Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations
This is a Phase III, randomized, open-label, multicenter, global study to compare the efficacy and safety of Datopotamab Deruxtecan (Dato-DXd) in combination with durvalumab and carboplatin compared with pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment of adults with stage IIIB, IIIC, or IV NSCLC without actionable genomic alterations (including sensitizing EGFR mutations, and ALK and ROS1 rearrangements).
Ask AI to explain this studyKey things to know
This describes the study’s primary purpose.
Plus 5 other study approaches.
These are broad labels—not an eligibility decision.
Checked against the public recordLast updated Oct 9, 2026 · Source: ClinicalTrials.gov
The study is underway but is not accepting new participants.
Interventional
Locations may change over time.
Study sponsor
What this study is about
- Purpose
- Treatment
- Study type
- Interventional
- Phase
- Phase 3
- Sponsor
- AstraZeneca
- Interventions being studied
- Drug: Datopotamab deruxtecan; Drug: Durvalumab; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Cisplatin; Drug: Pemetrexed; Drug: Paclitaxel
How this study is categorized
These labels come from structured fields and exact terms in the public record.
Who may be able to participate
The sponsor separates these requirements into two groups. You do not need to interpret them alone—use them to guide a conversation with the study team.
- Inclusion:
- Participants ≥ 18 years at screening
- Histologically or cytologically documented NSCLC that at the time of randomisation is Stage IIIB or IIIC disease not amenable to surgical resection or definitive chemoradiation or Stage IV metastatic disease
- Lacks sensitising EGFR tumour tissue mutation and ALK and ROS1 rearrangements and has no documented tumour genomic alterations in NTRK, BRAF, RET, MET or other actionable driver oncogenes with approved and available therapies (actionable genomic alterations). Testing is not required for tumors with squamous histology, with exceptions.
- ECOG PS of 0 or 1
- Archival tumour tissue
- Has adequate bone marrow reserve and organ function within 7 days before randomization Exclusion:
- Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC
- History of another primary malignancy with exceptions
- Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade ≤ 1 or baseline, with exceptions.
- Spinal cord compression or clinically or radiologically active brain metastases
- History of leptomeningeal carcinomatosis.
- Known active or uncontrolled hepatitis B or C virus infection.
- Uncontrolled or suspected infection requiring IV antibiotics, antivirals, or antifungals.
- Clinically significant corneal disease
- History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.
U.S. locations
- Research SitePhoenix, Arizona
- Research SiteTucson, Arizona
- Research SiteHot Springs, Arkansas
- Research SiteLittle Rock, Arkansas
- Research SiteSpringdale, Arkansas
- Research SiteFountain Valley, California
- Research SiteLos Angeles, California
- Research SiteOrange, California
- Research SiteBoulder, Colorado
- Research SiteFort Myers, Florida
- Research SiteJacksonville, Florida
- Research SiteSt. Petersburg, Florida
Source and freshness
Processed from ClinicalTrials.gov. Last public update: Oct 9, 2026. Always confirm current availability with the study team.