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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
- PF-08634404 (biological)
- Pembrolizumab (biological)
- Chemotherapy Regimen 1 (drug)
- Chemotherapy Regimen 2 (drug)
Sponsor: Pfizer · Participants: 1,410 · Started: Jan 6, 2026
Contact the study team
Official record on ClinicalTrials.gov — NCT07222566
Locations in the U.S.
| Arizona | Pioneer 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 |
| Arkansas | Highlands Oncology Group, Fayetteville Highlands Oncology Group, Rogers Highlands Oncology Group, Springdale |
| California | Oncura 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 |
| Florida | Florida 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 |
| Illinois | Illinois 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 |
| Indiana | Community Health Network, Inc, Indianapolis Community Health Network, Inc., Indianapolis Community Health Network, Inc., Indianapolis |
| Louisiana | Pontchartrain Cancer Center, Covington Pontchartrain Cancer Center, Hammond |
| Maryland | Maryland 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 |
| Minnesota | Minnesota 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 |
| Mississippi | Hattiesburg Clinic Hematology/Oncology, Hattiesburg |
| Nebraska | Cancer Partners of Nebraska, Lincoln NHO Revive Research Institute, LLC, Lincoln NHO Support Center, Lincoln |
| New Mexico | University of New Mexico Comprehensive Cancer Center, Albuquerque CHRISTUS St. Vincent Regional Cancer Center, Santa Fe (Not yet recruiting) |
| New York | New York Oncology Hematology, Albany New York Oncology Hematology, Clifton Park Hematology Oncology Associates of Rockland, Nyack |
| North Carolina | FirstHealth Cancer Center, Pinehurst FirstHealth Moore Regional Hospital, Pinehurst Carolina Cancer Research Center, Wilson |
| Ohio | Aultman 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 |
| Oregon | Northwest Cancer Specialists, P.C, Happy Valley Northwest Cancer Specialists, P.C., Portland Northwest Cancer Specialists, P.C, Tigard |
| Tennessee | Tennessee 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 |
| Texas | Texas 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 |
| Utah | Huntsman Cancer Institute, University of Utah, Salt Lake City |
| Virginia | UVA Comprehensive Cancer Center, Charlottesville UVA Health Cancer Care Pantops, Charlottesville UVA Health Fontaine Research Park, Charlottesville University of Virginia, Charlottesville |
| Washington | Northwest Cancer Specialists, P.C., Vancouver |
| Wisconsin | Minnesota 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.