An open label, phase 3, randomized clinical trial

Arm 1: pembrolizumab alone (200mg fixed dose, 3 weekly) until progressive disease (PD)

Arm 2: pembrolizumab (200mg fixed dose, 3 weekly) with chemotherapy (carboplatin AUC 5 or cisplatin (75 or 80mg/m2) combined with either pemetrexed (500mg/m2, non-squamous) or paclitaxel (200mg/m2, squamous). Chemotherapy doublets will be given for 2-4 cycles depending on the tumor response, also, pemetrexed and pembrolizumab will continued as maintenance until PD or unacceptable toxicity in arm 2

ORR, as defined by partial response (PR) and complete response (CR) at week 6

Disease control rate (DCR), as defined by stable disease (SD) and PR and CR at week 6

Histologically confirmed NSCLC, negative for EGFR mutations and ALK fusions, no molecular testing is required in squamous NSCLC

ECOG Performance Scale 0-2

Be willing and able to provide written informed consent for the trial

Be 18 years or older of age on the day of signing informed consent

Have measurable disease based on RECIST v1.1

Must provide tissue from a histological tumor biopsy that was not yet irradiated

High tumor PD-L-1 expression (≥50% TPS)

High tumor burden (≥2 extra pulmonary metastases (M1c)) and not amenable for local consolidative therapies

Patients amenable for local consolidative therapies

Use of steroids equivalent to >10 mg prednisolon per day prior to start of study or other immunosuppressive medications within 14 days prior. Inhaled or topical steroids, and adrenal replacement steroid >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease

Untreated brain metastases

Uncontrolled active infections, HIV, active Hepatitis B or C

Autoimmune diseases and interstitial lung diseases are to be excluded depending on physicians decision