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Symbiotic-Lung-01 : 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

RecruitingPhase 3

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

Who can join

Ages 18 and older · All sexes

Full 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.

About the study

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 with a type of lung cancer called non-small cell lung cancer (NSCLC) that is either locally advanced (spread to nearby tissues) or has spread to other parts of the body.

To join the study, participants must meet the following conditions:

* Be 18 years or older. * Have locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) squamous or non-squamous NSCLC. * Is not a candidate for complete surgical resection or curative chemoradiotherapy. * Do not have known actionable genomic alterations * Be treatment naïve for advanced or metastatic disease

Participants in this study will be assigned to two different parts of the study depending on their type of tumor: participants with squamous NSCLC will be assigned to Part 1, while participants with non-squamous NSCLC will be assigned to Part 2.

Each participant will be randomly assigned (like a flip of the coin) to one of two treatment groups in a blinded fashion:

* Part 1 - Arm A or Part 2 - Arm C (Experimental Group): Will receive a new study medicine called PF-08634404 along with a kind of chemotherapy specific to the type of tumor. * Part 1 - Arm B or Part 2 - Arm D (Control Group): Will receive an approved medicine called pembrolizumab along with a kind of chemotherapy specific to the type of tumor.

Participants will receive their assigned treatment through intravenous (IV) infusions, which means the medicine is given directly into a vein. The treatment will be given in cycles, participants will receive PF-08634404 or Pembrolizumab in combination with chemotherapy followed by maintenance with either PF-08634404 or Pembrolizumab monotherapy (Part 1) or PF-08634404 or Pembrolizumab in combination with a chemotherapeutic drug (Part 2). Participants will continue receiving treatment if it is helping and not experiencing serious side effects.

The study will include regular visits for:

* Treatment and health checks: while participant continues receiving treatment. * Tests to monitor how cancer responds: every 6 weeks during the first 48 weeks, then every 12 weeks thereafter.

What is being tested

Sponsor: Pfizer · Participants: 1,410 · Started: Jan 6, 2026

Contact the study team

Official record on ClinicalTrials.gov — NCT07222566

Locations in the U.S.

ArizonaPioneer Research Center, Bullhead City
Ironwood Cancer & Research Centers, Chandler
Ironwood Cancer & Research Centers, Gilbert
Ironwood Cancer & Research Centers, Glendale
Ironwood Cancer & Research Centers, Goodyear
Ironwood Cancer & Research Centers, Mesa
Ironwood Cancer & Research Centers, Mesa
Ironwood Cancer & Research Centers, Phoenix
Ironwood Cancer & Research Centers, Scottsdale
ArkansasHighlands Oncology Group, Fayetteville
Highlands Oncology Group, Rogers
Highlands Oncology Group, Springdale
CaliforniaOncura Health - Anaheim, Anaheim
Memorial Care Orange Coast Medical Center Attn, Fountain Valley
MemorialCare Orange Coast Medical Center, Fountain Valley
OC Blood and Cancer Care, Fountain Valley
Oncura Health - Fountain Valley, Fountain Valley
Oncura Health - Corporate (Central IDS & Regulatory Only), Glendale
Memorial Care Saddleback Medical Center Attn, Laguna Hills
MemorialCare Saddleback Medical Center, Laguna Hills
Stockton Hematology Oncology Medical Group, Lodi
Memorial Care Long Beach Medical Center, Long Beach
Cancer and Blood Research Center, LLC (Storage), Los Alamitos (Not yet recruiting)
Cancer and Blood Specialty Clinic, Los Alamitos (Not yet recruiting)
California Research Institute, Los Angeles
Oncura Health - Good Samaritan, Los Angeles
Stockton Hematology Oncology Medical Group, Manteca
Stockton Hematology Oncology Medical Group, Modesto
Oncura Health - Riverside, Riverside
Sansum Clinic, Santa Barbara
Sansum Clinic, Solvang
Stockton Hematology Oncology Group, Stockton
Cancer and Blood Specialty Clinic, Torrance (Not yet recruiting)
Stockton Hematology Oncology Medical Group, Tracy
Oncura Health - Valley Presbyterian, Van Nuys
FloridaFlorida Cancer Specialists, Bonita Springs
Florida Cancer Specialists, Bradenton
Florida Cancer Specialists, Cape Coral
Florida Cancer Specialists, Clearwater
Clermont Oncology Center, Clermont (Not yet recruiting)
BRCR Global- Coral Springs, Coral Springs
Florida Cancer Specialists, Daytona Beach
Cancer Specialists of North Florida, Fleming Island
Florida Cancer Specialists, Fleming Island
Helios Clinical Research, Fort Lauderdale
Florida Cancer Specialists, Fort Myers
Florida Cancer Specialists, Fort Myers
Florida Cancer Specialists - South, Fort Myers
Florida Cancer Specialists, Gainesville
Cancer Specialists of North Florida, Jacksonville
Cancer Specialists of North Florida, Jacksonville
Cancer Specialists of North Florida, Jacksonville
Cancer Specialists of North Florida, Jacksonville
Florida Cancer Specialists, Largo
Florida Cancer Specialists, Lecanto
Florida Cancer Specialists, N. Venice
Florida Cancer Specialists, Naples
Cancer Specialists of North Florida, Neptune Beach
Florida Cancer Specialists, Ocala
Alpha Clinical Research Centers LLC, Orange City
Florida Cancer Specialists, Orange City
Mid Florida Hematology and Oncology Center, Orange City
Florida Cancer Specialists, Orlando
Orlando Health Ambulatory Care Center, Orlando
Orlando Health Cancer Institute, Orlando
Orlando Health Orlando Regional Medical Center, Orlando
Cancer Care Centers of Brevard, Inc., Palm Bay
Florida Cancer Specialists, Palm Beach Gardens
Florida Cancer Specialists, Port Charlotte
Hematology Oncology Associates of the Treasure Coast, Port Saint Lucie
Cancer Specialists of North Florida, Saint Augustine
Florida Cancer Specialists, Sarasota
Florida Cancer Specialists, Sebring
Florida Cancer Specialists, St. Petersburg
Florida Cancer Specialists, St. Petersburg
Florida Cancer Specialists, Tallahassee
BRCR Medical Center Inc., Tamarac
Florida Cancer Specialists, Tampa
Florida Cancer Specialists, Tavares
Florida Cancer Specialists, The Villages
Florida Cancer Specialists, Trinity
Florida Cancer Specialists, Wellington
Florida Cancer Specialists - East, West Palm Beach
Florida Cancer Specialists, Winter Park
IllinoisIllinois CancerCare - Bloomington, Bloomington
Illinois Cancer Specialists, Chicago
University of Illinois Hospital and Health Sciences System, Chicago
University of Illinois Hospital and Health Sciences System (Outpatient Cancer Center), Chicago
Illinois CancerCare - Galesburg, Galesburg
Hope and Healing Cancer Services, Hinsdale
Hope and Healing Cancer Services, New Lenox
Illinois Cancer Specialists, Niles
Illinois CancerCare-Ottawa-Fox River Cancer Center, Ottawa
Illinois CancerCare-Pekin, Pekin
Illinois CancerCare, P.C., Peoria
Illinois CancerCare-Peru - Valley Regional Cancer Center, Peru
Illinois CancerCare-Washington, Washington
IndianaCommunity Health Network, Inc, Indianapolis
Community Health Network, Inc., Indianapolis
Community Health Network, Inc., Indianapolis
LouisianaPontchartrain Cancer Center, Covington
Pontchartrain Cancer Center, Hammond
MarylandMaryland Oncology Hematology, P.A., Annapolis
Maryland Oncology Hematology, P.A., Bethesda
Maryland Oncology Hematology, P.A., Brandywine
Maryland Oncology Hematology - Columbia, Columbia
Maryland Oncology Hematology, P.A., Germantown
Maryland Oncology Hematology, P.A., Largo
Maryland Oncology Hematology, P.A., Rockville
Maryland Oncology Hematology, P.A., Silver Spring
MinnesotaMinnesota Oncology Hematology, P.A., Burnsville
Minnesota Oncology Hematology, P.A., Chaska
Allina Health Cancer Institute - Mercy Hospital, Coon Rapids
Minnesota Oncology Hematology, P.A., Coon Rapids
Minnesota Oncology Hematology, P.A., Edina
Minnesota Oncology Hematology, P.A., Maple Grove
Minnesota Oncology Hematology, P.A., Maplewood
Allina Health Cancer Institute - Abbott Northwestern Hospital, Minneapolis
Allina Health Cancer Institute - United Hospital, Saint Paul
Minnesota Oncology Hematology, P.A., Woodbury
MississippiHattiesburg Clinic Hematology/Oncology, Hattiesburg
NebraskaCancer Partners of Nebraska, Lincoln
NHO Revive Research Institute, LLC, Lincoln
NHO Support Center, Lincoln
New MexicoUniversity of New Mexico Comprehensive Cancer Center, Albuquerque
CHRISTUS St. Vincent Regional Cancer Center, Santa Fe (Not yet recruiting)
New YorkNew York Oncology Hematology, Albany
New York Oncology Hematology, Clifton Park
Hematology Oncology Associates of Rockland, Nyack
North CarolinaFirstHealth Cancer Center, Pinehurst
FirstHealth Moore Regional Hospital, Pinehurst
Carolina Cancer Research Center, Wilson
OhioAultman Hospital, Canton
Aultman Medical Group Hematology and Oncology, Canton
Oncology Hematology Care Clinical Trials, Cincinnati
Oncology Hematology Care Clinical Trials, Cincinnati
Oncology Hematology Care Clinical Trials, Cincinnati
University Hospitals Cleveland Medical Center, Cleveland
Oncology Hematology Care Clinical Trials, Fairfield
Aultman Massillon, Massillon
Aultman North, North Canton
Aultman Orrville Hospital, Orrville
OregonNorthwest Cancer Specialists, P.C, Happy Valley
Northwest Cancer Specialists, P.C., Portland
Northwest Cancer Specialists, P.C, Tigard
TennesseeTennessee Oncology, PLLC - Chattanooga - Medical Park II, Chattanooga
Tennessee Oncology, PLLC - Chattanooga Downtown, Chattanooga
Tennessee Oncology, PLLC - Franklin, Franklin
Tennessee Oncology, PLLC - Gallatin, Gallatin
Tennessee Cancer Specialists - Parkwest Location, Knoxville
Tennessee Cancer Specialists Dowell Springs location, Knoxville
University of Tennessee Medical Center, Knoxville
Tennessee Oncology, PLLC - Lebanon, Lebanon
Tennesseee Oncology, PLLC - Mount Juliet, Mount Juliet
Tennessee Oncology, PLLC - Murfreesboro, Murfreesboro
SCRI Oncology Partners, Nashville
Tennessee Oncology, PLLC - Saint Thomas West, Nashville
Tennessee Oncology, PLLC-Elliston Place Plaza Medical Oncology &Hematology, Nashville
Tennessee Oncology, PLLC -Shelbyville, Shelbyville
TexasTexas Oncology - West Texas, Abilene
Texas Oncology - Northeast Texas, Allen
Texas Oncology - West Texas, Amarillo
Texas Oncology - DFW, Arlington
Texas Oncology - DFW, Arlington
Texas Oncology - Central/South Texas, Austin
Texas Oncology - Gulf Coast, Beaumont
Texas Oncology - DFW, Bedford
Texas Oncology - DFW, Dallas
Texas Oncology - DFW, Dallas
Texas Oncology - DFW, Dallas
Texas Oncology - DFW, Dallas
Texas Oncology - DFW, Dallas
Texas Oncology - Northeast Texas, Denison
Texas Oncology - Northeast Texas, Denton
Texas Oncology - West Texas, El Paso
Texas Oncology - West Texas, El Paso
Texas Oncology - West Texas, El Paso
Texas Oncology - Northeast Texas, Flower Mound
Texas Oncology - DFW, Fort Worth
Texas Oncology - DFW, Grapevine
Texas Oncology - Central/South Texas, Harlingen
Kelsey Research Foundation, Houston (Not yet recruiting)
Kelsey-Seybold Clinic - Berthelsen Main Campus, Houston (Not yet recruiting)
Kelsey-Seybold Clinic - Memorial Villages Campus, Houston (Not yet recruiting)
Kelsey-Seybold Clinic - North Houston Campus, Houston (Not yet recruiting)
Texas Oncology - Gulf Coast, Houston
Texas Oncology - Gulf Coast, Houston
Texas Oncology - Gulf Coast, Houston
Texas Oncology - Gulf Coast, Humble
US Oncology Investigational Products Center, Irving
US Oncology Investigational Products Center (IPC), Irving
Texas Oncology - Northeast Texas, Lewisville
Texas Oncology - Northeast Texas, Longview
Texas Oncology - Central/South Texas, McAllen
Texas Oncology - Northeast Texas, McKinney
Texas Oncology - West Texas, Midland
Texas Oncology - West Texas, Odessa
Texas Oncology - Northeast Texas, Palestine
Texas Oncology - Northeast Texas, Paris
Texas Oncology - Gulf Coast, Pearland
Texas Oncology - DFW, Plano
Texas Oncology - DFW, Plano
Kelsey-Seybold Clinic - Springwoods Village Campus, Spring (Not yet recruiting)
Kelsey-Seybold Clinic - Fort Bend Campus, Sugar Land (Not yet recruiting)
Texas Oncology - Gulf Coast, Sugar Land
Texas Oncology - Gulf Coast, The Woodlands
Texas Oncology - Northeast Texas, Tyler
Texas Oncology - Central/South Texas, Waco
Kelsey-Seybold Clinic - Bay Area Campus Building A, Webster (Not yet recruiting)
Kelsey-Seybold Clinic - Bay Area Campus Building B, Webster (Not yet recruiting)
Kelsey-Seybold Clinic - Bay Area Campus Building C, Webster (Not yet recruiting)
Texas Oncology - Gulf Coast, Webster
Texas Oncology - Central/South Texas, Weslaco
Texas Oncology - West Texas, Wichita Falls
UtahHuntsman Cancer Institute, University of Utah, Salt Lake City
VirginiaUVA Comprehensive Cancer Center, Charlottesville
UVA Health Cancer Care Pantops, Charlottesville
UVA Health Fontaine Research Park, Charlottesville
University of Virginia, Charlottesville
WashingtonNorthwest Cancer Specialists, P.C., Vancouver
WisconsinMinnesota Oncology Hematology, P.A., Hudson
Froedtert Hospital/Medical College of Wisconsin, Milwaukee

Conditions

From ClinicalTrials.gov, data retrieved Sep 29, 2026. Each study sets its own eligibility; the study team decides who can join.