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First-line treatment for advanced non-small cell lung cancer with osimertinib and datopotamab deruxtecan

A Phase III, Open-label, Randomised Study of Osimertinib With or Without Datopotamab Deruxtecan (Dato-DXd), as First-line Treatment in Participants With Epidermal Growth Factor Receptor (EGFR) Mutation-positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer

Phase 3 Interventional AstraZeneca · NCT06350097

This study is testing if combining two treatments, osimertinib and datopotamab deruxtecan, can help people with advanced non-small cell lung cancer that has certain mutations feel better compared to just using osimertinib alone.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment582 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionsosimertinib, radiation, Datopotamab
Locations166 sites (Fountain Valley, California and 165 other locations)
Trial IDNCT06350097 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of osimertinib, a targeted therapy, in combination with datopotamab deruxtecan, an antibody-drug conjugate, compared to osimertinib alone in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that has specific EGFR mutations. The study is open-label and randomized, meaning both the researchers and participants know which treatment is being administered. Participants will receive treatment until disease progression or unacceptable toxicity occurs, with regular assessments to monitor their health and response to therapy. The trial is expected to last approximately 9 years and includes multiple research sites across California.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 or older with locally advanced or metastatic non-squamous NSCLC harboring specific EGFR mutations and who have not received prior systemic therapy.

Not a fit: Patients with squamous cell carcinoma or those who have previously received EGFR-targeted therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a more effective first-line therapy option for patients with advanced EGFR mutation-positive NSCLC.

How similar studies have performed: Other studies have shown promising results with osimertinib in treating EGFR mutation-positive NSCLC, suggesting that this combination approach may also be effective.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

Age

1. Participant must be ≥ 18 years.

   Type of Participant and Disease Characteristics
2. Histologically or cytologically documented nonsquamous NSCLC. NSCLC of mixed histology is allowed if adenocarcinoma is the predominant histology. Mixed small-cell lung cancer and NSCLC histology, and sarcomatoid variant of NSCLC is ineligible.
3. Stage IIIB or IIIC or Stage IV metastatic NSCLC or recurrent NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative surgery or definitive chemoradiation at the time of randomisation.
4. Participants must not have received prior EGFR TKIs or other systemic therapy for Stage IIIB, IIIC or IV NSCLC.
5. The tumour harbors at least 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other genomic alterations, which may include EGFR T790M, assessed by a CLIA-certified (US sites) or an accredited (outside of the US) local laboratory or by central prospective tissue testing.
6. For participants enrolled in randomisation period, mandatory provision of an unstained, archival tumour tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status.
7. WHO performance status of 0 or 1.
8. At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with CT or MRI and is suitable for accurate repeated measurements.
9. Adequate bone marrow reserve and organ function before the first dose of study intervention.

Exclusion Criteria:

1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, history of allogenic organ transplant which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
2. Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of osimertinib.
3. History of another primary malignancy.
4. Spinal cord compression and/or unstable brain metastases, as defined by Protocol.
5. Clinically significant corneal disease.
6. Has active or uncontrolled hepatitis B or C virus infection, as defined by Protocol.
7. Past medical history of ILD/penumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
8. Pulmonary embolism within 3 months of the study enrolment or has severe pulmonary function compromise.
9. Has clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.

Where this trial is running

Fountain Valley, California and 165 other locations

+116 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 CancerNon-small Cell Lung Cancer, NSCLC, Epidermal Growth Factor Receptor Mutation-positive, Osimertinib, Dato-DXd, Datopotamab Deruxtecan, Tagrisso
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.