The goal of this clinical study is to learn more about the study drug, sacituzumab govitecan-hziy (SG), and its dosing in combination with pembrolizumab or pembrolizumab and a platinum agent (carboplatin or cisplatin), in participants with advanced or metastatic (cancer that has spread) non-small-cell lung cancer (NSCLC).

Key Inclusion Criteria:

• Individuals with pathologically documented evidence of Stage IV non-small cell lung Cancer (NSCLC) disease at the time of enrollment
• Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per RECIST Version 1.1 criteria by investigator
• No prior systemic treatment for metastatic NSCLC
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Adequate hematologic counts
• Adequate hepatic function

Key Exclusion Criteria:

• Mixed SCLC and NSCLC histology
• Active second malignancy
• NSCLC that is eligible for definitive local therapy alone
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has had an allogenic tissue/solid organ transplant.
• Has severe (≥ Grade 3) hypersensitivity to SG, pembrolizumab, carboplatin, or cisplatin, their metabolites, or formulation excipient
• Has received radiation therapy to the lung
• Individuals may not have received systemic anticancer treatment within the previous 6 months
• Is currently participating in or has participated in a study of an investigational agent
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
• Known active central nervous system (CNS) metastases
• History of cardiac disease
• Active chronic inflammatory bowel disease
• Active serious infection requiring antibiotics
• Active or chronic hepatitis B infection
• Positive hepatitis C antibody
• Positive serum pregnancy test or women who are lactating

Note: Other protocol defined Inclusion/Exclusion criteria may apply.