The purpose of this study is to compare the clinical benefit of the combination of Navlimetostat (BMS-986504) (a selective MTA-cooperative inhibitor of PRMT5) plus pembrolizumab and chemotherapy versus placebo plus pembrolizumab and chemotherapy in first-line metastatic non-small cell lung cancer participants with homozygous MTAP deletion

Inclusion Criteria

• Participants must have Metastatic (Stage IV or recurrent) non-small cell lung cancer (NSCLC) (as defined by the American Joint Committee on Cancer, Ninth Edition) with no prior systemic anti-cancer therapy for metastatic disease.
• Participants must have histologically confirmed diagnosis of NSCLC and homozygous methylthioadenosine phosphorylase (MTAP) deletion or MTAP loss.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Participants must have at least 1 measurable lesion as per RECIST v1.1.

Exclusion Criteria

• Nonsquamous participants must not have documented targetable oncogenic mutation or actionable genetic alterations (AGAs) for which there is a standard of care (SoC) available as first-line (1L) therapy.
• Participants must not have symptomatic brain metastases or spinal cord compression.
• Participants must not have any prior systemic therapy (chemotherapy, immunotherapy, targeted therapy, or biological therapy) for metastatic non-small cell lung cancer (mNSCLC).

Note: One cycle of SoC treatment prior to randomization will be allowed for participants who require immediate treatment if clinically indicated.

• Participants must not have any known or suspected impairment of gastrointestinal function that may prohibit the ability to absorb or swallow an oral medication without chewing or crushing.
• Other protocol-defined Inclusion/Exclusion criteria apply.

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

See Plan Description

See Plan Description

The Phase 2 portion of this study will be blinded to sites, participants, investigators, and certain site-facing members of the Sponsor.

The Phase 3 portion of this study will be blinded to participants, investigators, and the Sponsor.