Recruiting
Phase 3

Dato-DXd & Osimertinib

Sponsor:

AstraZeneca

Code:

NCT06417814

Conditions

Metastatic Non-small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Dato-DXd

Osimertinib

Pemetrexed

Carboplatin

Cisplatin

Study Details

Brief summary:

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).

Conditions

Metastatic Non-small Cell Lung Cancer

Study ID

NCT06417814

Start date

Oct 4, 2024

Status verified date

May, 2026

Completion date

Sep 27, 2028

Anticipated

Primary completion date

Sep 30, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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 systemic antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections. Use of systemic antibiotics within 14 days of randomization.
  • Has known human immunodeficiency virus (HIV) infection that is not well controlled.

Study Design

Enrollment

744 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Group 1: Dato-DXd + Osimertinib Combination Therapy

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, 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.

experimental: Group 2: Dato-DXd Monotherapy

Participants will receive Dato-DXd 6 mg/kg as IV infusion 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.

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.

Interventions

Dato-DXd

Dato-DXd will be administered as IV infusion.

Osimertinib

Osimertinib will be administered orally.

Pemetrexed

Pemetrexed will be administered as IV infusion.

Carboplatin

Carboplatin will be administered as IV infusion.

Cisplatin

Cisplatin will be administered as IV infusion.

Primary outcome measure

  • Progression free Survival (PFS) [ Time Frame: Up to 2.5 years ]

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

1-877-240-9479information.center@astrazeneca.com

Locations

Research Site

Recruiting

Fayetteville, Arkansas, United States, 72703

Research Site

Recruiting

Fountain Valley, California, United States, 92708

Research Site

Recruiting

La Jolla, California, United States, 92093

Research Site

Recruiting

San Diego, California, United States, 92123

Research Site

Recruiting

Colorado Springs, Colorado, United States, 80909

Research Site

Recruiting

Fort Collins, Colorado, United States, 80528

Research Site

Recruiting

Jacksonville, Florida, United States, 32256

Research Site

Recruiting

Athens, Georgia, United States, 30607

Research Site

Recruiting

Chicago, Illinois, United States, 60611

Research Site

Recruiting

Evanston, Illinois, United States, 60201

Research Site

Recruiting

Louisville, Kentucky, United States, 40207

Research Site

Recruiting

Baltimore, Maryland, United States, 21201

Research Site

Recruiting

Bethesda, Maryland, United States, 20817

Research Site

Recruiting

Boston, Massachusetts, United States, 02215

Research Site

Recruiting

Detroit, Michigan, United States, 48202

Research Site

Recruiting

Kansas City, Missouri, United States, 64132

Research Site

Recruiting

Omaha, Nebraska, United States, 68124

Research Site

Recruiting

Morristown, New Jersey, United States, 07960

Research Site

Recruiting

Northfield, New Jersey, United States, 08225

Research Site

Recruiting

New York, New York, United States, 10065

Research Site

Recruiting

The Bronx, New York, United States, 10461

Research Site

Recruiting

Maumee, Ohio, United States, 43537

Research Site

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Research Site

Recruiting

Chattanooga, Tennessee, United States, 37404

Research Site

Recruiting

Nashville, Tennessee, United States, 37203

Research Site

Recruiting

Fairfax, Virginia, United States, 22031

Research Site

Recruiting

Brampton, Ontario, Canada, L6R 3J7

Research Site

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Research Site

Recruiting

Toronto, Ontario, Canada, M5G 1Z5

Research Site

Recruiting

Montreal, Quebec, Canada, H4A 3J1

Research Site

Recruiting

Québec, Quebec, Canada, G1R 2J6

More Information

Sponsor

AstraZeneca

Last update posted

May 14, 2026

Last verified

May, 2026

Keywords

  • Epidermal growth factor receptor gene mutation
  • Standard of Care
  • Locally, advanced carcinoma
  • Metastatic carcinoma
  • Non-small cell lung cancer
  • Dato-dxd
  • Datopotamab deruxtecan
  • Osimertinib
  • Tagrisso
  • Pemetrexed
  • Carboplatin
  • Cisplatin

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by AstraZeneca on 2026-05-14.