RECRUITING

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

Conditions

Non-small Cell Lung Cancer Non-small Cell Lung Cancer, NSCLC, Epidermal Growth Factor Receptor (EGFR) Mutation-positive, Osimertinib, Dato-DXd, Datopotamab Deruxtecan, Tagrisso

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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 9 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.

Official Title

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

Quick Facts

Study Start:2024-04-29

Study Completion:2032-05-25

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06350097

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Participant must be ≥ 18 years. 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 within 7 days before the first dose of study intervention. 10. Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 11. All races, gender and ethnic groups are eligible for this study.	1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, psychiatric illness/social situations), history of allogenic organ transplant, and/or substance abuse 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 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. Known HIV infection that is not well controlled, as defined by Protocol. 8. Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible). 9. Resting ECG with clinically abnormal findings, as defined by Protocol. 10. Uncontrolled or significant cardiac disease, as defined by Protocol. 11. 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. 12. Pulmonary embolism within 3 months of the study enrolment or has severe pulmonary function compromise. 13. Prior exposure to any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase I, TROP2-targeted therapy. 14. Participants with a known history of severe hypersensitivity reactions to either Dato-DXd and osimertinib or any excipients of Dato DXd and osimertinib or drugs with a similar chemical structure or class to DXd and osimertinib.

Inclusion Criteria

Exclusion Criteria

1. Participant must be ≥ 18 years.
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 within 7 days before the first dose of study intervention.
10. Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
11. All races, gender and ethnic groups are eligible for this study.

1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, psychiatric illness/social situations), history of allogenic organ transplant, and/or substance abuse 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 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. Known HIV infection that is not well controlled, as defined by Protocol.
8. Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible).
9. Resting ECG with clinically abnormal findings, as defined by Protocol.
10. Uncontrolled or significant cardiac disease, as defined by Protocol.
11. 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.
12. Pulmonary embolism within 3 months of the study enrolment or has severe pulmonary function compromise.
13. Prior exposure to any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase I, TROP2-targeted therapy.
14. Participants with a known history of severe hypersensitivity reactions to either Dato-DXd and osimertinib or any excipients of Dato DXd and osimertinib or drugs with a similar chemical structure or class to DXd and osimertinib.

Contacts and Locations

Study Contact

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479

information.center@astrazeneca.com

Study Locations (Sites)

Research Site

Fountain Valley, California, 92708

United States

Research Site

Los Alamitos, California, 90720

United States

Research Site

Los Angeles, California, 90017

United States

Research Site

Los Angeles, California, 90033

United States

Research Site

Los Angeles, California, 90095

United States

Research Site

Orange, California, 92868

United States

Research Site

San Diego, California, 92123

United States

Research Site

Walnut Creek, California, 94598

United States

Research Site

New Haven, Connecticut, 06510

United States

Research Site

Washington, District of Columbia, 20037

United States

Research Site

Jacksonville, Florida, 32256

United States

Research Site

Ocala, Florida, 34474

United States

Research Site

Honolulu, Hawaii, 96819

United States

Research Site

North Chicago, Illinois, 60064

United States

Research Site

Fort Wayne, Indiana, 46845

United States

Research Site

Bethesda, Maryland, 20817

United States

Research Site

Detroit, Michigan, 48201

United States

Research Site

Saint Paul, Minnesota, 55102

United States

Research Site

Saint Louis, Missouri, 63110

United States

Research Site

New York, New York, 10065

United States

Research Site

Dallas, Texas, 75390

United States

Research Site

Houston, Texas, 77030

United States

Research Site

Houston, Texas, 77090

United States

Research Site

Webster, Texas, 77598

United States

Research Site

Woodway, Texas, 76712

United States

Research Site

Fairfax, Virginia, 22031

United States

Research Site

Fort Belvoir, Virginia, 22060

United States

Research Site

Midlothian, Virginia, 23114

United States

Research Site

Seattle, Washington, 98104

United States

Collaborators and Investigators

Sponsor: AstraZeneca

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-04-29

Study Completion Date2032-05-25

Study Record Updates

Study Start Date2024-04-29

Study Completion Date2032-05-25

Terms related to this study

Keywords Provided by Researchers

Non-small Cell Lung Cancer, NSCLC, Epidermal Growth Factor Receptor (EGFR) Mutation-positive, Osimertinib, Dato-DXd, Datopotamab Deruxtecan, Tagrisso

Additional Relevant MeSH Terms

Non-small Cell Lung Cancer