic susceptibility, connective tissue disease, or any other cause
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: Receiving other investigational agents
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: 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
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: 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)
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: 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.)
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: Known human immunodeficiency virus (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
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: Active known infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [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 ribonucleic acid (RNA)
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: 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
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: History of allogeneic stem cell or solid organ transplantation
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: 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
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: 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)
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: Subjects taking prohibited medications. 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
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: History of exudative pleural effusions, regardless of cytology
• PRE-CHEMORADIATION PHASE EXCLUSION CRITERIA: Peripheral neuropathy > grade 1 for patients receiving concurrent carboplatin and paclitaxel with radiation
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE EXCLUSION CRITERIA: Subjects who in the investigators opinion had disease progression following concurrent chemoradiation
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE EXCLUSION CRITERIA: Known underlying skin hypersensitivity or known allergy to skin adhesives or hydrogel
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE EXCLUSION CRITERIA: Major surgery (per treating investigator) 4 weeks prior to starting study drug or who have not fully recovered from major surgery
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE EXCLUSION CRITERIA: 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.)
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE EXCLUSION CRITERIA: 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
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE EXCLUSION CRITERIA: History of allogenic stem cell or solid organ transplantation
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE EXCLUSION CRITERIA: 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
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE EXCLUSION CRITERIA: 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
• PRE-CONSOLIDATIVE IMMUNOTHERAPY PHASE EXCLUSION CRITERIA: History of exudative pleural effusions, regardless of cytology