Volrustomig Priming Regimens Exploratory Phase II Platform Study

Prior treatment

• Active or prior documented autoimmune or inflammatory disorders.
• Brain metastases unless asymptomatic, stable, and not requiring steroids for at least 14 days prior to start of study intervention. A minimum of 2 weeks must have elapsed between the end of radiation therapy and study enrollment.
• Prior chemotherapy or any other systemic therapy for Stage IV NSCLC. Participants who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for local disease are eligible, provided that progression has occurred greater (\>) 12 months from end of last therapy.

Other illness

• History of primary active immunodeficiency.
• Mixed small-cell lung cancer and NSCLC histology or sarcomatoid variant.

Other

• Spinal cord compression.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration.
• Life expectancy greater than or equal to (\>=) 12 weeks.
• Adequate organ and bone marrow function.
• Body weight greater than (\>) 35 kilograms (kg) at screening and at randomization.
• Histologically or cytologically documented NSQ NSCLC in substudy 1 and SQ or NSQ mNSCLC in substudy 2.
• Absence of sensitizing epidermal growth factor receptor (EGFR) mutations.
• Absence of documented tumor genomic alteration results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved targeted 1L therapies.
• At least one measurable lesion not previously irradiated that can be accurately measured at baseline as \>= 10 millimeter (mm) in the longest diameter.