Inclusion Criteria:
1. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study
2. Histologically confirmed and treatment-naïve non-small cell lung cancer UICC 9th stage IV
3. PD-L1 ≥ 50%
4. High Tumor Burden defined as the longest diameter of the tumor or at least one metastasis ≥ 50mm and no eligibility for a curative treatment approach
5. Measurable disease according to RECIST v1.1
6. No actionable genomic alterations (AGA) qualifying for targeted first-line treatment
7. Eligible for platinum-based chemoimmunotherapy
8. Age ≥18 years
9. Patients with brain metastases may be included, except when whole brain radiation therapy (WBRT) is pending. In such case, patients may be included 7 or more days after completion of WBRT.
10. Female subjects of childbearing potential (FOCBP) should be using highly effective contraceptive measures and must have a negative urine or serum pregnancy test within 7 days prior to start of study treatment and must not be breast-feeding prior to start of trial. Non-child-bearing potential must be evidenced by fulfilling one of the following criteria at screening:
* Postmenopausal, defined as at least 12 months with no menses without an alternative medical cause; a follicle stimulating hormone (FSH) level in the postmenopausal range for the institution may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
* have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, at least 6 weeks prior to screening (Women with tubal ligation are still considered of child-bearing potential according to CTFG Guidance).
* have a congenital or acquired condition that prevents childbearing Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
Exclusion Criteria:
1. Presence of a condition, disease or abnormality that in the opinion of the Investigator would compromise the safety of the patient, the patient's ability to comply with the study procedures (e.g., dementia) or the quality of the data. Specifically, the presence of any preexisting autoimmune disease that prohibits dosing of IMP as per treatment modification guidelines in the current IB/SmPC
2. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study
3. Concurrent malignancy other than NSCLC requiring active treatment
4. Has known hypersensitivity to the IMPs or to any component of the planned regimen, their metabolites, or formulation excipients, or any other contraindication to any component of the planned study regimen according to the tislelizumab IB and the relevant SmPCs
5. Current use of systemic corticosteroids that exceed 10 mg/day of prednisone or is equivalent medication within 3 days before the first dose of tislelizumab/pembrolizumab, except the following criterion:
\- steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
6. Female subjects who are pregnant or breast-feeding or patients of reproductive potential who are not employing a highly effective method of birth control (failure rate of less than 1% per year)
7. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities
8. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts
