Dato-DXd and Pembrolizumab for Advanced Lung Cancer
This study is testing a new combination of medicines, Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab, against Pembrolizumab alone. It's for people with advanced or metastatic non-small cell lung cancer (NSCLC) that has not spread to other parts of the body and does not have certain genetic changes. The goal is to see if the combination treatment helps people live longer without their cancer getting worse (progression-free survival) or live longer overall (overall survival). To join, you must be at least 18 years old and have specific levels of a marker called PD-L1 in your tumor. The study is currently recruiting participants.
- Study design
- This study plans to enroll 740 participants who will be randomly assigned to receive either Pembrolizumab alone or Dato-DXd plus Pembrolizumab. The study will compare how well these treatments work.
- What's involved
- You will receive intravenous (IV) infusions of the study medicine every 3 weeks on Day 1 of each 21-day cycle. You will also go through screening, treatment, and follow-up periods.
- Compensation
- Not stated in the trial record.
- Follow-up
- Participants will be followed for progression-free survival for up to approximately 44 months, and for overall survival for up to approximately 71 months.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05215340
Study of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in the First-line Treatment of Subjects With Advanced or Metastatic NSCLC Without Actionable Genomic Alterations
Active, Not Recruiting
PHASE3Ages 18+InterventionalTreatmentDaiichi Sankyo
~740 participants
Updated 2026-08-19 on ClinicalTrials.gov
What's tested:Datopotamab DeruxtecanPembrolizumab
At a glance
Recruiting sites
0 of 234 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Progression-free Survival Based on Blinded Independent Central Review in Participants With Non-Squamous Histology Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab
Measured over From randomization until disease progression or death (whichever occurs first), up to approximately 46 months
+1 more outcome measured
Conditions
Where it's being run
234 sites across 70 statesChina27
France13
Spain12
Brazil10
Italy10
Texas9
Argentina9
Taiwan9
Study leadership
- Global Clinical Leader · STUDY_DIRECTOR · Daiichi Sankyo
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Sign and date the Tissue Screening and Main Informed Consent Forms, prior to the start of any study-specific qualification procedures.
Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time of informed consent.
Histologically documented non-squamous NSCLC that meets all of the following criteria (Note: Subjects with squamous histology were eligible prior to Protocol Version 5.0. After Protocol Version 5.0, subjects with squamous histology are not eligible. Subjects with mixed histology, including those with a squamous component, remain eligible the study even after Protocol Version 5.0):
Has provided a formalin-fixed tumor tissue sample for the measurement of trophoblast cell surface protein 2 (TROP2) protein expression and for the assessment of other exploratory biomarkers.
Tumor has high programmed death receptor-1 (PD-L1) expression (TPS ≥50%) as determined by PD-L1 immunohistochemistry (IHC) 22C3 pharmDx assay by central testing (minimum of 6 slides).
Has an adequate treatment washout period before Cycle 1 Day 1.
Measurable disease based on local imaging assessment using RECIST Version 1.1.
Has left ventricular ejection fraction (LVEF) ≥50% by either an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 28 days before randomization.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at screening.
Has a life expectancy of at least 3 months.
Adequate bone marrow function within 7 days before randomization.
Exclusion
Has received prior systemic treatment for advanced or metastatic NSCLC.
Has received prior treatment for NSCLC with any of the following, including in the adjuvant/neoadjuvant setting:
Has spinal cord compression or active and untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases and who are asymptomatic may participate provided they are radiologically stable.
Has received prior radiotherapy \< 4 weeks of start of study intervention or more than 30 Gy (unit of ionizing radiation dose in the International System of Units) to the lung within 6 months of Cycle 1 Day 1.
History of another primary malignancy (beyond NSCLC) except for:
Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
Clinically severe pulmonary compromise, as judged by the investigator, resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement or prior complete pneumonectomy.
Uncontrolled or significant cardiovascular disease, including:
Clinically significant corneal disease.
Has received a live vaccine or live-attenuated vaccine (messenger ribonucleic acid and replication-incompetent adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of study drug. For any participant receiving an approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine, please follow the vaccine label and/or local guidance.
Active, known, or suspected autoimmune disease (has an active autoimmune disease that has required systemic treatment in the past 2 years).
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosage \>10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy ≤7 days prior to the first dose of study drug.
Has known human immunodeficiency virus (HIV) infection that is not well controlled.
Has an active hepatitis or uncontrolled hepatitis B or active hepatitis C infection.
Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
Had an allogeneic tissue/solid organ transplant.
Has a history of severe hypersensitivity reactions to either the drug or inactive ingredients (including but not limited to polysorbate 80) of Dato-DXd or pembrolizumab.
What this trial measures
- Progression-free Survival Based on Blinded Independent Central Review in Participants With Non-Squamous Histology Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With PembrolizumabFrom randomization until disease progression or death (whichever occurs first), up to approximately 46 months
Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.
- Overall Survival (OS) in Participants With Non-Squamous Histology Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With PembrolizumabFrom randomization until date of death due to any cause, up to approximately 72 months
Overall Survival (OS) is defined as the time from randomization to death due to any cause.