• Open Label
• Randomized

• Experimental: Arm 1
Volrustomig plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion
• Active Comparator: Arm 2
Pembrolizumab plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion

• Progression-Free Survival (PFS)
• Overall Survival (OS), in PD-L1-negative participants

• Histologically or cytologically documented squamous or non-squamous NSCLC.
• Stage IV NSCLC (according to Version 8 of the IASLC Staging Manual in Thoracic Oncology 2016), not amenable to curative surgery or radiation.
• Absence of sensitizing EGFR mutations and ALK and ROS1 rearrangements.
• 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 first-line therapies.

• Mixed small-cell lung cancer and NSCLC histology or sarcomatoid variant. Rare subtypes are excluded.
• Spinal cord compression.
• Symptomatic brain metastases. Brain metastases may be treated or untreated, but participants must be asymptomatic and off steroids for at least 14 days prior to start of study intervention. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.
• History of another primary malignancy except for:
1. Malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence.
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
3. Adequately treated carcinoma in situ without evidence of disease.
• As judged by the investigator, any condition that would interfere with evaluation of the study intervention or interpretation of participant safety or study results.