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 - TROPION-Lung14

Study identifier:D516NC00001

ClinicalTrials.gov identifier:NCT06350097

EudraCT identifier:N/A

CTIS identifier:2023-509883-89-00

Recruiting

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

Medical condition

Non-small Cell Lung Cancer

Phase

Phase 3

Healthy volunteers

Study drug

Osimertinib, Datopotamab Deruxtecan

Sex

All

Estimated Enrollment

582

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 29 Apr 2024

Estimated Primary Completion Date: 21 Mar 2028

Estimated Study Completion Date: 25 May 2032

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2024 by AstraZeneca

Collaborators

Daiichi Sankyo

Inclusion and exclusion criteria

Inclusion Criteria

Age
1. Participant must be ≥ 18 years; Participant from Japan must be ≥ 20 years, at the time of signing the ICF.
Type of Participant and Disease Characteristics
2. Histologically or cytologically documented nonsquamous NSCLC.
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 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 EGFR mutations.
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 .
Sex and Contraceptive/Barrier Requirements
10. Male and female
Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Other Inclusion Criteria
11. All races, gender and ethnic groups are eligible for this study.

Exclusion Criteria

Medical Conditions
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.
5. Clinically significant corneal disease.
6. Has active or uncontrolled hepatitis B or C virus infection.
7. Known HIV infection that is not well controlled.
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.
10. Uncontrolled or significant cardiac disease.
11. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
12. Has severe pulmonary function compromise.
Prior/Concomitant Therapy
13. Prior exposure to any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase I, TROP2-targeted therapy.
Prior/Concurrent Clinical Study Experience
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.

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Arms	Assigned Interventions
Experimental: Arm 1: Osimertinib in combination with Datopotamab Deruxtecan Participants in this group will receive osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion q3w of Day 1 of every 21-day cycle.	Drug: Osimertinib Arm 1: Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion. Arm 2: Osimertinib 80 mg QD as oral tablet . Other Name: Osimertinib: AZD9291 Other Name: Datopotamab Deruxtecan: Dato-DXd Drug: Datopotamab Deruxtecan Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion. Other Name: Osimertinib: AZD9291 Other Name: Datopotamab Deruxtecan: Dato-DXd
Active Comparator: Arm 2: Osimertinib monotherapy Participants in this group will receive osimertinib 80 mg QD as oral tablet.	Drug: Osimertinib Arm 1: Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion. Arm 2: Osimertinib 80 mg QD as oral tablet . Other Name: Osimertinib: AZD9291 Other Name: Datopotamab Deruxtecan: Dato-DXd

Arms

Assigned Interventions

Experimental: Arm 1: Osimertinib in combination with Datopotamab Deruxtecan
Participants in this group will receive osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion q3w of Day 1 of every 21-day cycle.

Drug: Osimertinib
Arm 1: Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion. Arm 2: Osimertinib 80 mg QD as oral tablet .

Other Name: Osimertinib: AZD9291

Other Name: Datopotamab Deruxtecan: Dato-DXd

Drug: Datopotamab Deruxtecan
Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion.

Other Name: Osimertinib: AZD9291

Other Name: Datopotamab Deruxtecan: Dato-DXd

Active Comparator: Arm 2: Osimertinib monotherapy
Participants in this group will receive osimertinib 80 mg QD as oral tablet.

Drug: Osimertinib
Arm 1: Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion. Arm 2: Osimertinib 80 mg QD as oral tablet .

Other Name: Osimertinib: AZD9291

Other Name: Datopotamab Deruxtecan: Dato-DXd

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

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 - TROPION-Lung14

Official Title

Medical condition

Phase

Healthy volunteers

Study drug

Sex

Estimated Enrollment

Study type

Age

Date

Study design

Verification:

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Documents available

Trial Results Summaries

Contacts

Contact