Phase III, Open-label Study of First-line Osimertinib With or Without Datopotamab Deruxtecan for EGFRm Locally Advanced or Metastatic Non-small Cell Lung Cancer

Recruiting · NCT06350097 · Interventional (participants receive a specific treatment) · Lead sponsor: AstraZeneca

View the official record on ClinicalTrials.gov →

Interventions studied

What this trial is about

The purpose of this study is to evaluate efficacy and safety of osimertinib (tablet) in combination with Dato-DXd (i.v. infusion) compared with osimertinib (tablet) monotherapyas a first-line therapy in participants with locally advanced or metastatic EGFRm (Ex19del and/or L858R) NSCLC. Study details include: 1. The study duration will be event-driven, with an estimated duration of approximately 8 years. 2. Participants may receive study treatment until disease progression, unacceptable toxicity, or other specific discontinuation criteria are met. 3. The visit frequency will be every 3 weeks during the treatment period. Note: Participants on osimertinib treatment(osimertinib only arm or who have discontinued Dato-DXd while are still receiving osimertinib) are required to attend visits to perform assessments every 6 weeks from Cycle 7 until Cycle 17 and then visits every 12 weeks until disease progression or IP discontinuation. Participants who are receiving osimertinib + Dato-DXd are still required to attend visit to perform assessment every 3 weeks (q3w) per SoA.

Who can take part

Age range

18 Years and older

Sex

All (male and female)

Healthy volunteers

No - a diagnosis or condition is required

Phase

Phase 3

Study type

Interventional (participants receive a specific treatment)

Inclusion criteria

Age
Participant must be ≥ 18 years.
Type of Participant and Disease Characteristics
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.
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.
Participants must not have received prior EGFR TKIs or other systemic therapy for Stage IIIB, IIIC or IV NSCLC.
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.
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.
WHO performance status of 0 or 1.
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.
Adequate bone marrow reserve and organ function before the first dose of study intervention.

Exclusion criteria

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.
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.
History of another primary malignancy.
Spinal cord compression and/or unstable brain metastases.
Clinically significant corneal disease.
Has active or uncontrolled hepatitis B or C virus infection, as defined by Protocol.
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.
Has clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.

Where it is running

60 locations listed across 17 US states.

Research Site - Fountain Valley, California, United States
Research Site - Los Alamitos, California, United States
Research Site - Los Angeles, California, United States
Research Site - Los Angeles, California, United States
Research Site - Orange, California, United States
Research Site - San Diego, California, United States
Research Site - Santa Monica, California, United States
Research Site - Walnut Creek, California, United States
Research Site - New Haven, Connecticut, United States
Research Site - Washington D.C., District of Columbia, United States
Research Site - Jacksonville, Florida, United States
Research Site - Ocala, Florida, United States
Research Site - Orange City, Florida, United States
Research Site - Honolulu, Hawaii, United States
Research Site - Chicago, Illinois, United States
Research Site - Hinsdale, Illinois, United States
Research Site - North Chicago, Illinois, United States
Research Site - Fort Wayne, Indiana, United States
Research Site - Bethesda, Maryland, United States
Research Site - Detroit, Michigan, United States
Research Site - Saint Paul, Minnesota, United States
Research Site - Bridgeton, Missouri, United States
Research Site - St Louis, Missouri, United States
Research Site - Las Vegas, Nevada, United States
Research Site - Brooklyn, New York, United States
Research Site - New York, New York, United States
Research Site - Dallas, Texas, United States
Research Site - Houston, Texas, United States
Research Site - Houston, Texas, United States
Research Site - Webster, Texas, United States
Research Site - Woodway, Texas, United States
Research Site - Fairfax, Virginia, United States
Research Site - Fort Belvoir, Virginia, United States
Research Site - Midlothian, Virginia, United States
Research Site - Seattle, Washington, United States
Research Site - Tacoma, Washington, United States
Research Site - Milwaukee, Wisconsin, United States
Research Site - A Coruña, Spain
Research Site - Adapazarı, Turkey (Türkiye)
Research Site - Angers, France
Research Site - Ankara, Turkey (Türkiye)
Research Site - Bangalore, India
Research Site - Bangkok, Thailand
Research Site - Bangkok, Thailand
Research Site - Barcelona, Spain
Research Site - Barretos, Brazil
Research Site - Beijing, China
Research Site - Beijing, China
Research Site - Beijing, China
Research Site - Berlin, Germany
Research Site - Bystra, Poland
Research Site - Camperdown, Australia
Research Site - Changchun, China
Research Site - Changsha, China
Research Site - Chengdu, China
Research Site - Chengdu, China
Research Site - Chengdu, China
Research Site - Chongqing, China
Research Site - Chongqing, China
Research Site - Chūōku, Japan

Showing 60 of 167 listed sites. See the official record for the complete list.

Read the full protocol, contacts and eligibility on ClinicalTrials.gov →