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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06467357




Registration number
NCT06467357
Ethics application status
Date submitted
21/05/2024
Date registered
21/06/2024

Titles & IDs
Public title
Phase 3 Study of T-DXd and Rilvegostomig Versus SoC in Advanced HER2-expressing Biliary Tract Cancer
Scientific title
DESTINY-Biliary Tract Cancer-01: A Phase 3 Study of Trastuzumab Deruxtecan (T-DXd) and Rilvegostomig Versus Standard-of-Care Gemcitabine, Cisplatin, and Durvalumab for First Line Locally Advanced or Metastatic HER2-expressing Biliary Tract Cancer
Secondary ID [1] 0 0
D781PC00001
Universal Trial Number (UTN)
Trial acronym
DESTINY-BTC01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Biliary Tract Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Cisplatin
Treatment: Drugs - Durvalumab
Treatment: Drugs - Trastuzumab deruxtecan
Treatment: Drugs - Rilvegostomig
Diagnosis / Prognosis - Agilent HercepTest™ mAb pharmDx
Diagnosis / Prognosis - Ventana PD-L1 SP263 assay

Experimental: Trastuzumab deruxtecan + rilvegostomig - Trastuzumab deruxtecan (T-DXd; DS-8201a) in combination with rilvegostomig arm

Experimental: Trastuzumab deruxtecan - Trastuzumab deruxtecan (T-DXd; DS-8201a) arm

Active comparator: Standard of Care - Gemcitabine and cisplatin in combination with durvalumab arm


Treatment: Drugs: Gemcitabine
Standard of care chemotherapy by intravenous infusion

Treatment: Drugs: Cisplatin
Standard of care chemotherapy by intravenous infusion

Treatment: Drugs: Durvalumab
Standard of care immunotherapy by intravenous infusion

Treatment: Drugs: Trastuzumab deruxtecan
Experimental therapy by intravenous infusion

Treatment: Drugs: Rilvegostomig
Experimental therapy by intravenous infusion

Diagnosis / Prognosis: Agilent HercepTest™ mAb pharmDx
A semi-quantitative immunohistochemical assay to determine HER2 overexpression in FFPE breast cancer tissues routinely processed for histological evaluation.

Based on a primary monoclonal rabbit antibody which visualises Her2 overexpression utilising a fully automated IHC platform (Dako Omnis).

Diagnosis / Prognosis: Ventana PD-L1 SP263 assay
A qualitative immunohistochemical assay to determine the level of PD-L1 expression in FFPE non-small cell lung cancer (NSCLC) tissues routinely processed for histological evaluation. Based on a rabbit monoclonal anti-PD-L1 clone SP263 which visualises PD-L1 protein using a VENTANA BenchMark ULTRA instrument
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Diagnosis / Prognosis
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety Run In: To evaluate the safety and tolerability of T-DXd with rilvegostomig
Timepoint [1] 0 0
Until all patients have completed at least 1 full Cycle (each cycle is 21 days)
Primary outcome [2] 0 0
Randomized Portion: To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care (SoC) in terms of Overall Survival in the HER2 IHC 3+ population
Timepoint [2] 0 0
From date of treatment assignment until the date of death from any cause (estimated to be assessed up to 48 months after first subject randomized)
Secondary outcome [1] 0 0
To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Overall Survival in the ITT population (HER2 IHC 3+/2+)
Timepoint [1] 0 0
From date of randomization until the date of death from any cause (estimated to be assessed up to 48 months after first subject randomized)
Secondary outcome [2] 0 0
To evaluate the efficacy of T-DXd monotherapy vs Standard of Care in terms of Overall Survival in the HER2 IHC 3+ population
Timepoint [2] 0 0
From date of randomization until the date of death from any cause (estimated to be assessed up to 48 months after first subject randomized)
Secondary outcome [3] 0 0
To evaluate the efficacy of T-DXd monotherapy vs Standard of Care in terms of Overall Survival in the ITT population
Timepoint [3] 0 0
From date of randomization until the date of death from any cause (estimated to be assessed up to 48 months after first subject randomized)
Secondary outcome [4] 0 0
To further evaluate efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Progression Free Survival in HER2 IHC 3+ and ITT populations
Timepoint [4] 0 0
From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first (estimated to be assessed up to 48 months)
Secondary outcome [5] 0 0
To further evaluate efficacy of T-DXd monotherapy vs Standard of Care in terms of Progression Free Survival in HER2 IHC 3+ and ITT populations
Timepoint [5] 0 0
From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first (estimated to be assessed up to 48 months)
Secondary outcome [6] 0 0
To further evaluate the efficacy of T-DXd with rilvegostomig vs Standrad of Care in terms of objective response rate in the HER2 IHC 3+ and ITT populations
Timepoint [6] 0 0
Estimated up to 6 months since randomization
Secondary outcome [7] 0 0
To further evaluate the efficacy of T-DXd monotherapy vs Standrad of Care in terms of objective response rate in the HER2 IHC 3+ and ITT populations
Timepoint [7] 0 0
Estimated up to 6 months since randomization
Secondary outcome [8] 0 0
To further evaluate efficacy of T-DXd with rilvegostomig vs Standard if Care in terms of duration of response in patients with HER2-expressing BTC in the IHC 3+ and ITT populations
Timepoint [8] 0 0
From the date of first documented response until date of documented progression or death due to any cause, whichever occurs first (estimated up to 48 months)
Secondary outcome [9] 0 0
To further evaluate efficacy of T-DXd monotherapy vs Standard if Care in terms of duration of response in patients with HER2-expressing BTC in the IHC 3+ and ITT populations
Timepoint [9] 0 0
From the date of first documented response until date of documented progression or death due to any cause, whichever occurs first (estimated up to 48 months)
Secondary outcome [10] 0 0
To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of Overall survival in HER2 IHC 3+ and ITT populations.
Timepoint [10] 0 0
From the date of randomisation until progression or death due to any cause, whichever occurs first (estimated up to 48 months)
Secondary outcome [11] 0 0
To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of PFS in HER2 IHC 3+ and ITT populations.
Timepoint [11] 0 0
From the date of randomisation until progression or death due to any cause, whichever occurs first (estimated up to 48 months)
Secondary outcome [12] 0 0
To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of Duration of response in HER2 IHC 3+ and ITT populations.
Timepoint [12] 0 0
From the date of first response until progression or death due to any cause, whichever occurs first (estimated up to 48 months)
Secondary outcome [13] 0 0
To further evaluate the efficacy of T-DXd with rilvegostomig versus T-DXd monotherapy in terms of Objective response rate in HER2 IHC 3+ and ITT populations.
Timepoint [13] 0 0
Estimated up to 6 months
Secondary outcome [14] 0 0
To assess the safety and tolerability of T-DXd with rilvegostomig vs Standard of Care
Timepoint [14] 0 0
From first dose of study intervention until 90 days after the last dose except for ILD/pneumonitis, where safety follow-up will be continued until resolution.
Secondary outcome [15] 0 0
To assess the safety and tolerability of T-DXd monotherapy vs Standard of Care
Timepoint [15] 0 0
From first dose of study intervention until 90 days after the last dose except for ILD/pneumonitis, where safety follow-up will be continued until resolution.
Secondary outcome [16] 0 0
To describe patient-reported tolerability of T-DXd with rilvegostomig in comparison to Standard of Care based on a summary of symptomatic AEs
Timepoint [16] 0 0
Until End of Study (estimated up to 48 months)
Secondary outcome [17] 0 0
To describe patient-reported tolerability of T-DXd monotherapy in comparison to SoC based on a summary of symptomatic AEs
Timepoint [17] 0 0
Until End of Study (estimated up to 48 months)
Secondary outcome [18] 0 0
To describe patient-reported tolerability of T-DXd with rilvegostomig in comparison to T-DXd monotherapy based on a summary of symptomatic AEs and overall side-effect bother
Timepoint [18] 0 0
Until End of Study (estimated up to 48 months)
Secondary outcome [19] 0 0
To assess time to deterioration in physical functioning in patients treated with T-DXd with rilvegostomig vs Standard of Care
Timepoint [19] 0 0
Until End of Study (estimated up to 48 months)
Secondary outcome [20] 0 0
To assess time to deterioration in physical functioning in patients treated with T-DXd monotherapy vs Standard of care
Timepoint [20] 0 0
Until End of Study (estimated up to 48 months)
Secondary outcome [21] 0 0
To assess time to deterioration in physical functioning in patients treated with T-DXd with rilvegostomig vs T-DXd monotherapy
Timepoint [21] 0 0
Until End of Study (estimated up to 48 months)
Secondary outcome [22] 0 0
To assess the pharmacokinetics of T-DXd, total anti- HER2 antibody, DXd and rilvegostomig in serum
Timepoint [22] 0 0
From the time of informed consent until 30 and 90 days after the last dose of T-DXd and rilvegostomig, respectively
Secondary outcome [23] 0 0
To investigate the immunogenicity of T-DXd and of rilvegostomig
Timepoint [23] 0 0
From the time of informed consent until 30 and 90 days after the last dose of T-DXd and rilvegostomig, respectively
Secondary outcome [24] 0 0
To describe patient-reported tolerability of T-DXd with rilvegostomig in comparison to Standard of Care based on overall side-effect bother
Timepoint [24] 0 0
Until End of Study (estimated up to 48 months)
Secondary outcome [25] 0 0
To describe patient-reported tolerability of T-DXd monotherapy in comparison to SoC based on overall side-effect bother
Timepoint [25] 0 0
Until End of Study (estimated up to 48 months)

Eligibility
Key inclusion criteria
Key

* Participants must be = 18 years of age at the time of screening. Other age restrictions may apply as per local regulations;
* Male and female;
* Unresectable, previously untreated, locally advanced or metastatic BTC. Prior treatment in the perioperative and/or adjuvant setting is permissible provided there is > 6 months (180 days) between the end of adjuvant treatment and the diagnosis of locally advanced or metastatic disease.
* histologically confirmed HER2-expressing (IHC 3+ or IHC 2+) BTC;
* Provision of FFPE tumor sample that is no older than 3 years;
* At least one target lesion assessed by the Investigator based on RECIST v1.1 (randomized portion only);
* WHO/ECOG performance status of 0 or 1;
* Adequate organ and bone marrow function within 14 days before randomization;
* Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential;

Key
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior exposure to other HER2 targeting therapies, ADCs, immune checkpoint inhibitors and therapeutic anticancer vaccines;
* histologically confirmed ampullary carcinoma;
* history of substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions;
* spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms;
* medical history of myocardial infarction within 6 months before randomization/enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV), unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event including stroke;
* Serious chronic gastrointestinal conditions associated with diarrhea (eg, active inflammatory bowel disease); active non-infectious skin disease (including any grade rash, urticaria, dermatitis, ulceration, or psoriasis) requiring systemic treatment;
* active autoimmune, connective tissue or inflammatory disorders that has required systemic treatment in the past 2 years, or where there is documented, or a suspicion of pulmonary involvement at the time of screening;
* Corrected QT interval (QTcF) prolongation to > 470 msec (females) or > 450 msec (males) based on average of the screening triplicate 12-lead ECG;
* History of (non-infectious) ILD/pneumonitis, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening;
* Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder;
* Prior pneumonectomy (complete);
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals;
* Active primary immunodeficiency, known uncontrolled active HIV infection or HCV;
* Pregnant or breastfeeding female patients, or patients who are planning to become pregnant;
* Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 6 months prior to randomization, or concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study (only randomized portion).

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
12/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
16/05/2029
Actual
Sample size
Target
620
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 - Nedlands
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New Mexico
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
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
Austria
State/province [13] 0 0
Linz
Country [14] 0 0
Austria
State/province [14] 0 0
Salzburg
Country [15] 0 0
Austria
State/province [15] 0 0
Wiener Neustadt
Country [16] 0 0
Austria
State/province [16] 0 0
Wien
Country [17] 0 0
Belgium
State/province [17] 0 0
Anderlecht
Country [18] 0 0
Belgium
State/province [18] 0 0
Edegem
Country [19] 0 0
Belgium
State/province [19] 0 0
Leuven
Country [20] 0 0
Belgium
State/province [20] 0 0
Liège
Country [21] 0 0
Belgium
State/province [21] 0 0
Roeselare
Country [22] 0 0
Brazil
State/province [22] 0 0
Porto Alegre
Country [23] 0 0
Brazil
State/province [23] 0 0
Sao Paulo
Country [24] 0 0
Canada
State/province [24] 0 0
Alberta
Country [25] 0 0
Canada
State/province [25] 0 0
Nova Scotia
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
Czechia
State/province [28] 0 0
Brno
Country [29] 0 0
Czechia
State/province [29] 0 0
Hradec Kralove
Country [30] 0 0
Czechia
State/province [30] 0 0
Olomouc
Country [31] 0 0
Czechia
State/province [31] 0 0
Praha 10
Country [32] 0 0
Czechia
State/province [32] 0 0
Praha 5
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Germany
State/province [34] 0 0
Dresden
Country [35] 0 0
Germany
State/province [35] 0 0
Frankfurt
Country [36] 0 0
Germany
State/province [36] 0 0
Freiburg
Country [37] 0 0
Germany
State/province [37] 0 0
Göttingen
Country [38] 0 0
Germany
State/province [38] 0 0
Hamburg
Country [39] 0 0
Germany
State/province [39] 0 0
Köln
Country [40] 0 0
Germany
State/province [40] 0 0
Leipzig
Country [41] 0 0
Germany
State/province [41] 0 0
Lübeck
Country [42] 0 0
Germany
State/province [42] 0 0
Munchen
Country [43] 0 0
Germany
State/province [43] 0 0
Ulm
Country [44] 0 0
Germany
State/province [44] 0 0
Wuerzburg
Country [45] 0 0
Italy
State/province [45] 0 0
Firenze
Country [46] 0 0
Italy
State/province [46] 0 0
Milano
Country [47] 0 0
Italy
State/province [47] 0 0
Naples
Country [48] 0 0
Italy
State/province [48] 0 0
Napoli
Country [49] 0 0
Italy
State/province [49] 0 0
Padova
Country [50] 0 0
Italy
State/province [50] 0 0
Rozzano
Country [51] 0 0
Italy
State/province [51] 0 0
Tricase
Country [52] 0 0
Japan
State/province [52] 0 0
Kashiwa
Country [53] 0 0
Japan
State/province [53] 0 0
Koto-ku
Country [54] 0 0
Japan
State/province [54] 0 0
Osaka-shi
Country [55] 0 0
Japan
State/province [55] 0 0
Suita-city
Country [56] 0 0
Japan
State/province [56] 0 0
Yokohama-shi
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Seoul
Country [58] 0 0
Malaysia
State/province [58] 0 0
George Town
Country [59] 0 0
Malaysia
State/province [59] 0 0
Johor Bahru
Country [60] 0 0
Malaysia
State/province [60] 0 0
Kuala Lumpur
Country [61] 0 0
Malaysia
State/province [61] 0 0
Kuching
Country [62] 0 0
Netherlands
State/province [62] 0 0
Rotterdam
Country [63] 0 0
Slovakia
State/province [63] 0 0
Banska Bystrica
Country [64] 0 0
Slovakia
State/province [64] 0 0
Bratislava
Country [65] 0 0
Slovakia
State/province [65] 0 0
Kosice
Country [66] 0 0
Slovakia
State/province [66] 0 0
Martin
Country [67] 0 0
Slovakia
State/province [67] 0 0
Trnava
Country [68] 0 0
Spain
State/province [68] 0 0
Barcelona
Country [69] 0 0
Spain
State/province [69] 0 0
Madrid
Country [70] 0 0
Spain
State/province [70] 0 0
Málaga
Country [71] 0 0
Taiwan
State/province [71] 0 0
Kaohsiung
Country [72] 0 0
Taiwan
State/province [72] 0 0
Taipei
Country [73] 0 0
Taiwan
State/province [73] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo
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
information.center@astrazeneca.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


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/NCT06467357