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

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 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.

Why it matters

Who can join: the full rules

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.
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. Has clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.

Where it's running

• Research Site
  Los Alamitos, California, United States Recruiting
• Research Site
  Los Angeles, California, United States Recruiting
• Research Site
  Los Angeles, California, United States Recruiting
• Research Site
  Orange, California, United States Recruiting
• Research Site
  San Diego, California, United States Recruiting
• Research Site
  Santa Monica, California, United States Recruiting

+117 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center
• Email: information.center@astrazeneca.com
• Phone: 1-877-240-9479

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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.