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

Actively Recruiting

Phase 3

Age: 18Years +

All Genders

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

Led by Daiichi Sankyo · Updated on 2026-05-13

740

Participants Needed

243

Research Sites

321 weeks

Total Duration

AI-Summary

What this Trial Is About

This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab alone in participants with advanced or metastatic non-small cell lung cancer (NSCLC) of non-squamous histology.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years +

All Genders

Eligibility Criteria

You may qualify if you...

Adults aged 18 years or older at the time of informed consent
Histologically confirmed non-squamous non-small cell lung cancer (NSCLC) with stage IIIB, IIIC, or IV disease not suitable for surgery or definitive chemoradiation
Negative test results for EGFR, ALK, and ROS1 actionable genomic alterations; KRAS mutations allowed
Tumor with high PD-L1 expression (TPS 6550%) confirmed by central testing
Provided tumor tissue sample for TROP2 protein expression and other biomarker assessments
Measurable disease by local imaging using RECIST 1.1 criteria
Left ventricular ejection fraction (LVEF) 6550% by echocardiogram or MUGA scan within 28 days before randomization
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Life expectancy of at least 3 months
Adequate bone marrow function within 7 days before randomization
Completed any required treatment washout period before Cycle 1 Day 1
Signed informed consent forms before study-specific procedures

You will not qualify if you...

Prior systemic treatment for advanced or metastatic NSCLC
Prior treatment with agents targeting topoisomerase I, TROP2, PD-1, PD-L1, PD-L2, or other immune checkpoint inhibitors
Spinal cord compression or active, untreated central nervous system metastases or carcinomatous meningitis
Radiotherapy within 4 weeks before study treatment start or lung radiation exceeding 30 Gy within 6 months before Cycle 1 Day 1
History of other primary malignancies within 3 years except certain treated cancers without active disease
History or current interstitial lung disease or pneumonitis requiring steroids
Severe pulmonary compromise or prior complete pneumonectomy
Uncontrolled or significant cardiovascular disease including recent myocardial infarction, uncontrolled angina, low LVEF, heart failure class 2-4, uncontrolled hypertension
Clinically significant corneal disease
Live vaccine within 30 days before first study drug dose
Active or recent autoimmune disease requiring systemic treatment
Immunodeficiency or chronic immunosuppressive therapy within 7 days before first study drug dose
Uncontrolled HIV or active hepatitis B or C infection
Uncontrolled infection needing intravenous antibiotics, antivirals, or antifungals
History of allogeneic tissue or solid organ transplant
Severe allergic reactions to study drugs or their ingredients

AI-Screening

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Trial Site Locations

Total: 243 locations

Ironwood Cancer and Research Center

Chandler, Arizona, United States, 85224

Actively Recruiting

UCLA HemOnc - Clinical Research Unit

Los Angeles, California, United States, 90095

Actively Recruiting

Compassionate Cancer Care Medical Group

Riverside, California, United States, 92501

Withdrawn

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States, 94158

Withdrawn

Ridley-Tree Cancer Center

Santa Barbara, California, United States, 93105

Actively Recruiting

PIH Health Whittier Hospital

Whittier, California, United States, 90602

Actively Recruiting

The Oncology Institute of Hope and Innovation

Whittier, California, United States, 90603

Terminated

Uch-Mhs D/B/A Memorial Health System

Colorado Springs, Colorado, United States, 80909

Actively Recruiting

Johns Hopkins University

Baltimore, Maryland, United States, 21205

Actively Recruiting

American Oncology Partners of Maryland

Bethesda, Maryland, United States, 20817

Actively Recruiting

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02115

Actively Recruiting

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Actively Recruiting

DFCI - Steward St. Elizabeth's Medical Center

Boston, Massachusetts, United States, 02215

Withdrawn

Dana Farber Cancer Institute - Foxborough

Foxborough, Massachusetts, United States, 02035

Terminated

Dana Farber Cancer Institute - Milford Medical Center

Milford, Massachusetts, United States, 01757

Withdrawn

DFCI - South Shore Hospital

South Weymouth, Massachusetts, United States, 02190

Terminated

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States, 03766

Actively Recruiting

Astera Cancer Care

East Brunswick, New Jersey, United States, 08816

Actively Recruiting

Regional Cancer Care Associates LLC

Freehold, New Jersey, United States, 07728

Actively Recruiting

Cooperman Barnabas Medical Center

New Brunswick, New Jersey, United States, 08901

Actively Recruiting

The Valley Hospital

Paramus, New Jersey, United States, 07652

Actively Recruiting

Montefiore Medical Center

The Bronx, New York, United States, 10461

Actively Recruiting

Arizona Oncology NAHOA