Status:

NOT_YET_RECRUITING

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

Lead Sponsor:

Pfizer

Conditions:

Advanced Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer

Eligibility:

All Genders

18+ years

Phase:

PHASE3

Brief Summary

This study is being done to find out if a new medicine called PF-08634404, when given with chemotherapy, works better than the present standard treatment (pembrolizumab with chemotherapy) for adults w...

Eligibility Criteria

Inclusion

  • 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 complete surgical resection and curative concurrent/sequential chemoradiotherapy (according to the 9th edition of the Union for International Cancer Control and American Joint Committee on Cancer lung cancer Tumor, lymph nodes, metastasis (TNM) staging system).
  • Have tumor tissue available, either paraffin block or slides from a core, excisional or 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

  • 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:
  • Prior systemic therapy, including anti-PD-(L)1 therapy, for locally advanced, unresectable, or metastatic NSCLC.
  • Previous treatment with immunotherapy
  • Prior radiotherapy \> 30 Gy to the lung \< 6 months of first dose of study intervention
  • Palliative local therapy \< 2 weeks before the first dose of study intervention;
  • Non-specific immunomodulatory therapy \< 2 weeks before the first dose.
  • 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:
  • therapeutic oral or parenteral anticoagulants or thrombolytic agents \< 10 days to the first dose.
  • chronic antiplatelet therapy \<7 days to randomization.
  • live or attenuated live vaccine \< 4 weeks to the first dose.
  • current high-dose systemic corticosteroids.
  • 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.

Key Trial Info

Start Date :

December 5 2025

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

August 26 2032

Estimated Enrollment :

1500 Patients enrolled

Trial Details

Trial ID

NCT07222566

Start Date

December 5 2025

End Date

August 26 2032

Last Update

October 30 2025

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