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First-line treatment for advanced non-squamous lung cancer with high PD-L1 expression

A Phase III, Randomised, Open-label, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Pembrolizumab Monotherapy for the First-line Treatment of Participants With Locally-advanced or Metastatic Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations (TROPION-Lung10)

Phase 3 Interventional AstraZeneca · NCT06357533

This study is testing a new combination treatment for patients with advanced non-squamous lung cancer that has high PD-L1 levels to see if it works better than current options.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment675 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionsradiation, pembrolizumab, Datopotamab
Locations281 sites (Anchorage, Alaska and 280 other locations)
Trial IDNCT06357533 on ClinicalTrials.gov

What this trial studies

This Phase III, open-label study evaluates the efficacy and safety of Datopotamab Deruxtecan (Dato-DXd) in combination with Rilvegostomig compared to Rilvegostomig alone and Pembrolizumab monotherapy. It targets patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that exhibit high PD-L1 expression and lack actionable genomic alterations. Participants will be randomized to receive one of the treatment regimens, and their tumor samples will be analyzed for biomarker status. The study aims to determine the best first-line therapy for this specific patient population.

Who should consider this trial

Good fit: Ideal candidates include adults with advanced non-squamous NSCLC, high PD-L1 expression (TC ≥ 50%), and no actionable genomic alterations.

Not a fit: Patients with squamous cell histology or those who have received prior systemic therapy for advanced/metastatic NSCLC may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective first-line treatment option for patients with advanced non-squamous NSCLC and high PD-L1 expression.

How similar studies have performed: Other studies have shown promising results with similar approaches in treating advanced NSCLC, indicating potential for success in this trial.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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 Criteria:

* 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 this trial is running

Anchorage, Alaska and 280 other locations

+231 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Non-Small Cell Lung CancerNSCLCDatopotamab DeruxtecanRilvegostomigPembrolizumabNon-squamousPD-L1 expression >=50%Locally-advanced NSCLC
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.