A study designed to evaluate the efficacy and safety of BGB-A1217 + tislelizumab compared with that of pembrolizumab in patients with PD-L1-selected NSCLC who have locally advanced or recurrent disease that is unresectable or not amenable to radiotherapy, with or without chemoradiotherapy, or previously untreated metastatic disease, and whose tumors do not harbor EGFR-sensitizing mutations or ALK translocations. The efficacy and safety of tislelizumab alone will be explored in a small cohort of the same patient population.

You will have the following exams, tests, or procedures done: Measurement of your height, weight, and vital signs (blood pressure, respiratory rate, pulse, and temperature) Complete physical exam Blood sample collection for the following tests: Safety laboratory tests. This may include routine tests and special blood chemistries, blood clotting, and blood counts to evaluate your overall health and thyroid, liver, pancreas, and kidney, and heart functions. Additional blood samples may be collected to perform routine blood tests, if your study doctor thinks it is necessary. Enzymes tests to check your muscle and heart function (Creatine kinase [CK] and creatine kinase muscle/brain [CK MB] isoenzyme or Troponin I or Troponin T) You will be tested for HIV, Hepatitis B virus and hepatitis C virus to check whether you are infected with these viruses. If a test shows that you have an active hepatitis B or C infection or HIV, you will have follow-up counselling and medical advice provided by the study doctor or study staff. If your test results are positive, you will be notified and the study doctor will be required by law to notify government health authorities. Signing this consent form means that you agree to have this testing. Urine sample collection for routine safety tests. If you are a woman and are able to become pregnant, you will have a urine or serum pregnancy test (must be negative to enter the study). An electrocardiogram (ECG) to look at the electrical activity of your heart. Pulmonary function test to check how your lungs are working and completion of questionnaires about your general health, well-being, and overall quality of life. Imaging to assess your tumor before starting treatment. A computerized series of x-rays (CT scan or Computed Tomography) will be performed. A series of pictures of the inside of your body created by magnetic energy (MRI scan or magnetic resonance imaging) may be done if a CT scan is not available or if this is considered a more appropriate test for your cancer by the study doctor. In addition, an MRI or CT of the head will be done to determine if there is any spread of the cancer to your brain. A type of imaging that uses a radioactive substance called tracer to look at your body (whole-body positron emission tomography (PET)/CT scan) or a bone scan may also be performed if your study doctor decides to do so. Rarely, color photography may be used to document skin metastases if you have any.