A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Chemotherapy in Adult Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Participants with known actionable genomic alteration (AGAs), including estimated glomerular filtration rate (EGFR), anaplastic lymphoma kinase (ALK), Repressor of Silencing 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), rearranged during transfection (RET), and mesenchymal-epithelial transition (MET), for which there are available first-line therapies per local standard-of-care (SOC) are ineligible. Documented negative results for EGFR, ALK, and ROS1 AGAs are required for participants with non-squamous histology.

Known active CNS lesions are excluded. Participants with definitively treated brain metastases (surgery and/or radiotherapy) may be eligible. Clinically inactive brain metastases of longest diameter < 1 cm are permitted.

Participants with clinically significant risk of hemorrhage or fistula are excluded.

Participants with any history of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.

Unresolved toxicities from prior anti-tumor therapy, that did not recover to NCI CTCAE v5.0 Grade 0 or 1.

Known to have a history of a severe allergy to any component of the study intervention, or a history of severe allergic reaction to chimeric or humanized antibody.

History of allogeneic organ / hematopoietic stem cell transplantation.

Participants with any of the following respiratory conditions:

Evidence of noninfectious or drug-induced interstitial lung disease (ILD) or pneumonitis

Grade ≥3 pulmonary disease unrelated to underlying malignancy

History of uncontrolled comorbidities within 6 months prior to the first dose including uncontrolled cardiac and cerebrovascular conditions, hypertension, diabetes, significant vascular disease or arterial/severe venous thromboembolic events.

Major surgery < 4 weeks or minor surgery < 3 days prior to first dose of study intervention.

History of severe bleeding tendency or coagulation dysfunction

History of esophageal varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to the first dose.

Participants with acute, chronic or symptomatic infections including participants positive for active HIV, hepatitis B virus (HBV), or Hepatitis C virus (HCV).

Participants with history of immunodeficiency

Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior (in the past 5 years) or laboratory abnormality that may increase the risk of study participation or make the participant inappropriate for the study.

Previous systemic anti-tumor therapy including:

1. Prior systemic therapy, including anti-PD-(L)1 therapy, for locally advanced, unresectable, or metastatic NSCLC.
2. Previous treatment with immunotherapy
3. Prior radiotherapy > 30 Gy to the lung < 6 months of first dose of study intervention
4. Palliative local therapy < 2 weeks before the first dose of study intervention;
5. Non-specific immunomodulatory therapy < 2 weeks before the first dose.
6. Prior systemic anti-angiogenic therapy

Prior immune-related AE that led to anti-PD-(L)1 treatment discontinuation, adverse events from prior immunotherapy not improved to Grade 1 before screening, or required treatment with systemic immunosuppressive therapy.

Prior and concomitant therapy:

1. therapeutic oral or parenteral anticoagulants or thrombolytic agents < 10 days to the first dose.
2. chronic antiplatelet therapy <7 days to randomization.
3. live or attenuated live vaccine < 4 weeks to the first dose.
4. current high-dose systemic corticosteroids.
5. prohibited concomitant medication(s) < 21 days to the first dose.

Breastfeeding participants, participants of childbearing potential, and male participants who are unwilling to follow contraceptive measures.