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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06350097




Registration number
NCT06350097
Ethics application status
Date submitted
2/04/2024
Date registered
5/04/2024
Date last updated
28/05/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
D516NC00001
Universal Trial Number (UTN)
Trial acronym
TROPION-Lung14
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Osimertinib
Treatment: Drugs - Datopotamab Deruxtecan

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.

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


Treatment: Drugs: 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 .

Treatment: Drugs: Datopotamab Deruxtecan
Osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS by BICR in all randomised participants.
Timepoint [1] 0 0
It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
Secondary outcome [1] 0 0
To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of OS in all randomised participants.
Timepoint [1] 0 0
It is anticipated that it will be performed approximately 7 years after the first participant has been randomised.
Secondary outcome [2] 0 0
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS on CNS metastases in participants with CNS metastases at baseline
Timepoint [2] 0 0
It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
Secondary outcome [3] 0 0
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS by investigator in all randomised participants.
Timepoint [3] 0 0
It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
Secondary outcome [4] 0 0
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of ORR in all randomised participants with measurable disease at baseline.
Timepoint [4] 0 0
It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
Secondary outcome [5] 0 0
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of DoR in all randomised participants with measurable disease at baseline.
Timepoint [5] 0 0
It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
Secondary outcome [6] 0 0
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib on the prevention of CNS metastases
Timepoint [6] 0 0
It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
Secondary outcome [7] 0 0
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS2 in all randomised participants
Timepoint [7] 0 0
It is anticipated that it will be performed approximately 7 years after the first participant has been randomised.
Secondary outcome [8] 0 0
To assess the PK of osimertinib and Datopotamab Deruxtecan
Timepoint [8] 0 0
It is anticipated that it will be performed approximately 7 years after the first participant has been randomised.
Secondary outcome [9] 0 0
To investigate the immunogenicity of Datopotamab Deruxtecan
Timepoint [9] 0 0
It is anticipated that it will be performed approximately 7 years after the first participant has been randomised.
Secondary outcome [10] 0 0
To compare the local EGFR mutation test result used for patient selection with the retrospective central cobas® EGFR Mutation Test v2 results from baseline tumour samples
Timepoint [10] 0 0
It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
Secondary outcome [11] 0 0
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan vs. osimertinib monotherapy based on the cobas® EGFR Mutation Test v2 plasma screening test result for Ex19del or L858R EGFR mutations
Timepoint [11] 0 0
It is anticipated that it will be performed approximately 7 years after the first participant has been randomised.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/04/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
25/05/2032
Actual
Sample size
Target
582
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Clayton
Recruitment hospital [2] 0 0
Research Site - Kogarah
Recruitment hospital [3] 0 0
Research Site - Westmead
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
China
State/province [1] 0 0
Changchun
Country [2] 0 0
China
State/province [2] 0 0
Chongqing
Country [3] 0 0
China
State/province [3] 0 0
Jinan
Country [4] 0 0
China
State/province [4] 0 0
Kunming
Country [5] 0 0
China
State/province [5] 0 0
Linhai
Country [6] 0 0
China
State/province [6] 0 0
Shanghai
Country [7] 0 0
Korea, Republic of
State/province [7] 0 0
Seoul
Country [8] 0 0
Taiwan
State/province [8] 0 0
Taipei City
Country [9] 0 0
Taiwan
State/province [9] 0 0
Taipei
Country [10] 0 0
Taiwan
State/province [10] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Daiichi Sankyo
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate efficacy and safety of osimertinib (tablet) in
combination with Datopotamab Deruxtecan (i.v. infusion) compared with osimertinib (tablet)
monotherapy as 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
Datopotamab Deruxtecan 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, IP discontinuation or primary PFS DCO. Participants who are
receiving osimertinib + Datopotamab Deruxtecan are still required to attend visit to perform
assessment every 3 weeks (q3w) per SoA.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06350097
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06350097