A Global Phase III Study of Rilvegostomig or Pembrolizumab Monotherapy for First-Line Treatment of PD-L1-high Metastatic Non-small Cell Lung Cancer

Inclusion Criteria:

• Histologically or cytologically documented NSCLC (non small lung cancer), includingall histological subtypes.

• Stage IV mNSCLC (metastatic non-small cell lung cancer) (based on the American JointCommittee on Cancer Edition 8) not amenable to curative treatment.

• Absence of sensitizing EGFR (epidermal growth factor) mutations and ALK (anaplasticlymphoma kinase) and ROS1 (c-ros oncogene 1) rearrangements. Negative assay resultis required for all non-squamous histology subtypes.

• Absence of documented tumor genomic mutation results from tests conducted as part ofstandard local practice in any other actionable driver oncogenes for which there arelocally approved targeted 1L (first line) therapies.

• WHO (World Health Organization)/ECOG (Eastern Cooperative Oncology Group)performance status of 0 or 1, with no deterioration over the previous 2 weeks priorto baseline at screening and prior to randomization.

• Minimum life expectancy of 12 weeks.

• Provision of acceptable tumor sample for the central testing prior to randomization.

• At least one lesion not previously irradiated that qualifies as a RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, Version 1.1) TL (target lesion) atbaseline and can be accurately measured at baseline as ≥ 10 mm in the longestdiameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT (computedtomography) or MRI (magnetic resonance imaging) and is suitable for accuraterepeated measurements.

• Adequate organ and bone marrow function

Exclusion Criteria:

• As judged by the investigator, any severe or uncontrolled systemic diseases, makesit undesirable for the participant to participate in the study or that wouldjeopardize compliance with the protocol.

• History of organ transplant.

• Active or prior documented autoimmune or inflammatory disorders requiring chronictreatment with steroids or other immunosuppressive treatment.

• History of another primary malignancy except for malignancy treated with curativeintent with no known active disease ≥ 2 years before the first dose of studyintervention and of low potential risk for recurrence.

• Presence of small cell and neuroendocrine histology components.

• Brain metastases unless asymptomatic, stable, and not requiring steroids oranticonvulsants for at least 4 weeks prior to start of study intervention.

• Active primary immunodeficiency/active infectious disease(s)

• Active tuberculosis infection

• Any prior systemic therapy received for advanced or mNSCLC (metastatic non-smallcell lung cancer).

• Any prior exposure to an anti-TIGIT (T-cell immunoglobulin and immunoreceptortyrosine-based inhibitory motif domain) therapy or any other anticancer therapytargeting immune-regulatory receptors or mechanisms.

• Any prior treatment with an anti-PD-1 (programmed cell death protein 1) oranti-PD-L1 (anti-programmed death-ligand 1) agent.