The study is a prospective, randomized controlled phase III trial aimed to test the efficacy and safety of TTFields, using the NovoTTF-200T device, concurrent with standard therapies for stage 4 NSCLC patients, following progression while on or after platinum based treatment. The device is an experimental, portable, battery operated device for chronic administration of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor, by means of surface, insulated electrode arrays.

DEVICE: NovoTTF-200T

Patients receive continuous TTFields treatment using the NovoTTF-200T device. TTFields treatment will consist of wearing four electrically insulated electrode arrays on the chest. The treatment enables the patient to maintain regular daily routine.

Other Name: TTFields

Drug: Immune checkpoint inhibitors or docetaxel Patients receive standard of care with Immune checkpoint inhibitors or docetaxel

DRUG: Immune checkpoint inhibitors or docetaxel

Patients receive standard of care with Immune checkpoint inhibitors or docetaxel

• To compare OS in subjects treated with TTFields concomitant with pembrolizumab and platinumbased chemotherapy compared to OS of those treated with pembrolizumab and platinum-based chemotherapy alone (superiority analysis)

• To compare PFS per RECIST v1.1 as assessed by BICR, in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy compared to PFS of those treated with pembrolizumab and platinum-based chemotherapy alone (superiority analysis)

1. 22 years of age and older (some regional variations to inclusion age exist)

2. Life expectancy of ≥ 3 months

3. Histological diagnosis of squamous or non-squamous, inoperable, metastatic NSCLC

4. Diagnosis of radiological progression while on or after first platinum-based systemic therapy administered for advanced or metastatic disease.

   1. Patients who received adjuvant or neoadjuvant platinum-based chemotherapy (after surgery and/or radiation therapy) and developed metastatic disease within 6 months of completing therapy are eligible.
   2. Patients with metastatic disease more than 6 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum- based regimen given to treat the advanced or metastatic disease, are eligible.
   3. Patients should not receive any systemic therapy after platinum failure before enrollment into the study. Maintenance therapy after platinum based therapy and prior to progression is allowed.

5. ECOG Score of 0-2

6. Assigned by the physician to receive either docetaxel or immune checkpoint inhibitor per standard of care regimen

7. Able to operate the NovoTTF-200T device independently or with the help of a caregiver

8. Signed informed consent for the study protocol

1. Metastases to central nervous system (CNS) with clinical symptoms or evidence of new metastases to CNS during screening. Patients who previously received treatments for the metastases to CNS, are stable and meet the following requirements are allowed to be enrolled:

   1. The patients are neurologically returned to baseline (except for residual signs or symptoms related to CNS treatment).
   2. No treatment for the metastases to CNS during the screening period (e.g. surgery, radiotherapy, corticosteroid therapy- prednisone > 10 mg/day or equivalent).
   3. No progress in CNS lesions as indicated by MRI within 14 days prior to randomization.
   4. No meningeal metastasis or spinal cord compression.

2. Patients planned to receive immune checkpoint inhibitor with contra-indications to receive immunotherapy

3. Patients planned to receive docetaxel with contra-indications to receive docetaxel

4. Severe comorbidities:

   1. Clinically significant (as determined by the investigator) hematological, hepatic and renal dysfunction, defined as: Neutrophil count < 1.5 x 10^9/L and platelet count < 100 x 10^9/L; bilirubin > 1.5 x ULN; AST and/or ALT > 2.5 x ULN or > 5 x ULN if patient has documented liver metastases; and serum creatinine > 1.5 x ULN
   2. History of significant cardiovascular disease unless the disease is well controlled. Significant cardiac disease includes second/third degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of the New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary activity results in fatigue, palpitation or dyspnea)
   3. History of arrhythmia that is symptomatic or requires treatment. Patients with atrial fibrillation or flutter controlled by medication are not excluded from participation in the trial
   4. History of pericarditis
   5. History of interstitial lung disease
   6. History of cerebrovascular accident (CVA) within 6 months prior to randomization or that is not stable
   7. Active infection or serious underlying medical condition that would impair the ability of the patient to received protocol therapy
   8. History of any psychiatric condition that might impair patient's ability to understand or comply with the requirements of the study or to provide consent
   9. Any other malignancy requiring anti-tumor treatment in the past three years, excluding treated stage I prostate cancer, in situ cervical cancer, in situ breast cancer and non-melanomatous skin cancer

5. Concurrent treatment with other experimental treatments for NSCLC while on the study

6. Implantable electronic medical devices (e.g. pacemaker, defibrillator) in the upper torso

7. Known allergies to medical adhesives or hydrogel

8. Pregnancy or breast-feeding (patients with reproductive potential must use effective contraception methods throughout the entire study period, as determined by their investigator/gynecologist)

9. Admitted to an institution by administrative or court order