A Study of Tislelizumab in Combination With Investigational Agents in Participants With Non-Small Cell Lung Cancer

Key 1. Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), including nonsquamous or squamous subtypes, that is either locally advanced or recurrent and not eligible for curative surgery and/or definitive chemoradiotherapy, or metastatic NSCLC. 2. No prior systemic therapy administered as the primary treatment for metastatic NSCLC. Prior adjuvant or neoadjuvant chemotherapy, definitive chemoradiation, or adjuvant radiotherapy for locally advanced disease is permitted, provided the last dose of chemotherapy and/or radiotherapy occurred at least 6 months prior to randomization/enrollment. 3. Tumor programmed death-ligand 1 (PD-L1) expression must be evaluable, as determined by a local or central laboratory using archival tumor tissue or a fresh biopsy. Participants with unknown PD-L1 expression are not eligible. 4. At least one measurable lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Key

• 1. Diagnosis of mixed small cell lung cancer. 2. Known genomic alterations for which effective targeted therapies are available according to local standard of care, including but not limited to:
• Epidermal growth factor receptor (EGFR) mutations
• Anaplastic lymphoma kinase (ALK) rearrangements
• B-Raf proto-oncogene (BRAF) mutations
• Rearranged during transfection (RET) fusions
• c-ros oncogene 1 (ROS1) rearrangements 3. Participants with nonsquamous NSCLC and unknown EGFR mutation status must undergo local testing. Those found to have EGFR-sensitizing mutations will be excluded. 4. Prior treatment with immune-based therapies that target immune checkpoint pathways, including:
• PD-1 (programmed cell death protein 1) inhibitors
• PD-L1 (programmed death-ligand 1) inhibitors
• PD-L2 (programmed death-ligand 2) inhibitors
• TIGIT (T cell immunoreceptor with Ig and ITIM domains) inhibitors
• LAG-3 (lymphocyte activation gene 3) inhibitors 5. Participants previously treated with these agents in a neoadjuvant, adjuvant, or consolidation setting may be eligible if a treatment-free interval of at least 6 months has elapsed since the last dose and radiologic evidence of recurrence is present. 6. Use of Chinese herbal medicines or Chinese patent medicines intended for cancer control within 14 days prior to randomization/enrollment. 7. Presence of active leptomeningeal disease, untreated or uncontrolled brain metastases, or active autoimmune disease. Note: Additional protocol-defined and sub-study-specific criteria may apply.