A Study of Belrestotug Plus Dostarlimab Compared With Placebo Plus Pembrolizumab in Previously Untreated Participants With Programmed Death Ligand 1 (PD-L1) High Non-small-cell Lung Cancer (NSCLC)

Prior treatment

• Has had surgery within 4 weeks of the first dose of study intervention and has not recovered from AEs (i.e., has any ongoing surgery-related events ≥ Grade 1)/complications related to surgery or has received lung radiation therapy of \>30 gray (Gy) within 6 months
• Has received any live vaccine within 30 days prior to first dose of study intervention.
• Has severe infection or complication thereof 4 weeks prior to randomisation including active tuberculosis.

Other illness

• Has an invasive malignancy or history of invasive malignancy other than the disease under study within the last 5 years, with the exception of those with a negligible risk of metastasis or death and/or treated with expected curative outcome.
• Has symptomatic, untreated, or actively progressin g brain metastases or leptomeningeal disease
• Has autoimmune disease or syndrome (current or history thereof) that required systemic treatment within the past 2 years.
• Has any history of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis.
• Has active inflammatory bowel disease
• Has a history of significant acute or chronic cardiac diagnosis requiring intervention/treatment in the last 6 months.
• Has a history of allogeneic tissue/stem cell transplant or solid organ transplant.

Lab values

• Has NSCLC with a tumor that harbors any of the following molecular alterations:
  • Epidermal growth factor receptor (EGFR) mutations that are sensitive to available targeted inhibitor therapy
  • Anaplastic lymphoma kinase (ALK) translocations that are sensitive to available targeted inhibitor therapy
  • Any other known genomic aberrations or oncogenic driver mutations for which a locally approved targeted therapy is available for first line treatment of locally advanced or metastatic NSCLC.
• Has received prior therapy with any immune checkpoint inhibitors, including antibodies or drugs targeting PD-(L)1, Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), or other checkpoint pathways.

Other

• Has never smoked, defined as smoking \<100 tobacco cigarettes in a lifetime.
• Has symptomatic ascites, pleural effusion, or pericardial effusion.

• Has a histologically or cytologically confirmed diagnosis of locally advanced, unresectable NSCLC (not eligible for curative surgery and/or definitive radiotherapy with or without chemotherapy), or Metastatic NSCLC
• Has not received prior systemic therapy for their locally advanced or metastatic NSCLC.
• Provides a fresh tumor tissue sample obtained at the time of or after the initial diagnosis of locally advanced or metastatic NSCLC.
• Has a PD-L1-high (Tumor cells \[TC\] ≥50%) tumor
• Has measurable disease (at least 1 target lesion) based on RECIST 1.1
• Has an Eastern Cooperative Oncology Group (ECOG) Performance status (PS) score of 0 or 1.
• Has adequate organ function