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

Recruiting now · Phase 3

Conditions studied: Non-Small Cell Lung Cancer

In brief

The purpose of this study is to evaluate efficacy and safety of Dato-DXd in combination with rilvegostomig or rilvegostomig monotherapy compared with pembrolizumab monotherapy as a first line therapy in participants with locally advanced or metastatic non-squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.

Key facts

Study ID

NCT06357533

Run by

AstraZeneca

People needed

675

Starts

2024-04-11

Expected to finish

2029-12-28

Last updated by the study team

2026-07-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically or cytologically documented non-squamous NSCLC.
• Stage IIIB or IIIC or Stage IV metastatic NSCLC (according to Edition 8 of the AJCC staging manual) not amenable to curative surgery or definitive chemoradiation.
• Absence of sensitising EGFR mutations, and ALK and ROS1 rearrangements, and absence of documented local test result for any other known genomic alteration for which there are locally approved and available targeted first-line therapies.
• Must provide tumor sample to determine PD-L1 status, TROP2 status and other biomarkers.
• Known tumour PD-L1 expression status defined as TC ≥ 50%
• At least one lesion, not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline
• ECOG performance status of 0 or 1
• Adequate bone marrow reserve and organ function

You may not qualify if…

• Prior systemic therapy for advanced/metastatic NSCLC.
• Squamous cell histology, or predominantly squamous cell histology NSCLC; mixed small cell lung cancer; NSCLC histology, sarcomatoid variant.
• History of another primary malignancy within 3 years
• Active or prior documented autoimmune or inflammatory disorders (with exceptions)
• Any evidence of severe or uncontrolled disease that makes it undesirable for the participant to participate in the study or that would jeopardies compliance with the protocol.
• Has clinically significant third-space fluid retention (for example pleural effusion) and is not amenable for repeated drainage.
• History of any ILD/pneumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, has current or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Has significant pulmonary function compromise, as determined by the investigator
• Spinal cord compression, or brain metastases unless participant treated and no longer symptomatic, radiologically stable, and who require no treatment with corticosteroids or anticonvulsants.
• History of leptomeningeal carcinomatosis
• Known clinically significant corneal disease
• Active infection with TB, HBV, HCV, Hepatitis A, or known HIV infection that is not well controlled
• History of active primary immunodeficiency

Where it is running

• Research Site — Farmington Hills, Michigan, United States (enrolling)
• Research Site — Grand Rapids, Michigan, United States (enrolling)
• Research Site — Dearborn, Michigan, United States (enrolling)
• Research Site — Anaheim, California, United States (enrolling)
• Research Site — Beverly Hills, California, United States (enrolling)
• Research Site — Little Rock, Arkansas, United States (enrolling)
• Research Site — Tucson, Arizona, United States (enrolling)
• Research Site — Anchorage, Alaska, United States (enrolling)
• Research Site — Gainesville, Florida, United States (enrolling)
• Research Site — Miami Beach, Florida, United States (enrolling)
• Research Site — Orange City, Florida, United States (enrolling)
• Research Site — Orlando, Florida, United States (enrolling)
• Research Site — Fountain Valley, California, United States (enrolling)
• Research Site — West Palm Beach, Florida, United States (enrolling)
• Research Site — Springdale, Arkansas, United States (enrolling)
• Research Site — Atlanta, Georgia, United States (enrolling)
• Research Site — Atlanta, Georgia, United States (enrolling)
• Research Site — Clermont, Florida, United States (enrolling)
• Research Site — Hinsdale, Illinois, United States (enrolling)
• Research Site — Noblesville, Indiana, United States (enrolling)
• Research Site — Paducah, Kentucky, United States (enrolling)
• Research Site — Annapolis, Maryland, United States (enrolling)
• Research Site — Boston, Massachusetts, United States (enrolling)
• Research Site — Boston, Massachusetts, United States (enrolling)
• Research Site — Hattiesburg, Mississippi, United States (enrolling)

Full record on ClinicalTrials.gov

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