Print Send My Information

Purpose

This study will assess the effect of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in terms of progression-free survival (PFS).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Histologically or cytologically confirmed non-squamous NSCLC. - Must have evidence of documented pre-existing EGFRm information (EGFRm known to be associated with (epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKis] sensitivity [Ex19del, L858R, G719X, S768I, or L861Q], either alone or in combination with other EGFR mutations, which may include T790M). - Documented extra-cranial radiologic progression on prior osimertinib monotherapy (as most recent line of treatment) in the adjuvant, locally advanced, or metastatic setting. - Less than or equal to (<=2) prior lines of EGFR TKIs (osimertinib is the only permitted prior third generation EGFR TKI). - At least one lesion, not previously irradiated, that qualifies as a RECIST v1.1 TL at baseline and can be accurately measured at baseline. - World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. - Adequate bone marrow reserve and organ function within 7 days before randomization.

Exclusion Criteria

  • Use of chemotherapy, vascular endothelial growth factor inhibitor, immunotherapy or any anti-cancer therapy in the metastatic setting. Platinum-based chemotherapy in non-metastatic setting within 12 months prior to randomization. - History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention. - Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease. - Has significant third-space fluid retention (example [eg.], ascites or pleural effusion) as judged by the investigator and is not amenable for required repeated drainage. - History of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids or drug-induced ILD, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. - Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses. - Unstable spinal cord compression and/or unstable brain metastases. - Participants with symptomatic brain metastases (including leptomeningeal involvement). - Clinically significant corneal disease. - Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections. - Has known human immunodeficiency virus (HIV) infection that is not well controlled.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Group 1: Dato-DXd + Osimertinib Combination Therapy 		Participants will receive Dato-DXd 6 mg/kg as IV infusion Q3W on Day 1 of every 21-day cycle, and osimertinib 80 milligrams (mg) once daily (QD) orally, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met.
  • Drug: Dato-DXd
    Dato-DXd will be administered as IV infusion.
    Other names:
    • DS-1062a
  • Drug: Osimertinib
    Osimertinib will be administered orally.
    Other names:
    • Tagrisso
    • AZD9291
Experimental
Group 2: Dato-DXd Monotherapy 		Participants will receive Dato-DXd 6 milligrams per kilogram (mg/kg) as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of every 21-day cycle, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met.
  • Drug: Dato-DXd
    Dato-DXd will be administered as IV infusion.
    Other names:
    • DS-1062a
Experimental
Group 3: Platinum-based Doublet Chemotherapy 		Participants will receive pemetrexed 500 milligrams per meter square (mg/m2) in combination with carboplatin (AUC5) or cisplatin 75 mg/m2 as IV infusion Q3W for 4 cycles followed by pemetrexed maintenance 500 mg/m2 as IV infusion Q3W, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or another discontinuation criterion is met.
  • Drug: Pemetrexed
    Pemetrexed will be administered as IV infusion.
  • Drug: Carboplatin
    Carboplatin will be administered as IV infusion.
  • Drug: Cisplatin
    Cisplatin will be administered as IV infusion.

Recruiting Locations

Research Site
Fayetteville, Arkansas 72703

Research Site
Fountain Valley, California 92708

Research Site
La Jolla, California 92093

Research Site
Athens, Georgia 30607

Research Site
Bethesda, Maryland 20817

Research Site
Detroit, Michigan 48202

Research Site
Morristown, New Jersey 07960

Research Site
Northfield, New Jersey 08225

Research Site
Bronx, New York 10461

Research Site
New York, New York 10065

Research Site
Chattanooga, Tennessee 37404

Research Site
Nashville, Tennessee 37203

Research Site
Fairfax, Virginia 22031

More Details

NCT ID
NCT06417814
Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

Detailed Description

This is a Phase III, open-label, 3-arm, multicenter study assessing the effects of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in participants with epidermal growth factor receptor gene mutation (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on prior osimertinib treatment. Participants will be randomized in a 1:1:1 ratio to one of the following intervention groups: 1. Dato-DXd + osimertinib combination therapy 2. Dato-DXd monotherapy 3. Platinum-based doublet chemotherapy Participants will receive study intervention until Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) -defined radiological progression by the investigator, unacceptable toxicity, or other discontinuation criterion is met. After study intervention discontinuation, all participants will undergo an end of treatment (EoT) visit within 35 days of discontinuation and will be followed up for safety assessments 28 (+ 7) days after their last dose of study intervention.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.

For help using this page: trialstoday@researchmatch.org or call 855-514-7001

ResearchMatch is funded in part by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, led by the NIH’s National Center for Advancing Translational Sciences (NCATS), grants UL1TR000445 and 1U54RR032646-01, and grant U24TR001579 from NCATS and the National Library of Medicine. The content of this website is solely the responsibility of ResearchMatch and Vanderbilt University and does not necessarily represent the official views of the NIH, NCATS, or NLM.

Vanderbilt University Medical Center