Actively Recruiting
Phase III Study Comparing Dato-DXd With or Without Osimertinib to Platinum Chemotherapy in Adults With EGFR-Mutated Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Progression
Led by AstraZeneca · Updated on 2026-05-14
744
Participants Needed
303
Research Sites
104 weeks
Total Duration
On this page
Sponsors
A
AstraZeneca
Lead Sponsor
D
Daiichi Sankyo
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the effects of Dato-DXd combined with osimertinib or Dato-DXd alone compared to platinum-based doublet chemotherapy in people with EGFR-mutated locally advanced or metastatic non-small cell lung cancer NSCLC whose disease progressed after prior osimertinib treatment. This Phase III, open-label, randomized study aims to compare progression-free survival among these treatments to better understand options for this condition. Participants are randomly assigned to one of three groups Dato-DXd plus osimertinib, Dato-DXd alone, or platinum-based doublet chemotherapy. Dato-DXd is given as an intravenous infusion every 3 weeks, osimertinib is taken orally daily, and chemotherapy involves pemetrexed combined with carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance pemetrexed. Treatments continue until disease progression, unacceptable side effects, or other reasons to stop. Throughout the study, participants undergo regular assessments including radiological scans to monitor tumor response using RECIST v1.1 criteria, safety evaluations, and health status measurements. After stopping treatment, an end-of-treatment visit occurs within 35 days, followed by safety follow-up 28 days after the last dose. The study primarily measures progression-free survival over up to 2.5 years, with additional outcomes including overall survival, response rates, quality of life, and pharmacokinetics monitored for up to 3.5 years.
CONDITIONS
Brief Title
A Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC).
- Documented EGFR mutation known to be sensitive to EGFR tyrosine kinase inhibitors.
- Disease progression on prior osimertinib monotherapy.
- Two or fewer prior lines of EGFR tyrosine kinase inhibitors.
- At least one measurable lesion not previously irradiated.
- WHO/ECOG performance status of 0 or 1.
- Adequate bone marrow and organ function within 7 days before randomization.
- Age between 18 and 130 years.
- Any gender.
You will not qualify if you...
- Use of chemotherapy, VEGF inhibitors, immunotherapy, or other anti-cancer therapy in the metastatic setting prior to randomization.
- Platinum-based chemotherapy in non-metastatic setting within 12 months before randomization.
- History of another primary malignancy within 2 years unless treated with curative intent and no active disease.
- Severe or uncontrolled systemic diseases including active bleeding, infection, interstitial lung disease (ILD)/pneumonitis, or cardiac disease.
- Significant fluid retention not manageable by drainage.
- History or current evidence of non-infectious ILD/pneumonitis requiring steroids or drug-induced ILD.
- Severe pulmonary compromise from other lung illnesses.
- Unstable spinal cord compression or brain metastases.
- Symptomatic brain metastases including leptomeningeal involvement.
- Clinically significant corneal disease.
- Uncontrolled infections requiring systemic treatment or recent antibiotic use.
- Known uncontrolled HIV infection.
Research Team
A
AstraZeneca Clinical Study Information Center
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