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

Inclusion Criteria:

• 18 years of age or older at screening.

• Have pathologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV)squamous or non-squamous NSCLC and not be a candidate for completesurgical resection and curative concurrent/sequential chemoradiotherapy (accordingto the 9th edition of the Union for International Cancer Control and American JointCommittee on Cancer lung cancer Tumor, lymph nodes, metastasis (TNM) stagingsystem).

• Have tumor tissue available, either paraffin block or slides from a core, excisionalor fine needle biopsy

• PD-L1 status available based on local testing results

• Measurable disease based on RECIST v1.1 per investigator.

• Eastern Cooperative Oncology Group performance status (ECOG) score of 0 or 1

• Expected survival ≥12 weeks

Exclusion Criteria:

• Participants with known actionable genomic alteration (AGAs), including estimatedglomerular filtration rate (EGFR), anaplastic lymphoma kinase (ALK), Repressor ofSilencing 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), v-raf murinesarcoma viral oncogene homolog B1 (BRAF), rearranged during transfection (RET), andmesenchymal-epithelial transition (MET), for which there are available first-linetherapies per local standard-of-care (SOC) are ineligible. Documented negativeresults for EGFR, ALK, and ROS1 AGAs are required for participants with non-squamoushistology.

• Known active CNS lesions are excluded. Participants with definitively treated brainmetastases (surgery and/or radiotherapy) may be eligible. Clinically inactive brainmetastases 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 firstdose of study intervention, or any evidence of residual disease from a previouslydiagnosed malignancy.

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

• Known to have a history of a severe allergy to any component of the studyintervention, or a history of severe allergic reaction to chimeric or humanizedantibody.

• 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) orpneumonitis

• Grade ≥3 pulmonary disease unrelated to underlying malignancy

• History of uncontrolled comorbidities within 6 months prior to the first doseincluding uncontrolled cardiac and cerebrovascular conditions, hypertension,diabetes, significant vascular disease or arterial/severe venous thromboembolicevents.

• Major surgery < 4 weeks or minor surgery < 3 days prior to first dose of studyintervention.

• History of severe bleeding tendency or coagulation dysfunction

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

• Participants with acute, chronic or symptomatic infections including participantspositive 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) oractive suicidal ideation/behavior (in the past 5 years) or laboratory abnormalitythat may increase the risk of study participation or make the participantinappropriate 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 studyintervention

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, adverseevents from prior immunotherapy not improved to Grade 1 before screening, orrequired treatment with systemic immunosuppressive therapy.

• Prior and concomitant therapy:

1. therapeutic oral or parenteral anticoagulants or thrombolytic agents < 10 daysto 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 maleparticipants who are unwilling to follow contraceptive measures.