A Platform Study in Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria:

• Participants with confirmed squamous or non-squamous NSCLC with a current Stage IVmNSCLC.

• Provision of acceptable archival tumour tissue (or fresh tumour tissue biopsy ifarchival tumour tissue is not available and if clinically feasible) is mandatory atscreening.

• Measurable disease as defined by at least one lesion that can be accurately measuredat baseline as ≥ 10 mm at the longest diameter.

• Minimum life expectancy of 12 weeks in the opinion of the investigator.

• Adequate organ and marrow function.

• Contraceptive use by male or female participants should be consistent with localregulations regarding the methods of contraception for those participating inclinical studies.

• Adequate organ and marrow function.

Inclusion Criteria for Sub Study 2:

• Programmed death-ligand 1 (PD-L1) tumour proportion score (TPS) ≥ 1% (per localreport).

• Adequate coagulation and urinalysis.

• Minimum body weight of 30 kg.

Exclusion Criteria:

• Participants with epidermal growth factor receptor mutations, anaplastic lymphomareceptor fusions or any other known genomic alteration for which targeted therapy isapproved in the first line per local standard of care.

• Presence of small cell and neuroendocrine histology components.

• Any severe or uncontrolled systemic diseases, including uncontrolled hypertension,and active bleeding diseases, ongoing or active known infection; interstitial lungdisease/pneumonitis (of any grade); unstable and/or symptomatic venousthromboembolism, serious chronic gastrointestinal conditions associated withdiarrhoea, active non-infectious skin disease or substance abuse.

• Has had a prior stem cell, bone marrow, allogenic tissue, or solid organ transplant.

• Has an active autoimmune disease that has required systemic treatment in the past 5years.

• History of clinically significant arrhythmia, cardiomyopathy of any aetiology orsymptomatic congestive heart failure.

• History of another primary malignancy except for malignancy treated with curativeintent with no known active disease ≥ 2 years before the first dose of studyintervention or presence of small cell and neuroendocrine histology components.

• Persistent toxicities (common terminology criteria for adverse events [CTCAE] ≥Grade 2) caused by previous anti-cancer therapy, excluding alopecia.

• Spinal cord compression or symptomatic brain metastases.

• Treatment with any other anti-cancer agents or immunosuppressive medication.

• Palliative radiotherapy with a limited field of radiation within 2 weeks or with awide field of radiation or to more than 30% of the bone marrow within 4 weeks, priorto the first dose of study intervention.

Exclusion Criteria for Sub Study 2:

• Known active hepatitis A.

• Acute hepatitis B infection (anti-hepatitis B core antibody [HBc] immunoglobulin M [IgM] positive) or chronic hepatitis B infection with HBV DNA ≥ 2000 IU/mL.

• Active hepatitis C infection (anti-HCV positive with HCV RNA detectable) or anti-HCV positive with HCV RNA undetectable for less than 12 weeks following treatmentfor HCV.

• Known human immunodeficiency virus (HIV) infection that is not well controlled.

• Evidence of Grade ≥ 1 central nervous system (CNS) haemorrhage.

• Uncontrolled arterial hypertension ≥ 150 mm Hg (systolic) and/or ≥ 100 mm Hg (diastolic).

• Has radiologically documented evidence of major blood vessel invasion or encasementby cancer, or major airway invasion by cancer or intra-tumour cavitation.

• Has experienced any arterial thrombotic event, a Grade ≥ 3 bleeding event or hasgross haemoptysis.

• Has significant bleeding disorders, serious or nonhealing wound, ulcer or clinicallyrelevant congestive heart failure.

• Has a bowel obstruction, history or presence of inflammatory enteropathy orextensive intestinal resection.

• Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis (any degree) and ahistory of hepatic encephalopathy or clinically meaningful ascites resulting fromcirrhosis.

• Prior systemic therapy received for advanced or mNSCLC.

• Prior exposure to an anti-T-cell immunoreceptor with Ig and ImmunoreceptorTyrosine-based Inhibition Motif domains (TIGIT) therapy or immune-oncology agentsuch as anti-programmed cell death protein 1 (PD-1), anti-PD-L1, or anti-cytotoxicT-lymphocyte associated antigen 4 (CTLA-4), or any other anti-cancer therapytargeting immune-regulatory receptors or mechanisms.

• Chronic therapy with antiplatelet agents.

• Prior exposure to anti-vascular endothelial growth factor (VEGF) therapy.

• Medical contraindication to protocol-specified platinum doublet regimens orramucirumab.

• Known allergy or hypersensitivity to rilvegostomig or any of the excipients ofrilvegostomig, cisplatin, carboplatin, paclitaxel or nab-paclitaxel or pemetrexed orramucirumab.