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

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab, both in combination with platinum-based doublet chemotherapy, as a 1L treatment for patients with locally advanced or metastatic non-squamous NSCLC whose tumors express PD-L1 (TC ≥ 1%).

Inclusion criteria

• Histologically or cytologically documented non-squamous NSCLC.
• Stage III B/C or IV NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.
• Absence of sensitizing EGFR mutations (including, but not limited to, exon 19 deletion and exon 21 L858R, exon 21 L861Q, exon 18 G719X, and exon 20 S768I mutations) and ALK and ROS1 rearrangements.
• Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved and available 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 at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT or MRI and is 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 or anticonvulsants for at least 7 days prior to randomization. A minimum of 2 weeks must have elapsed between the end of local therapy (brain radiotherapy or surgery) and randomization. Participants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure) or surgery prior to randomization.
• Any prior systemic therapy received for NSCLC except in the neoadjuvant or adjuvant setting or definitive chemoradiotherapy with the intent to cure, provided that progression has occurred > 12 months after the end of systemic therapy treatment.
• Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting 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 curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence.
• Active or prior documented autoimmune or inflammatory disorders requiring chronic systemic treatment with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs.
• Active primary immunodeficiency/active infectious disease(s).
• Active tuberculosis infection.