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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-03-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2025-523461-17-01

ClinicalTrials.gov

NCT07222566

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Pharmacodynamic, Safety, Efficacy

To demonstrate that PF-08634404 + chemotherapy (experimental arm) is superior to pembrolizumab + chemotherapy (control arm) in prolonging OS.
To demonstrate that PF-08634404 + chemotherapy (experimental arm) is superior to pembrolizumab + chemotherapy (control arm) in prolonging PFS by BICR.

Secondary objectives 6

1. 1. Key - To compare ORR by BICR between experimental and control arms
2. 2. To evaluate additional measures of efficacy for the experimental and control arms
3. 3. To characterize the overall safety profile and tolerability of both treatment arms
4. 4. To evaluate the PK of PF-08634404 when administered in combination with chemotherapy
5. 5. To evaluate the immunogenicity of PF-08634404 when administered in combination with chemotherapy
6. 6. To evaluate PROs for each treatment arm

Conditions and MedDRA coding

LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 18 years of age or older
2. 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).
3. Have tumor tissue available, either paraffin block or slides from a core, excisional or fine needle biopsy
4. PD-L1 status available based on local testing results
5. Measurable disease based on RECIST v1.1 per investigator.
6. ECOG PS score of 0 or 1
7. Expected survival ≥12 weeks

Exclusion criteria 19

1. 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.
2. 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.
3. Participants with clinically significant risk of hemorrhage or fistula are excluded.
4. 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.
5. Unresolved toxicities from prior anti-tumor therapy, that did not recover to NCI CTCAE v5.0 Grade 0 or 1.
6. 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.
7. History of allogeneic organ / hematopoietic stem cell transplantation.
8. 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.
9. 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.
10. Major surgery < 4 weeks or minor surgery < 3 days prior to first dose of study intervention.
11. History of severe bleeding tendency or coagulation dysfunction
12. 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.
13. Participants with acute, chronic or symptomatic infections including participants positive for active HIV, HBV, or HCV.
14. Participants with history of immunodeficiency
15. 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.
16. 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.
17. 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.
18. 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.
19. Breastfeeding participants, participants of childbearing potential, and male participants who are unwilling to follow contraceptive measures.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall survival
2. PFS using RECIST v1.1 as assessed by BICR

Secondary endpoints 6

1. 1. Key - Confirmed ORR using RECIST v1.1 as assessed by BICR
2. 2. PFS using RECIST v1.1 as assessed by investigator; Confirmed ORR using RECIST v1.1 as assessed by investigator; DoR using RECIST v1.1 as assessed by BICR; DoR using RECIST v1.1 as assessed by investigator
3. 3. AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to study intervention(s); Laboratory test abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) and timing.
4. 4. Predose and postdose concentrations of PF-08634404.
5. 5. Incidence of ADA against PF-08634404
6. 6. Change from baseline in the global health status/QoL, and Physical function scores on the EORTC QLQ-C30; Change from baseline in dyspnea, cough, and chest pain scores on the EORTC QLQ-LC13; Time to definitive deterioration in the global health status/QoL and physical function scores on the EORTC QLQ-C30; Time to definitive deterioration in dyspnea, cough, and chest pain scores on the EORTC QLQ-LC13

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 5

Locations

8 EU/EEA countries · 93 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 105 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications