A Global Phase III Study of Rilvegostomig or Pembrolizumab Plus Chemotherapy for First-Line Treatment of Metastatic Non-squamous NSCLC

Inclusion Criteria:

• Histologically or cytologically documented non-squamous NSCLC.

• Stage IV mNSCLC (based on the American Joint Committee on Cancer Edition 8) notamenable to curative treatment.

• Absence of sensitizing EGFR mutations (including, but not limited to, exon 19deletion and exon 21 L858R, exon 21 L861Q, exon 18 G719X, and exon 20 S768Imutations) and ALK and ROS1 rearrangements.

• Absence of documented tumor genomic mutation results from tests conducted as part ofstandard local practice in any other actionable driver oncogenes for which there arelocally approved targeted 1L therapies.

• Provision of acceptable tumor sample, to confirm tumor PD-L1 expression TC ≥ 1%.

• At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL atbaseline and can be accurately measured at baseline as ≥ 10 mm in the longestdiameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT or MRI andis suitable for accurate repeated measurements.

• Adequate organ and bone marrow function

Exclusion Criteria:

• Presence of small cell and neuroendocrine histology components.

• Brain metastases unless asymptomatic, stable, and not requiring steroids oranticonvulsants for at least 7 days prior to randomization. A minimum of 2 weeksmust have elapsed between the end of local therapy (brain radiotherapy or surgery)and randomization. Participants must have recovered from the acute toxic effect ofradiotherapy (eg, dizziness and signs of increased intracranial pressure) or surgeryprior to randomization.

• Any prior systemic therapy received for advanced or mNSCLC. Prior systemic therapyin the neoadjuvant or adjuvant setting and/or definitive radio- or chemoradiotherapyfor early-stage disease are allowed, provided that recurrence or progression hasoccurred > 12 months after the end of treatment.

• Any prior exposure to an anti-TIGIT therapy or any other anticancer therapytargeting immune-regulatory receptors or mechanisms.

• Any prior treatment with an anti-PD-1 or anti-PD-L1 agent.

• History of another primary malignancy except for malignancy treated with curativeintent with no known active disease ≥ 2 years before the first dose of studyintervention and of low potential risk for recurrence.

• Active or prior documented autoimmune or inflammatory disorders requiring chronictreatment with steroids or other immunosuppressive treatment.

• Active primary immunodeficiency/active infectious disease(s).

• Active tuberculosis infection.