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Phase III Study of Dato-DXd and Rilvegostomig for Advanced Non-Small Cell Lung Cancer

This Phase III study is looking for people with advanced non-squamous non-small cell lung cancer (NSCLC) that has high levels of a protein called PD-L1 (TC ≥ 50%) and no specific genetic changes (actionable genomic alterations) that doctors usually target. The study is comparing two treatment approaches: Datopotamab Deruxtecan (Dato-DXd) combined with Rilvegostomig, or Rilvegostomig alone, against a standard treatment called Pembrolizumab. All these medicines are given intravenously (into a vein). Researchers want to see how well these treatments prevent the cancer from growing (Progression-Free Survival) and how long people live (Overall Survival). To join, you must be at least 18 years old and have specific types of NSCLC, confirmed by tests for certain biomarkers like ALK, EGFR, PD-L1, and ROS1. The study aims to enroll 675 participants, but its current status is unclear.

Study design
This is a Phase III, randomized, open-label study involving 675 planned participants. It compares different drug combinations as a first-line treatment.
What's involved
Not specified in the trial record.
Compensation
Not stated in the trial record.
Follow-up
Participants will be followed to measure Progression-Free Survival for approximately 4 years and Overall Survival for approximately 6 years.

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NCT06357533

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
PHASE3Ages 18+InterventionalTreatment
AstraZeneca
~675 participants
Updated 2026-08-12 on ClinicalTrials.gov
What's tested:Datopotamab DeruxtecanRilvegostomigPembrolizumab

At a glance

Recruiting sites
238 of 287 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Progression-Free Survival (PFS) in TROP2 biomarker positive participants.
Measured over Approximately 4 years
+1 more outcome measured

Conditions

Non-Small Cell Lung Cancer

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Where it's being run

287 sites across 55 states
China39
Japan28
Germany21
Hungary11
India11
Brazil10
Italy10
Taiwan10

Study leadership

  • Suresh S. Ramalingam, MD · PRINCIPAL_INVESTIGATOR · Emory University, Atlanta, Georgia, United States of America.

Who to contact

AstraZeneca Clinical Study Information Center
[email protected]
1-877-240-9479
Email the study team

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Eligibility criteria

Inclusion

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

Exclusion

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

What this trial measures

  • Progression-Free Survival (PFS) in TROP2 biomarker positive participants.Approximately 4 years

    PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression, in the following population: • TROP2 biomarker positive population The measure of interest is the HR of PFS. PFS by investigator will be reported as a sensitivity analysis.

  • Overall Survival (OS) in TROP2 biomarker positive participants.Approximately 6 years

    OS is defined as the time from randomisation until the date of death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anti-cancer therapy, in the following population: • TROP2 biomarker positive population The measure of interest is the HR of OS.