Efficacy and Safety of PF-08634404 Plus Combination Therapy Versus Pembrolizumab Plus Combination Therapy in Adults With Locally Advanced or Metastatic Non-Small Cell Lung Cancer
- Trial ID
- 2025-523461-17-01
- Protocol
- C6461001
- Sponsor
- Pfizer Inc.
Trial statistics
Objectives
The primary objective of this study is to evaluate the efficacy of PF-08634404 in combination with chemotherapy compared to pembrolizumab in combination with chemotherapy in participants with locally advanced or metastatic non-small cell lung cancer. Clinical relevance is established by demonstrating superiority in prolonging overall survival and progression-free survival as assessed by blinded independent central review.
The secondary objectives include:
- Comparison of objective response rate by blinded independent central review.
- Evaluation of additional efficacy measures.
- Characterization of the overall safety profile and tolerability.
- Assessment of the pharmacokinetics of PF-08634404 in combination with chemotherapy.
- Evaluation of the immunogenicity of PF-08634404.
- Assessment of patient-reported outcomes.
Participants
The study includes 1,023 participants diagnosed with locally advanced or metastatic non-small cell lung cancer. The population consists of both male and female patients within specific age ranges. Eligible participants must have pathologically confirmed squamous or non-squamous disease classified as Stage IIIB/IIIC or Stage IV according to the AJCC Staging Manual and the UICC Staging System. Selection is contingent upon the availability of tumor tissue and PD-L1 status. Participants must demonstrate measurable disease based on RECIST v1.1 and possess an ECOG performance status of 0 or 1. An expected overall survival of at least 12 weeks is required for inclusion.
Plans and Procedures
This is an interventional, Phase 3, double-blind, randomized study designed to evaluate the efficacy and safety of PF-08634404 in combination with chemotherapy compared to pembrolizumab in combination with chemotherapy. The study focuses on adult participants diagnosed with non-small cell lung cancer that is locally advanced or metastatic. The primary objectives are to demonstrate superiority in overall survival and progression-free survival as assessed by blinded independent central review. The experimental arm involves the administration of PF-08634404 alongside chemotherapy agents such as pemetrexed, carboplatin, paclitaxel, or paclitaxel albumin-bound via intravenous infusion. The control arm utilizes pembrolizumab in combination with chemotherapy. Secondary endpoints include objective response rate, duration of response, incidence of adverse events, and changes in quality of life. The study is estimated to occur between April 2026 and August 2032.
Treatment
PF-08634404 is administered as a concentrate for solution for infusion via the intravenous route at a dosage of 000 mg/kg.
Pemetrexed is administered via intravenous injection at a dosage of 000 mg/m2.
Carboplatin is administered via intravenous use at a dosage of 000 mg.
Paclitaxel is administered via intravenous injection at a dosage of 000 mg/m2.
Paclitaxel albumin-bound is administered via the intravenous route at a dosage of 000 mg/m2.
Pembrolizumab is administered via intravenous injection at a dosage of 000 mg.
Sodium chloride is utilized as a placebo and is administered via intravenous route at a dosage of 000 ml.
Efficacy
The assessment of efficacy in this study of non-small cell lung cancer involves several predefined parameters. The primary endpoints are overall survival and progression-free survival (PFS) evaluated via RECIST v1.1 as assessed by blinded independent central review (BICR).
Secondary efficacy parameters include:
- Confirmed objective response rate (ORR) as assessed by BICR.
- PFS and ORR as assessed by the investigator.
- duration of response (DoR) as assessed by both BICR and the investigator.
- Changes in quality of life (QoL) and physical function scores using the EORTC QLQ-C30.
- Changes in dyspnea, cough, and chest pain scores using the EORTC QLQ-LC13.
- Time to definitive deterioration in global health status, physical function, dyspnea, cough, and chest pain scores.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 18 years of age or older
- 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 chemoradiation per the AJCC Staging Manual and the UICC Staging System (Eighth edition).
- 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.
- ECOG PS score of 0 or 1
- Expected survival ≥12 weeks
Exclusion Criteria
- Participants with known AGAs, including EGFR, ALK, ROS1, NTRK, BRAF, RET, and MET, for which there are approved first-line therapies per local 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 ILD or pneumonitis -Known DLCO (adjusted for hemoglobin) <50% predicted. -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 and 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, HBV, or 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. a) (Neo)adjuvant anti-PD-(L)1 is allowed if recurrence or progression occurred ≥9 months after the last dose. b) Other (neo)adjuvant or definitive therapy is allowed if recurrence or progression occurred ≥6 months after the last dose. -Previous treatment with immunotherapy. -Prior radiotherapy to the lung < 6 months of first dose of study intervention. -Palliative local therapy < 2 weeks before the first dose. -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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Recruiting | 27 Apr 2026 | 24 |
 France | Recruiting | 27 Apr 2026 | 59 |
 Germany | Recruiting | 27 Apr 2026 | 42 |
 Greece | Recruiting | 27 Apr 2026 | 30 |
 Hungary | Recruiting | 27 Apr 2026 | 37 |
 Italy | Recruiting | 27 Apr 2026 | 28 |
 Poland | Not Yet Recruiting | 27 Apr 2026 | 47 |
 Spain | Recruiting | 27 Apr 2026 | 120 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PACLITAXEL | Test | — | INTRAVENOUS | 000 | 1 | SUB09583MIG |
PF-08634404 | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 000 | 1 | PRD12922792 |
SODIUM CHLORIDE | Placebo | — | INTRAVENOUS | 000 | 1 | SUB12581MIG |
PACLITAXEL ALBUMIN-BOUND | Test | — | INTRAVENOUS | 000 | 1 | SUB127678 |
PEMBROLIZUMAB | Test | — | INTRAVENOUS | 000 | 1 | SUB167136 |
CARBOPLATIN | Test | — | INTRAVENOUS USE | 000 | 1 | SUB06614MIG |
PEMETREXED | Test | — | INTRAVENOUS | 000 | 1 | SUB09655MIG |