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

Exclusion Criteria

• •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.