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The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

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Category

Thoracic Cancer

PD-1 x VEGF Bispecific Antibody

PF-08634404 is an investigational compound. Its safety and efficacy have not been established.

AN INTERVENTIONAL PHASE 3, DOUBLE-BLIND, RANDOMIZED STUDY TO EVALUATE EFFICACY AND SAFETY OF PF-08634404 IN COMBINATION WITH CHEMOTHERAPY VERSUS PEMBROLIZUMAB IN COMBINATION WITH CHEMOTHERAPY IN ADULT PARTICIPANTS WITH LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER

Phase 3

NCT07222566

Active enrolling

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Locations

Global

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Study design
Participant Group/Arm

EXPERIMENTAL: Arm A

Participants will receive PF-08634404 combined with chemotherapy regimen 1, followed by maintenance therapy with PF-08634404.

Intervention/Treatment

BIOLOGICAL: PF-08634404

Solution for infusion

DRUG: Chemotherapy Regimen 1

Injection for IV use

Participant Group/Arm

ACTIVE_COMPARATOR: Arm B

Participants will receive pembrolizumab combined with chemotherapy regimen 1, followed by maintenance therapy with pembrolizumab.

Intervention/Treatment

BIOLOGICAL: Pembrolizumab

Injection for IV use

DRUG: Chemotherapy Regimen 1

Injection for IV use

Participant Group/Arm

EXPERIMENTAL: Arm C

Participants will receive PF-08634404 combined with chemotherapy regimen 2, followed by maintenance therapy with PF-08634404 and chemotherapy.

Intervention/Treatment

BIOLOGICAL: PF-08634404

Solution for infusion

DRUG: Chemotherapy Regimen 2

Injection for IV use

Participant Group/Arm

ACTIVE_COMPARATOR: Arm D

Participants will receive pembrolizumab combined with chemotherapy regimen 2, followed by maintenance therapy with pembrolizumab and chemotherapy.

Intervention/Treatment

BIOLOGICAL: Pembrolizumab

Injection for IV use

DRUG: Chemotherapy Regimen 2

Injection for IV use

Study design table for Clinical Trial
Key eligibility criteria
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 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 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.

Key dates
Study start date
  • December 2025
Estimated Study Completion Date
  • August 2032
Key endpoints
Primary Outcome Measures
Outcome Measure

Overall Survival

Measure Description

Overall survival defined as the time from the date of randomization to the date of death due to any cause.

Time Frame

Approximately 39 months

Outcome Measure

Progression Free Survival (PFS) assessed by blinded independent central review (BICR)

Measure Description

Progression-free survival is defined as the time from the date of randomization to the date of the first documentation of objective progressive disease (PD) assessed by BICR per RECIST v1.1, or death due to any cause, whichever occurs first.

Time Frame

Approximately 32 months

Primary Outcome Measures table for Clinical Trial
Secondary Outcome Measures:
Outcome Measure

Confirmed objective response rate (ORR) using RECIST v1.1 as assessed by BICR

Measure Description

ORR is defined as the proportion of participants in the analysis population having a best overall response (BOR) of confirmed CR or confirmed PR according to RECIST v1.1 as assessed by BICR.

Time Frame

Approximately 32 months

Outcome Measure

Progression Free Survival as assessed by Investigator

Measure Description

Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of the first documentation of objective PD assessed by investigator per RECIST v1.1, or death due to any cause, whichever occurs first.

Time Frame

Approximately 32 months

Outcome Measure

Confirmed ORR using RECIST v1.1 as assessed by investigator

Measure Description

ORR is defined as the proportion of participants in the analysis population having a BOR of confirmed CR or confirmed PR according to RECIST v1.1 as assessed by BICR.

Time Frame

Approximately 32 months

Outcome Measure

Duration of Response (DoR) as assessed by BICR

Measure Description

The time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of the first documentation of PD as determined by BICR assessment per RECIST v1.1, or death due to any cause, whichever occurs first.

Time Frame

Approximately 32 months

Outcome Measure

Duration of Response (DoR) as assessed by Investigator

Measure Description

The time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of the first documentation of PD as determined by investigator assessment per RECIST v1.1, or death due to any cause, whichever occurs first.

Time Frame

Approximately 32 months

Outcome Measure

Number of Participants With Adverse Events (AEs)

Measure Description

AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to study intervention(s).

Time Frame

Through end of study and up to approximately 39 months

Outcome Measure

Number of Participants With Clinical Laboratory Abnormalities

Measure Description

Laboratory test abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) and timing.

Time Frame

through end of study and up to approximately 39 months

Outcome Measure

Pharmacokinetics (PK): Serum concentrations of PF-08634404

Measure Description

Predose and postdose concentrations of PF-08634404

Time Frame

Through end of study and up to approximately 39 months

Outcome Measure

Incidence of Anti-Drug Antibody (ADA) against PF-08634404.

Measure Description

Time Frame

Through end of study and up to approximately 39 months

Outcome Measure

Mean scores and Change from baseline in the global health status/quality of life (QoL) score on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)

Measure Description

The EORTC QLQ-C30 is a questionnaire for quantitative measure of health-related quality of life pertinent to participants with a broad range of cancers who are participating in international clinical trials.

Time Frame

Approximately 39 months

Outcome Measure

Time to definitive deterioration (TTdD) in in the global health status/QoL score on the EORTC QLQ-C30

Measure Description

TTdD is defined as the time from date of randomization to first onset of Patient Reported Outcome (PRO) deterioration without subsequent recovery.

Time Frame

Approximately 39 months

Outcome Measure

Mean scores and Change from Baseline in dyspnea, cough, and chest pain scores on the EORTC Quality of Life Cancer Questionnaire - Lung Cancer 13 QLQ-LC13

Measure Description

EORTC QLQ-LC13 is a lung cancer specific module that serves as an additional 13 item questionnaire to the general EORTC cancer questionnaire, the EORTC QLQ-C30.

Time Frame

Approximately 39 months

Outcome Measure

TTdD in the dyspnea, cough, and chest pain scores on the EORTC QLQ-LC13

Measure Description

TTdD is defined as the time from date of randomization to first onset of Patient Reported Outcome (PRO) deterioration without subsequent recovery.

Time Frame

Approximately 39 months

Secondary Outcome Measures table for Clinical Trial
Number of participants

1500

Collaborators and investigators

Sponsor: Pfizer

Collaborator: None

This information is current as of October 30th 2025.

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More Information Close NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier. NCT07222566