A global study of volrustomig (MEDI5752) plus chemotherapy versus pembrolizumab plus chemotherapy for participants with metastatic non-small cell lung cancer.

Prior treatment

• No prior exposure to immunotherapy.
• 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 whole brain radiotherapy and study enrollment.
• History of another primary malignancy except for: (a) 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. (b) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. (c) Adequately treated carcinoma in situ without evidence of disease.

Other illness

• Mixed small-cell lung cancer and NSCLC histology or sarcomatoid variant. Rare subtypes (eg, NUT carcinoma, thoracic SMARCA4-deficient undifferentiated tumor, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma) are excluded.
• As judged by the investigator, any condition that would interfere with evaluation of the study intervention or interpretation of participant safety or study results.

Other

• No medical contraindication to platinum-based treatment.
• Spinal cord compression.

• Histologically or cytologically documented squamous or non-squamous NSCLC. Stage IV NSCLC (according to Version 8 of the IASLC Staging
• Provision of tumor sample for prospective PD-L1 testing .
• PD-L1 <50%.
• Absence of sensitizing EGFR mutations (including, but not limited to, exon 19 deletion or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation) 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 (eg, NTRK, BRAF, RET, MET, etc.) for which there are locally approved targeted first-line therapies.