Actively Recruiting
Phase III Study of Datopotamab Deruxtecan with Rilvegostomig or Rilvegostomig Alone Compared to Pembrolizumab First-line Treatment for Advanced Non-squamous NSCLC with High PD-L1 Expression TC 50% Without Targetable Genomic Changes
Led by AstraZeneca · Updated on 2026-08-12
675
Participants Needed
287
Research Sites
N/A
Total Duration
On this page
Sponsors
A
AstraZeneca
Lead Sponsor
D
Daiichi Sankyo
Collaborating Sponsor
AI-Summary
What this Trial Is About
This research aims to assess the effectiveness and safety of Datopotamab Deruxtecan Dato-DXd combined with rilvegostomig or rilvegostomig alone compared to pembrolizumab alone as initial treatment in participants with locally advanced or metastatic non-squamous non-small cell lung cancer NSCLC that has high PD-L1 expression tumor cells 50% and no actionable genetic alterations. This Phase III, randomized, open-label global study focuses on patients who have not received previous systemic therapy for advanced disease. Participants are randomly assigned to one of three groups one group receives Dato-DXd plus rilvegostomig, another receives rilvegostomig alone, and the third receives pembrolizumab alone. All treatments are given as intravenous infusions every three weeks on the first day of each 21-day cycle. The study evaluates these treatments as first-line therapy for eligible participants. During the study, participants will have regular assessments including tumor evaluations and biomarker testing to monitor disease progression, overall survival, and response rates. Patient-reported symptoms and quality of life will also be measured. The study may last up to approximately six years to capture long-term outcomes. Safety monitoring and pharmacokinetics assessments are included throughout the trial to understand treatment effects and immune responses.
CONDITIONS
Brief Title
Phase III, Open-label, Study of First-line Dato-DXd in Combination With Rilvegostomig for Advanced Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically or cytologically confirmed non-squamous non-small cell lung cancer
- Stage IIIB, IIIC, or Stage IV metastatic NSCLC not suitable for curative surgery or definitive chemoradiation
- No sensitising EGFR mutations, ALK or ROS1 rearrangements, or other actionable genomic alterations with approved targeted therapies
- Must provide tumor sample for PD-L1, TROP2, and other biomarker testing
- Tumor PD-L1 expression status with tumor cells ≥ 50%
- At least one measurable lesion not previously irradiated
- ECOG performance status of 0 or 1
- Adequate bone marrow reserve and organ function
You will not qualify if you...
- Prior systemic therapy for advanced or metastatic NSCLC
- Squamous or predominantly squamous cell NSCLC, mixed small cell lung cancer, or sarcomatoid variant histology
- History of another primary cancer within the past 3 years
- Active or prior autoimmune or inflammatory disorders (with exceptions)
- Severe or uncontrolled diseases making participation unsafe or compliance difficult
- Clinically significant third-space fluid retention not manageable by drainage
- History or current evidence of interstitial lung disease or pneumonitis not ruled out by imaging
- Significant pulmonary function impairment
- Spinal cord compression or brain metastases unless treated, stable, and asymptomatic without corticosteroids or anticonvulsants
- History of leptomeningeal carcinomatosis
- Clinically significant corneal disease
- Active infections with tuberculosis, hepatitis B, hepatitis C, hepatitis A, or uncontrolled HIV
- History of active primary immunodeficiency
Research Team
A
AstraZeneca Clinical Study Information Center
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