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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/NCT04612751




Registration number
NCT04612751
Ethics application status
Date submitted
21/10/2020
Date registered
3/11/2020
Date last updated
18/08/2023

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
2021-000274-28
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

Experimental: Cohort 1 - Datopotamab deruxtecan (Dato-DXd) + Durvalumab

Experimental: Cohort 2 - Datopotamab deruxtecan (Dato-DXd) + Durvalumab

Experimental: Cohort 3 - Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin

Experimental: Cohort 4 - Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin

Experimental: Cohort 5 - Datopotamab deruxtecan (Dato-DXd) + AZD2936

Experimental: Cohort 6 - Datopotamab deruxtecan (Dato-DXd) + AZD2936

Experimental: Cohort 7 - Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin

Experimental: Cohort 8 - Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin

Experimental: Cohort 9 - Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin

Experimental: Cohort 10 - Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin

Experimental: Cohort 11 - Datopotamab deruxtecan (Dato-DXd) + MEDI5752


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

Treatment: Drugs: MEDI5752
Intravenous infusion prior to Dato-DXd
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 55 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 55 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 55 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 55 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 55 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 55 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 55 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 55 months).
Secondary outcome [8] 0 0
Pharmacokinetic Parameter Maximum Plasma/Serum Concentration (Cmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a and AZD2936. Serum concentrations of durvalumab and MEDI5752.
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 55 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 and AZD2936. Serum concentrations of durvalumab and MEDI5752.
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 55 months).
Secondary outcome [10] 0 0
Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, AZD2936, Total anti-TROP2 antibody, and MAAA-1181a (Dose Escalation and Dose Expansion)
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 55 months).
Secondary outcome [11] 0 0
Prevalence of Dato-Dxd, durvalumab, AZD2936 and MEDI5752
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 55 months).
Secondary outcome [12] 0 0
Incidence of Dato-DXd, durvalumab, AZD2936 and MEDI5752 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 55 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 and no known genomic alterations in other
actionable driver kinases with approved therapies

- 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
5 to 11, participants must be treatment-naïve for advanced or metastatic NSCLC.

- Willing and able to undergo a mandatory tumor biopsy

- 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 11 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

- 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
232
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
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New Hampshire
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
Belgium
State/province [14] 0 0
Hasselt
Country [15] 0 0
Belgium
State/province [15] 0 0
Mechelen
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
Poland
Country [34] 0 0
Poland
State/province [34] 0 0
Lódz
Country [35] 0 0
Spain
State/province [35] 0 0
A Coruña
Country [36] 0 0
Spain
State/province [36] 0 0
Badalona
Country [37] 0 0
Spain
State/province [37] 0 0
Barcelona
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid
Country [39] 0 0
Spain
State/province [39] 0 0
Pozuelo de Alarcon
Country [40] 0 0
Spain
State/province [40] 0 0
Sevilla
Country [41] 0 0
Taiwan
State/province [41] 0 0
Changhua
Country [42] 0 0
Taiwan
State/province [42] 0 0
Hsinchu
Country [43] 0 0
Taiwan
State/province [43] 0 0
Kaohsiung City
Country [44] 0 0
Taiwan
State/province [44] 0 0
Taichung
Country [45] 0 0
Taiwan
State/province [45] 0 0
Tainan
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taipei City
Country [47] 0 0
Taiwan
State/province [47] 0 0
Taipei
Country [48] 0 0
Taiwan
State/province [48] 0 0
Taoyuan
Country [49] 0 0
Turkey
State/province [49] 0 0
Adana
Country [50] 0 0
Turkey
State/province [50] 0 0
Ankara
Country [51] 0 0
Turkey
State/province [51] 0 0
Istanbul
Country [52] 0 0
Turkey
State/province [52] 0 0
Izmir
Country [53] 0 0
Turkey
State/province [53] 0 0
Konya
Country [54] 0 0
Turkey
State/province [54] 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, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will assess safety, tolerability, and treatment activity of datopotamab deruxtecan
(Dato-DXd) in combination with immunotherapy in participants with advanced or metastatic
non-small cell lung cancer (NSCLC).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04612751
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04612751