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A Study to Learn About the Study Medicine Called PF-08046054/SGN-PDL1V Versus Docetaxel in Adult Participants With Previously-Treated Programmed Cell Death Ligand 1 (PD-L1) Positive Non-Small-Cell Lung Cancer (NSCLC)

RecruitingPhase 3

PADL1NK-005: A Randomized, Phase 3, Open-Label Study to Evaluate PF-08046054/SGN-PDL1V Versus Docetaxel in Adult Participants With Previously-Treated Programmed Cell Death Ligand 1 (PD-L1) Positive Non-Small-Cell Lung Cancer (NSCLC)

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
Inclusion Criteria

* Histologically or cytologically confirmed diagnosis of NSCLC with locally advanced, unresectable Stage IIIB or IIIC not eligible for definitive chemoradiotherapy or metastatic (Stage IV: M1a, M1b, or M1c) disease per the American Joint Committee on Cancer (AJCC) Staging Manual, Version 8.0, and the Union for International Cancer Control (UICC) Staging System. Note: Participants with a neuroendocrine component or histology are not eligible.
* PD-L1 expression on ≥1% of tumor cells based on local immunohistochemistry (IHC) testing with an assay utilizing the anti-PD-L1 monoclonal antibody clones 22C3 or SP263.
* Participants who have NSCLC with known AGAs are permitted.
* Able to provide any of the following tumor tissues for biomarker analysis:

  * Archival specimen (preferably collected within 12 months after the last anticancer therapy) (see laboratory manual for details); or
  * De novo biopsy from a tumor lesion, if medically feasible.
* Participants must have received the following therapies and progressed during or relapsed after receiving their most recent prior therapy, or have been intolerant to their most recent therapy:

Participants with no known AGAs must fulfill 1 of the following conditions:

* Received a platinum-based combination therapy for the treatment of metastatic or recurrent disease, and unless contraindicated, a PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy).
* Experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting and received a PD-(L)1 monoclonal antibody at any time during the course of treatment.

Participants with known AGAs (eg, EGFR mutations, ALK translocations, or other relevant actionable mutations) must fulfill the following conditions:

* Must have received at least 1 relevant AGA-targeted therapy if locally available and, in the opinion of the investigator, additional AGA-targeted therapy is not in the best interest of the participant
* Received a platinum-based combination therapy for the treatment of metastatic or recurrent disease, or experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting.
* May have received PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy).

Exclusion Criteria

* History of another malignancy within 3 years before the first dose of PF-08046054, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 5-year overall survival \[OS\] ≥90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
* Any central nervous system (CNS) lesions, unless definitively treated with CNS-directed local therapy (surgery and/or radiotherapy). Participants with definitively treated brain metastases are eligible if they meet the following criteria:

  * The participant is on a stable dose of ≤10 mg/day of prednisone or equivalent for at least \>14 days prior to randomization (if requiring steroid treatment).
  * No clinical or radiographic progression in the CNS following CNS-directed definitive radiotherapy and/or surgery.
  * Time since CNS-directed treatment is ≥28 days prior to randomization.
* Participants with a history of leptomeningeal metastasis are excluded.
* Prior treatment with an anti-PD-L1 agent (where indicated per protocol) within 5 half-lives.
* Previous receipt of an MMAE-containing agent or prior docetaxel.

There are additional inclusion and exclusion criteria. The study center will determine if criteria for participations are met.

About the study

The purpose of this study is to understand if PF-08046054 alone works well compared to standard-of-care docetaxel alone in participants with non-small cell lung cancer (NSCLC) with PD-L1 expression greater than or equal to 1% and had cancer progression during or after treatment with PD-L1 or PD-1 inhibitors, platinum-based chemotherapy, and targeted treatment regimen(s) for participants with known actionable genomic alterations (AGAs). Participants in this study must have cancer that has spread through their body or can't be removed with surgery or treated with definitive radiation.

Participants will randomly (like a flip of the coin) be assigned to either the PF-08046054 treatment group or the docetaxel treatment group. Participants in the PF-08046054 treatment group will receive an IV infusion (injected directly into the veins) twice during each 21-day cycle. Participants in the docetaxel treatment group will receive an IV infusion once during each 21-day cycle. Study participation may be up to 5 years if the participant's NSCLC is responding to treatment. The study team will see how each participant is doing with the study treatment during regular visits at the clinic.

What is being tested

Sponsor: Pfizer · Participants: 680 · Started: Sep 29, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT07144280

Locations in the U.S.

AlabamaAlabama Oncology, Shelby, Alabaster
Alabama Oncology, Bessemer, Bessemer
Alabama Oncology, Brookwood, Birmingham
Alabama Oncology, Grandview Cancer Center, Birmingham
Alabama Oncology, Princeton, Birmingham
Alabama Oncology, St Vincent's Birmingham, Birmingham
Alabama Oncology, St Vincent's East, Birmingham
University of Alabama at Birmingham, Birmingham
University of Alabama at Birmingham, Birmingham
University of Alabama at Birmingham, IDS Pharmacy, Birmingham
Southern Cancer Center, Daphne
Southern Cancer Center, PC, Foley
AlaskaAlaska Oncology and Hematology, Anchorage
ArkansasHighlands Oncology Group, PA, Fayetteville
Highlands Oncology Group, PA, Rogers
Highlands Oncology Group, Springdale
Highlands Oncology Group, PA, Springdale
CaliforniaAlta Bates Summit Medical Center Comprehensive Cancer Center, Berkeley
John Muir Health Clinical Research Center, Concord
UC San Diego Medical Center - Encinitas, Encinitas
Providence Medical Foundation, Fullerton
Providence St. Jude Medical Center, Fullerton
UC San Diego Medical Center-La Jolla (Jacobs Medical Center/Thornton Pavilion, La Jolla
UC San Diego Moores Cancer Center, La Jolla
UCSD Koman Family Outpatient Pavilion, La Jolla
Roseville Medical Plaza Care Center, Roseville
Sutter Medical Center, Sacramento Infusion Center at Roseville, Roseville
Buhler Specialty Pavilion, Sacramento
Sutter Medical Center, Sacramento Infusion Center, Sacramento
UC San Diego McGrath Outpatient Pavilion - Hillcrest, San Diego
UC San Diego Medical Center - Hillcrest, San Diego
UCSD Medical Center - Rancho Bernardo, San Diego
UC San Diego Medical Center - Vista, Vista
John Muir Health Cancer Center, Walnut Creek
John Muir Health Clinical Research Center, Walnut Creek
John Muir Medical Center - Walnut Creek Campus, Walnut Creek
ColoradoRocky Mountain Cancer Centers LLP, Aurora
Rocky Mountain Cancer Centers LLP, Boulder
Rocky Mountain Cancer Centers LLP, Centennial
Rocky Mountain Cancer Centers LLP, Colorado Springs
Rocky Mountain Cancer Centers LLP, Colorado Springs
Rocky Mountain Cancer Centers LLP, Denver
Rocky Mountain Cancer Centers,LLP, Denver
Rocky Mountain Cancer Centers LLP, Englewood
Rocky Mountain Cancer Centers LLP, Lakewood
Rocky Mountain Cancer Centers LLP, Littleton
Rocky Mountain Cancer Centers LLP, Lone Tree
Rocky Mountain Cancer Centers LLP, Longmont
Rocky Mountain Cancer Centers LLP, Pueblo
Rocky Mountain Cancer Centers LLP, Thornton
DelawareMedical Oncology Hematology Consultants, PA, Newark
FloridaCancer Care Centers of Brevard, Inc., Palm Bay
Florida Cancer Affiliates - Panama City, Panama City
GeorgiaTennessee Oncology, PLLC - Dalton, Dalton
Tennessee Oncology, PLLC - Ringgold, Ringgold
IllinoisIllinois Cancer Specialists, Arlington Heights
Illinois CancerCare- Bloomington, Bloomington
Illinois Cancer Specialists, Chicago
Illinois CancerCare Galesburg, Galesburg
Accellacare of Duly, Lisle
Illinois CancerCare-Ottawa-Fox River Cancer Center, Ottawa
Illinois CancerCare- Pekin, Pekin
Illinois Cancer Care, Peoria
Illinois CancerCare-Peru - Valley Regional Cancer Center, Peru
Illinois CancerCare - Washington, Washington
KentuckyNorton Audubon Hospital, Louisville
Norton Brownsboro Hospital, Louisville
Norton Cancer Institute Downtown, Louisville
Norton Cancer Institute, Audubon Hospital Campus, Louisville
Norton Cancer Institute, Brownsboro Hospital Campus, Louisville
Norton Cancer Institute, Downtown, Louisville
Norton Hospital, Louisville
LouisianaMary Bird Perkins Cancer Center, Baton Rouge
MarylandMaryland Oncology Hematology, P.A., Annapolis
Maryland Oncology Hematology, P.A., Bethesda
Maryland Oncology Hematology, PA, Brandywine
Maryland Oncology Hematology, Columbia
Maryland Oncology Hematology P.A., Germantown
Maryland Oncology Hematology, P.A, Largo
Maryland Oncology Hematology PA, Rockville
Maryland Oncology Hematology, P.A., Silver Spring
MassachusettsUniversity of Massachusetts Worcester, Worcester
MinnesotaMinnesota Oncology Hematology, PA, Burnsville
Allina Health Cancer Institute - Mercy Hospital, Coon Rapids
Minnesota Oncology Hematology, PA, Coon Rapids
Minnesota Oncology Hematology, P.A., Edina
Minnesota Oncology Hematology PA, Maple Grove
Minnesota Oncology Hematology, P.A., Maplewood
Allina Health Cancer Institute - Abbott Northwestern Hospital, Minneapolis
Minnesota Oncology Hematology, P.A..., Minneapolis
Allina Health Cancer Institute - United Hospital, Saint Paul
Minnesota Oncology Hematology, PA, Woodbury
MississippiBaptist Cancer Center, Southaven
MissouriMissouri Cancer Associates, Columbia
MontanaIntermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana, Billings
Bozeman Health Deaconess Hospital, Bozeman
Bozeman Health Deaconess Hospital - Bozeman Health Cancer Center, Bozeman
Bozeman Health Deaconess Hospital - Bozeman Health Clinical Research, Bozeman
NebraskaNebraska Medicine-Bellevue Medical Center, Bellevue
Nebraska Medicine, Omaha
Nebraska Medicine - Village Pointe, Omaha
University Of Nebraska Medical Center, Omaha
NevadaRenown Health Medical Oncology, Reno
Renown Office of Clinical Research, Reno
Renown Regional Medical Center, Reno
New JerseyEssex Oncology of North Jersey, Belleville
New MexicoCHRISTUS St. Vincent Regional Cancer Center, Santa Fe
Christus St. Vincent Regional Medical Center, Santa Fe
New YorkMontefiore Medical Center - Montefiore Medical Park, The Bronx
White Plains Hospital, White Plains
OhioUniversity Hospitals Seidman Cancer Center at UH Avon Health Center, Avon
Oncology_Hematology Care Clinical Trials,LLC, Cincinnati
Oncology_Hematology Care Clinical Trials,LLC, Cincinnati
Oncology_Hematology Care Clinical Trials,LLC, Cincinnati
University Hospitals Cleveland Medical Center, Cleveland
Oncology_Hematology Care Clinical Trials,LLC, Fairfield
University Hospitals Seidman Cancer Center at UH Mentor Health Center, Mentor
UH Minoff Health Center at Chagrin Highlands, Orange
OregonOHSU Knight Cancer Institute, Beaverton, Beaverton
Oncology Associates of Oregon, P.C., Eugene
OHSU Knight Cancer Institute, Gresham, Gresham
OHSU Knight Cancer Institute, East Portland, Portland
OHSU Knight Cancer Institute, Northwest, Portland
OHSU Research Pharmacy Services, CHH2, Portland
Oregon Health and Science University, Portland
Oregon Health and Science University, CHH1, Portland
Oregon Health and Science University, CHH2, Portland
Providence Cancer Institute Franz Clinic, Portland
Providence Investigational Drug Service - Westside, Portland
Providence Oncology and Hematology Care -Westside, Portland
OHSU Knight Cancer Institute, Tualatin, Tualatin
PennsylvaniaAlliance Cancer Specialists, PC, Bensalem
Consultants in Medical Oncology and Hematology, P.C., Broomall
Alliance Cancer Specialists, PC, Doylestown
Alliance Cancer Specialists, PC, Horsham
Alliance Cancer Specialists, P.C., Langhorne
Alliance Cancer Specialists, PC, Media
Alliance Cancer Specialists, PC, Sellersville
Alliance Cancer Specialists, PC, Wynnewood
TennesseeBaptist Cancer Center, Bartlett
Tennessee Oncology, PLLC - Chattanooga Downtown, Chattanooga
Tennessee Oncology, PLLC - Chattanooga Med Park II, Chattanooga
Tennessee Oncology, PLLC - Chattanooga Memorial, Chattanooga
Tennessee Oncology, PLLC - Investigational Drug Services/Supply Storage, Chattanooga
Tennessee Oncology, PLLC - Cleveland, Cleveland
Baptist Cancer Center, Collierville
The West Clinic PC dba West Cancer Center, Germantown
Tennessee Cancer Specialists, Knoxville
Tennessee Cancer Specialists - Parkwest Location, Knoxville
Tennessee Oncology, PLLC - Lebanon, Lebanon
Baptist Cancer Center, Memphis
Baptist Clinical Research Institute, Memphis
Tennessee Oncology, PLLC - Mount Juliet, Mount Juliet
Tennessee Oncology, PLLC - Murfreesboro, Murfreesboro
SCRI Oncology Partners, Nashville
Tennessee Oncology, PLLC - Investigational Drug Services, Nashville
Tennessee Oncology, PLLC - Nashville Elliston Place Plaza Medical Oncology & Hematology Clinic, Nashville
Tennessee Oncology, PLLC - Nashville Saint Thomas West, Nashville
Tennessee Oncology, PLLC - Shelbyville, Shelbyville
Tennessee Oncology, PLLC - Smyrna, Smyrna
TexasTexas Oncology - West Texas, Abilene
Texas Oncology-Northeast Texas, Allen
Texas Oncology-West Texas, Amarillo
Texas Oncology - DFW, Arlington
Texas Oncology - DFW, Arlington
The Center for Cancer and Blood Disorders, Arlington
Texas Oncology - Central South (Renfert Way), Austin
Texas Oncology Central South, Austin
Texas Oncology- Central South., Austin
Texas Oncology- Central South., Austin
Texas Oncology - Gulf Coast, Beaumont
Texas Oncology - DFW, Bedford
The Center for Cancer and Blood Disorders, Burleson
The University of Texas, MD Anderson Cancer Center - Woodlands, Conroe
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
The Center for Cancer and Blood Disorders, Fort Worth
Texas Oncology - DFW, Grapevine
Texas Oncology- Central South, Harlingen
Texas Oncology - Gulf Coast, Houston
The University of Texas MD Anderson Cancer Center, Houston
The University of Texas MD Anderson Cancer Center Clinical Research Imaging, Houston
The University of Texas MD Anderson Cancer Center Diagnostic Imaging, Houston
The University of Texas, MD Anderson Cancer Center - West Houston, Houston
The University of Texas, MD Anderson Cancer Center- Interventional Radiology, Houston
University of Texas MD Anderson Cancer Center, Houston
Texas Oncology - Gulf Coast, Humble
US Oncology Investigational Product Center (IPC), Irving
US Oncology Investigational Products Center (IPC), Irving
US Oncology Investigational Products Center(IPC), Irving
The University of Texas, MD Anderson Cancer Center - League City, League City
Texas Oncology-Northeast Texas, Lewisville
Texas Oncology-Northeast Texas, Longview
Covenant Children's Hospital- Joe Arrington Cancer Research and Treatment Center, Lubbock
Texas Oncology -Central South, 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
Baylor Scott & White Health - Round Rock, Round Rock
Texas Oncology - Gulf Coast, Sugar Land
The University of Texas, MD Anderson Cancer Center - Sugar Land, Sugar Land
Texas Oncology - Gulf Coast, The Woodlands
Texas Oncology-Northeast Texas, Tyler
Texas Oncology- Central South, Waco
Texas Oncology-Central South, Waco
The Center for Cancer and Blood Disorders, Weatherford
Texas Oncology - Gulf Coast, Webster
Texas Oncology - Central South, Weslaco
Texas Oncology-West Texas, Wichita Falls
VirginiaOncology & Hematology Associates of Southwest Virginia,Inc.DBA Blue Ridge Cancer Care, Blacksburg
Oncology & Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer care| Emmett Medical & Surgical Center, Low Moor
VCU Emergency Center at New Kent, Quinton (Not yet recruiting)
Massey Cancer Center Clinical & Translational Research Lab, Richmond (Not yet recruiting)
VCU Health Short Pump Pavilion, Richmond (Not yet recruiting)
VCU Health Stony Point, Richmond (Not yet recruiting)
VCU Medical Center Gateway Building, Richmond (Not yet recruiting)
Virginia Commonwealth University, Richmond (Not yet recruiting)
Virginia Commonwealth University, Richmond (Not yet recruiting)
Oncology & Hematology Associates of Southwest Virginia, Inc.,DBA Blue Ridge Cancer Care, Roanoke
Oncology & Hematology Associates of Southwest Virginia Inc dba Blue Ridge Cancer Care, Salem
VCU Health Community Memorial Hospital, South Hill (Not yet recruiting)
VCU Health Tappahannock Hospital, Tappahannock (Not yet recruiting)
Shenandoah Oncology, P.C., Winchester
Oncology & Hematology Associates of Southwest Virginia, Inc.,DBA Blue Ridge Cancer Care, Wytheville
WashingtonAmerican Oncology Network Vista Oncology Division-East office, Olympia
American Oncology Network Vista Oncology Division-West office, Olympia

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.