The purpose of this study is to investigate the efficacy, safety, and immunogenicity of GME751 compared with Keytruda® (pembrolizumab) in participants with untreated metastatic non-squamous NSCLC (irrespective of PD-L1 status), without sensitizing EGFR or ALK mutations.

Eligible participants will be randomized in a 1:1 ratio to receive either GME751, or European Union (EU)-authorized pembrolizumab (Keytruda-EU) in combination with chemotherapy. The maximum study duration for a participant will be approximately 56 weeks including screening.

Treatment duration is 52 weeks (17 treatment cycles of study treatment GME751 or Keytruda-EU in combination with chemotherapy, each cycle with a duration of 3 weeks).

Participants will discontinue study participation in case of disease progression, unacceptable toxicity or other reasons.

Participants who are benefiting from treatment with pembrolizumab without signs of progression or unacceptable toxicity will be eligible for continued pembrolizumab treatment via most suitable option based on the respective country regulations.

Inclusion Criteria:

• At least 18 years of age
• Untreated metastatic NSCLC
• Absence of tumor activating EGFR mutations and absence of ALK gene rearrangements
• Measurable disease according to RECIST 1.1
• Adequate organ function
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

Exclusion Criteria:

• Squamous cell or mixed histology in NSCLC
• Known history of hypersensitivity (grade ≥3) to pembrolizumab, chemotherapy or their excipients
• Active autoimmune disease that has required chronic systemic treatment in the past 2 years.
• Received live vaccine ≤30 days before the first study treatment
• Prior treatment with pembrolizumab or any other anti-PD-1, or anti-PD-L1 or anti-PD-L2, or anti-CTLA-4 agent or any antibody targeting other immune-regulatory receptors or mechanisms for lung cancer.

Other protocol-defined inclusion/exclusion criteria apply.