RecruitingInterventionalPhase 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)

NCT ID: NCT07144280Sponsor: PfizerLast updated: 2026-04-21

Summary

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.

Arms & interventions

DrugPF-08046054
Antibody Drug Conjugate Participants will receive PF-08046054, administered as an IV infusion.
DrugDocetaxel monotherapy
Participants will receive Docetaxel, administered as an IV infusion.

Outcome measures

Primary

Overall Survival
Overall survival defined as the time from the date of randomization to the date of death due to any cause.
Time frame: Approximately 5 years

Secondary

Progression Free Survival (PFS) assessed by blinded independent central review (BICR)
Time frame: Approximately 5 years
Objective Response Rate as assessed by BICR
Time frame: Approximately 5 years
Progression Free Survival as assessed by Investigator
Time frame: Approximately 5 years
Objective Response Rate (ORR) as assessed by Investigator
Time frame: Approximately 5 years
Duration of Response as assessed by BICR
Time frame: Approximately 5 years
Duration of Response as assessed by Investigator
Time frame: Approximately 5 years
Incidence of Treatment Emergent Adverse Events (TEAEs) estimated during the Adverse Events (AE) evaluation
Time frame: Through 90 days after the last study intervention; Approximately 5 years
Mean scores and Change from baseline in the global health status/quality of life (QoL) score on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
Time frame: Approximately 5 years
Mean scores and Change from baseline in physical functioning and role functioning scores on the EORTC QLQ-C30
Time frame: Approximately 5 years
Mean scores and Change from Baseline in dyspnea, cough, and chest pain scores on the EORTC Quality of Life Cancer Questionnaire - Lung Cancer 13 QLQ-LC13
Time frame: Approximately 5 years
Time to definitive deterioration (TTdD) in in the global health status/QoL score on the EORTC QLQ-C30
Time frame: Approximately 5 years
TTdD in physical functioning and role functioning scores on the EORTC QLQ-C30
Time frame: Approximately 5 years
TTdD in the dyspnea, cough, and chest pain scores on the EORTC QLQ-LC13
Time frame: Approximately 5 years
Pharmacokinetics (PK): Plasma concentration of PF-08046054 and and its components
Time frame: Approximately 48 weeks
Incidence of Anti-Drug Antibody (ADA)
Time frame: Approximately 48 weeks

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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.

Study locations (133)

Alabama Oncology

Alabaster, Alabama, 35007

Recruiting

Alabama Oncology

Bessemer, Alabama, 35022

Recruiting

Alabama Oncology, Bruno Cancer Center

Birmingham, Alabama, 35205

Recruiting

Alabama Oncology

Birmingham, Alabama, 35209

Recruiting

Alabama Oncology

Birmingham, Alabama, 35211

Recruiting

Alabama Oncology

Birmingham, Alabama, 35235

Recruiting

Alabama Oncology

Birmingham, Alabama, 35243

Recruiting

Southern Cancer Center

Daphne, Alabama, 36526

Recruiting

Southern Cancer Center, PC

Foley, Alabama, 36535

Recruiting

Alaska Oncology and Hematology

Anchorage, Alaska, 99508

Recruiting

Highlands Oncology Group, PA

Fayetteville, Arkansas, 72703

Not Yet Recruiting

Highlands Oncology Group, PA

Rogers, Arkansas, 72758

Not Yet Recruiting

Highlands Oncology Group, PA

Springdale, Arkansas, 72762

Not Yet Recruiting

Highlands Oncology Group

Springdale, Arkansas, 72762

Not Yet Recruiting

Providence Medical Foundation

Fullerton, California, 92835

Not Yet Recruiting

Providence St. Jude Medical Center

Fullerton, California, 92835

Not Yet Recruiting

Rocky Mountain Cancer Centers,LLP

Denver, Colorado, 80218

Recruiting

Medical Oncology Hematology Consultants, PA

Newark, Delaware, 19713

Not Yet Recruiting

Cancer Care Centers of Brevard, Inc.

Palm Bay, Florida, 32901

Recruiting

Florida Cancer Affiliates - Panama City

Panama City, Florida, 32405

Recruiting

Tennessee Oncology, PLLC - Dalton

Dalton, Georgia, 30720

Not Yet Recruiting

Tennessee Oncology, PLLC - Ringgold

Ringgold, Georgia, 30736

Not Yet Recruiting

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005

Not Yet Recruiting

Illinois CancerCare- Bloomington

Bloomington, Illinois, 61704

Recruiting

Illinois Cancer Specialists

Chicago, Illinois, 60631

Not Yet Recruiting

Illinois CancerCare Galesburg

Galesburg, Illinois, 61401

Recruiting

Accellacare of Duly

Lisle, Illinois, 60532

Recruiting

Illinois CancerCare-Ottawa-Fox River Cancer Center

Ottawa, Illinois, 61350

Recruiting

Illinois CancerCare- Pekin

Pekin, Illinois, 61554

Recruiting

Illinois Cancer Care

Peoria, Illinois, 61615

Recruiting

Illinois CancerCare-Peru - Valley Regional Cancer Center

Peru, Illinois, 61354

Recruiting

Illinois CancerCare - Washington

Washington, Illinois, 61571

Recruiting

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809

Not Yet Recruiting

Maryland Oncology Hematology, P.A.

Annapolis, Maryland, 21401

Not Yet Recruiting

Maryland Oncology Hematology, P.A.

Bethesda, Maryland, 20817

Not Yet Recruiting

Maryland Oncology Hematology, PA

Brandywine, Maryland, 20613

Not Yet Recruiting

Maryland Oncology Hematology

Columbia, Maryland, 21044

Not Yet Recruiting

Maryland Oncology Hematology P.A.

Germantown, Maryland, 20876

Not Yet Recruiting

Maryland Oncology Hematology, P.A

Largo, Maryland, 20774

Not Yet Recruiting

Maryland Oncology Hematology PA

Rockville, Maryland, 20850

Not Yet Recruiting

Maryland Oncology Hematology, P.A.

Silver Spring, Maryland, 20904

Not Yet Recruiting

Minnesota Oncology Hematology, PA

Burnsville, Minnesota, 55337

Recruiting

Allina Health Cancer Institute - Mercy Hospital

Coon Rapids, Minnesota, 55433

Recruiting

Minnesota Oncology Hematology, PA

Coon Rapids, Minnesota, 55433

Recruiting

Minnesota Oncology Hematology, P.A.

Edina, Minnesota, 55435

Recruiting

Minnesota Oncology Hematology PA

Maple Grove, Minnesota, 55369

Recruiting

Minnesota Oncology Hematology, P.A.

Maplewood, Minnesota, 55109

Recruiting

Minnesota Oncology Hematology, P.A...

Minneapolis, Minnesota, 55404

Recruiting

Allina Health Cancer Institute - Abbott Northwestern Hospital

Minneapolis, Minnesota, 55407

Recruiting

Allina Health Cancer Institute - United Hospital

Saint Paul, Minnesota, 55102

Recruiting

Minnesota Oncology Hematology, PA

Woodbury, Minnesota, 55125

Recruiting

Missouri Cancer Associates

Columbia, Missouri, 65201

Recruiting

Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana

Billings, Montana, 59102

Not Yet Recruiting

Nebraska Medicine-Bellevue Medical Center

Bellevue, Nebraska, 68123

Not Yet Recruiting

Nebraska Medicine

Omaha, Nebraska, 68105

Not Yet Recruiting

Nebraska Medicine - Village Pointe

Omaha, Nebraska, 68118

Not Yet Recruiting

University Of Nebraska Medical Center

Omaha, Nebraska, 68198

Not Yet Recruiting

Essex Oncology of North Jersey

Belleville, New Jersey, 07109

Not Yet Recruiting

CHRISTUS St. Vincent Regional Cancer Center

Santa Fe, New Mexico, 87505

Not Yet Recruiting

Christus St. Vincent Regional Medical Center

Santa Fe, New Mexico, 87505

Not Yet Recruiting

Montefiore Medical Center - Montefiore Medical Park

The Bronx, New York, 10461

Recruiting

White Plains Hospital

White Plains, New York, 10601

Recruiting

Oncology Hematology Care Inc

Cincinnati, Ohio, 45211

Recruiting

Oncology Hematology Care

Cincinnati, Ohio, 45242

Recruiting

Oncology Hematology Care Inc

Cincinnati, Ohio, 45245

Recruiting

Oncology Hematology Care Inc

Fairfield, Ohio, 45014

Recruiting

Oncology Associates of Oregon, P.C.

Eugene, Oregon, 97401

Recruiting

Alliance Cancer Specialists, PC

Bensalem, Pennsylvania, 19020

Recruiting

Consultants in Medical Oncology and Hematology, P.C.

Broomall, Pennsylvania, 19008

Recruiting

Alliance Cancer Specialists, PC

Doylestown, Pennsylvania, 18901

Recruiting

Alliance Cancer Specialists, PC

Horsham, Pennsylvania, 19044

Recruiting

Alliance Cancer Specialists, P.C.

Langhorne, Pennsylvania, 19047

Recruiting

Alliance Cancer Specialists, PC

Media, Pennsylvania, 19063

Recruiting

Alliance Cancer Specialists, PC

Sellersville, Pennsylvania, 18960

Recruiting

Alliance Cancer Specialists, PC

Wynnewood, Pennsylvania, 19096

Recruiting

Tennessee Oncology, PLLC - Chattanooga Downtown

Chattanooga, Tennessee, 37403

Not Yet Recruiting

Tennessee Oncology, PLLC - Chattanooga Med Park II

Chattanooga, Tennessee, 37404

Not Yet Recruiting

Tennessee Oncology, PLLC - Chattanooga Memorial

Chattanooga, Tennessee, 37404

Not Yet Recruiting

Tennessee Oncology, PLLC - Investigational Drug Services/Supply Storage

Chattanooga, Tennessee, 37404

Not Yet Recruiting

Tennessee Oncology, PLLC - Cleveland

Cleveland, Tennessee, 37311

Not Yet Recruiting

Tennessee Cancer Specialists

Knoxville, Tennessee, 37909

Recruiting

Tennessee Oncology, PLLC - Lebanon

Lebanon, Tennessee, 37090

Not Yet Recruiting

Tennessee Oncology, PLLC - Mount Juliet

Mount Juliet, Tennessee, 37122

Not Yet Recruiting

Tennessee Oncology, PLLC - Murfreesboro

Murfreesboro, Tennessee, 37129

Not Yet Recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203

Not Yet Recruiting

Tennessee Oncology, PLLC - Investigational Drug Services

Nashville, Tennessee, 37203

Not Yet Recruiting

Tennessee Oncology, PLLC - Nashville Elliston Place Plaza Medical Oncology & Hematology Clinic

Nashville, Tennessee, 37203

Not Yet Recruiting

Tennessee Oncology, PLLC - Nashville Saint Thomas West

Nashville, Tennessee, 37205

Not Yet Recruiting

Tennessee Oncology, PLLC - Shelbyville

Shelbyville, Tennessee, 37160

Not Yet Recruiting

Tennessee Oncology, PLLC - Smyrna

Smyrna, Tennessee, 37167

Not Yet Recruiting

Texas Oncology - West Texas

Abilene, Texas, 79606

Recruiting

Texas Oncology-Northeast Texas

Allen, Texas, 75013

Recruiting

Texas Oncology- Central South.

Austin, Texas, 78705

Recruiting

Texas Oncology Central South

Austin, Texas, 78731

Recruiting

Texas Oncology- Central South.

Austin, Texas, 78745

Recruiting

Texas Oncology - Central South (Renfert Way)

Austin, Texas, 78758

Recruiting

Texas Oncology - Gulf Coast

Beaumont, Texas, 77702

Recruiting

The University of Texas, MD Anderson Cancer Center - Woodlands

Conroe, Texas, 77384

Recruiting

Texas Oncology - Dallas (Sammons)

Dallas, Texas, 75246

Recruiting

Texas Oncology-Northeast Texas

Denison, Texas, 75020

Recruiting

Texas Oncology-Northeast Texas

Denton, Texas, 76201

Recruiting

Texas Oncology-Northeast Texas

Flower Mound, Texas, 75028

Recruiting

Texas Oncology- Central South

Harlingen, Texas, 78550

Recruiting

The University of Texas MD Anderson Cancer Center Diagnostic Imaging

Houston, Texas, 77030

Recruiting

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting

The University of Texas, MD Anderson Cancer Center- Interventional Radiology

Houston, Texas, 77030

Recruiting

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting

The University of Texas MD Anderson Cancer Center Clinical Research Imaging

Houston, Texas, 77054

Recruiting

The University of Texas, MD Anderson Cancer Center - West Houston

Houston, Texas, 77079

Recruiting

US Oncology Investigational Product Center (IPC)

Irving, Texas, 75063

Recruiting

US Oncology Investigational Products Center (IPC)

Irving, Texas, 75063

Recruiting

US Oncology Investigational Products Center(IPC)

Irving, Texas, 75063

Recruiting

The University of Texas, MD Anderson Cancer Center - League City

League City, Texas, 77573

Recruiting

Texas Oncology-Northeast Texas

Lewisville, Texas, 75056

Recruiting

Texas Oncology-Northeast Texas

Longview, Texas, 75601

Recruiting

Texas Oncology

McAllen, Texas, 78503

Recruiting

Texas Oncology-Northeast Texas

McKinney, Texas, 75071

Recruiting

Texas Oncology-Northeast Texas

Palestine, Texas, 75801

Recruiting

Texas Oncology-Northeast Texas

Paris, Texas, 75460

Recruiting

Texas Oncology - Gulf Coast

Pearland, Texas, 77584

Recruiting

Baylor Scott & White Health - Round Rock

Round Rock, Texas, 78665

Not Yet Recruiting

The University of Texas, MD Anderson Cancer Center - Sugar Land

Sugar Land, Texas, 77478

Recruiting

Texas Oncology - Gulf Coast

Sugar Land, Texas, 77479

Recruiting

Texas Oncology - Gulf Coast

The Woodlands, Texas, 77380

Recruiting

Texas Oncology-Northeast Texas

Tyler, Texas, 75702

Recruiting

Texas Oncology- Central South

Waco, Texas, 76712

Recruiting

Texas Oncology-Central South

Waco, Texas, 76712

Recruiting

Texas Oncology - Central South

Weslaco, Texas, 78596

Recruiting

Blue Ridge Cancer Care

Blacksburg, Virginia, 24060

Not Yet Recruiting

Oncology & Hematology Associates of Southwest Virginia Inc dba Blue Ridge Cancer Care

Salem, Virginia, 24153

Not Yet Recruiting

Shenandoah Oncology, P.C.

Winchester, Virginia, 22601

Not Yet Recruiting

American Oncology Network Vista Oncology Division-West office

Olympia, Washington, 98502

Recruiting

American Oncology Network Vista Oncology Division-East office

Olympia, Washington, 98506

Recruiting