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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04612751




Registration number
NCT04612751
Ethics application status
Date submitted
21/10/2020
Date registered
3/11/2020

Titles & IDs
Public title
Phase 1b Study of Dato-DXd in Combination With Immunotherapy With or Without Carboplatin in Advanced or Metastatic Non-Small Cell Lung Cancer
Scientific title
A Phase 1b, Multicenter, 2-Part, Open-Label Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Immunotherapy With or Without Carboplatin in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (Tropion-Lung04)
Secondary ID [1] 0 0
2023-505992-54-00
Secondary ID [2] 0 0
D926FC00001
Universal Trial Number (UTN)
Trial acronym
TROPION-Lung04
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced or Metastatic NSCLC 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Datopotamab deruxtecan
Treatment: Drugs - Durvalumab
Treatment: Drugs - Carboplatin
Treatment: Drugs - AZD2936
Treatment: Drugs - MEDI5752
Treatment: Drugs - AZD7789

Experimental: Cohort 1 - Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy

Experimental: Cohort 2 - Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy

Experimental: Cohort 3 - Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy

Experimental: Cohort 4 - Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy

Experimental: Cohort 5 - Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC

Experimental: Cohort 6 - Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC

Experimental: Cohort 7 - Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC

Experimental: Cohort 8 - Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC

Experimental: Cohort 9 - Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC

Experimental: Cohort 10 - Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC

Experimental: Cohort 11 - Datopotamab deruxtecan (Dato-DXd) + MEDI5752 in participants with treatment-naïve NSCLC

Experimental: Cohort 12 - Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC

Experimental: Cohort 13 - Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC

Experimental: Cohort 14 - Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with treatment-naïve NSCLC

Experimental: Cohort 4A - Datopotamab deruxtecan (Dato-DXd) + Durvalumab + carboplatin in participants with treatment-naïve NSCLC


Treatment: Drugs: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle

Treatment: Drugs: Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle

Treatment: Drugs: Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle

Treatment: Drugs: AZD2936
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle

Treatment: Drugs: MEDI5752
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle

Treatment: Drugs: AZD7789
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with DLTs; TEAEs and other safety parameters during the study.
Timepoint [1] 0 0
DLTs: within first cycle (21 days); TEAEs and other safety parameters: when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up (approximately 60 months)
Secondary outcome [1] 0 0
ORR as assessed by investigator per RECIST Version 1.1
Timepoint [1] 0 0
At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Secondary outcome [2] 0 0
Duration of Response as assessed by investigator per RECIST version 1.1
Timepoint [2] 0 0
At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Secondary outcome [3] 0 0
Disease Control Rate as assessed by the investigator per RECIST version 1.1
Timepoint [3] 0 0
At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Secondary outcome [4] 0 0
Progression-free Survival as assessed by the investigator per RECIST v1.1
Timepoint [4] 0 0
At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Secondary outcome [5] 0 0
Time to Response as assessed by investigator per RECIST Version 1.1
Timepoint [5] 0 0
At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Secondary outcome [6] 0 0
Best percentage change in the Sum of Diameters of measurable tumors
Timepoint [6] 0 0
At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Secondary outcome [7] 0 0
Overall Survival
Timepoint [7] 0 0
At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Secondary outcome [8] 0 0
Pharmacokinetic Parameter Maximum Plasma/Serum Concentration (Cmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a. Serum concentrations of durvalumab and MEDI5752, AZD2936, MEDI5752 and AZD7789.
Timepoint [8] 0 0
At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Secondary outcome [9] 0 0
Pharmacokinetic Parameter Time to Maximum Plasma/Serum Concentration (Tmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a.
Timepoint [9] 0 0
At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Secondary outcome [10] 0 0
Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a.
Timepoint [10] 0 0
At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Secondary outcome [11] 0 0
Prevalence of Dato-Dxd, durvalumab, AZD2936, MEDI5752 and AZD7789 ADA
Timepoint [11] 0 0
At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Secondary outcome [12] 0 0
Incidence of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789 ADA
Timepoint [12] 0 0
At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).

Eligibility
Key inclusion criteria
* Participant =18 years old on the day of signing the ICF (local regulatory requirement to consent should be followed).
* Histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC, without EGFR or ALK genomic alterations (testing not required for participants with documented squamous histology) and no known genomic alterations in other actionable driver kinases with approved therapies. Participants whose tumors harbor KRAS mutations are eligible for this study.
* For Cohorts 1 to 4, participants must be treatment-naïve or have received and radiologically progressed after only 1 prior line of systemic chemotherapy, without concomitant immune checkpoint inhibitors for advanced or metastatic NSCLC. For Cohorts 4a, 5 to 11, and 14, participants must be treatment-naïve for advanced or metastatic NSCLC. For Cohorts 12 to 13, participants must be CPI acquired resistant after 1 or 2 prior lines of systemic therapy for advanced or metastatic NSCLC, of which 1 should have contained an approved anti-PD-1/PD L1. Cohort 4a will enroll participants whose tumors have squamous histology only; Cohorts 5 Part 2A and Part 2B as well as Cohorts 12 and 13 will enroll participants whose tumors have non-squamous histology only.
* Willing and able to undergo a mandatory tumor biopsy. A tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen may be substituted for the biopsy collected during screening. For Cohorts 12 and 13, a tumor sample taken =24 months prior to screening is acceptable.
* Has measurable disease per RECIST1.1 within 28 days prior to Cycle 1 Day 1
* Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1 at screening
* Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 day 1
* For Cohorts 5 to 14 only: Documented IHC PD-L1 expression per analytically validated Ventana PD-L1 (SP263) IHC assay, 22C3 PharmDx assay, or 28-8 PharmDx assay
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Active or prior documented autoimmune or inflammatory disorders
* Uncontrolled or significant cardiac disease
* History of another primary malignancy with exceptions
* active or uncontrolled hepatitis B or C virus or uncontrolled HIV infection
* spinal cord compression or clinically active CNS metastases
* History of (non-infectious) ILD/pneumonitis that required steroids
* Clinically severe pulmonary compromise resulting from intercurrent pulmonary illness
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
* Clinically significant corneal disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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 1
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
2/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/01/2026
Actual
Sample size
Target
371
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New Hampshire
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
Belgium
State/province [13] 0 0
Hasselt
Country [14] 0 0
Belgium
State/province [14] 0 0
Mechelen
Country [15] 0 0
Belgium
State/province [15] 0 0
Roeselare
Country [16] 0 0
France
State/province [16] 0 0
Paris Cedex 05
Country [17] 0 0
Italy
State/province [17] 0 0
Aviano
Country [18] 0 0
Italy
State/province [18] 0 0
Meldola
Country [19] 0 0
Italy
State/province [19] 0 0
Milano
Country [20] 0 0
Italy
State/province [20] 0 0
Orbassano
Country [21] 0 0
Italy
State/province [21] 0 0
Roma
Country [22] 0 0
Japan
State/province [22] 0 0
Koto-ku
Country [23] 0 0
Japan
State/province [23] 0 0
Sunto-gun
Country [24] 0 0
Japan
State/province [24] 0 0
Yokohama-shi
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Busan
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Cheongiu
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Hwasun-gun
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
JinJoo
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Seoul
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Suwon-si
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Suwon
Country [32] 0 0
Poland
State/province [32] 0 0
Gdansk
Country [33] 0 0
Poland
State/province [33] 0 0
Lublin
Country [34] 0 0
Poland
State/province [34] 0 0
Warszawa
Country [35] 0 0
Poland
State/province [35] 0 0
Lódz
Country [36] 0 0
Spain
State/province [36] 0 0
A Coruña
Country [37] 0 0
Spain
State/province [37] 0 0
Badalona
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Spain
State/province [40] 0 0
Pozuelo de Alarcon
Country [41] 0 0
Spain
State/province [41] 0 0
Sevilla
Country [42] 0 0
Taiwan
State/province [42] 0 0
Changhua
Country [43] 0 0
Taiwan
State/province [43] 0 0
Hsinchu
Country [44] 0 0
Taiwan
State/province [44] 0 0
Kaohsiung City
Country [45] 0 0
Taiwan
State/province [45] 0 0
Taichung
Country [46] 0 0
Taiwan
State/province [46] 0 0
Tainan
Country [47] 0 0
Taiwan
State/province [47] 0 0
Taipei City
Country [48] 0 0
Taiwan
State/province [48] 0 0
Taipei
Country [49] 0 0
Taiwan
State/province [49] 0 0
Taoyuan
Country [50] 0 0
Turkey
State/province [50] 0 0
Adana
Country [51] 0 0
Turkey
State/province [51] 0 0
Ankara
Country [52] 0 0
Turkey
State/province [52] 0 0
Istanbul
Country [53] 0 0
Turkey
State/province [53] 0 0
Izmir
Country [54] 0 0
Turkey
State/province [54] 0 0
Konya
Country [55] 0 0
Turkey
State/province [55] 0 0
Malatya

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
Trial website
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
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04612751