• 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
• 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.
Key exclusion criteria
• 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.