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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Research Site
  Anchorage, Alaska, United States Recruiting
• Research Site
  Tucson, Arizona, United States Recruiting
• Research Site
  Little Rock, Arkansas, United States Recruiting
• Research Site
  Springdale, Arkansas, United States Recruiting
• Research Site
  Anaheim, California, United States Recruiting
• Research Site
  Beverly Hills, California, United States Recruiting

+240 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Principal investigator: Suresh S. Ramalingam, MD — Emory University, Atlanta, Georgia, United States of America.
• Study coordinator: AstraZeneca Clinical Study Information Center
• Email: information.center@astrazeneca.com
• Phone: 1-877-240-9479

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.