Phase 3 Study of T-DXd and Rilvegostomig Versus SoC in Advanced HER2-expressing Biliary Tract Cancer
DESTINY-BTC01
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
2 other identifiers
interventional
620
26 countries
261
Brief Summary
The purpose of this study is to measure the efficacy and safety of T-DXd with rilvegostomig or T-DXd monotherapy compared with gemcitabine plus cisplatin and durvalumab in patients with advanced treatment naïve HER2-expressing BTC.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Aug 2024
Longer than P75 for phase_3
261 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 21, 2024
CompletedFirst Posted
Study publicly available on registry
June 21, 2024
CompletedStudy Start
First participant enrolled
August 12, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 12, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 16, 2029
April 16, 2026
April 1, 2026
3.8 years
May 21, 2024
April 15, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Safety Run In: To evaluate the safety and tolerability of T-DXd with rilvegostomig
Safety and tolerability will be evaluated by the proportion of treated patients with occurrence of AEs, SAEs and AESIs, as assessed by CTCAE v5.0.
Until all patients have completed at least 1 full Cycle (each cycle is 21 days)
Randomized Portion: To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care (SoC) in terms of Overall Survival in the FAS (HER2 IHC 3+) population
Overall survival (OS) in FAS (HER2 IHC 3+) population OS is defined as time from randomization date until the date of death due to any cause. The comparison will include all randomized patients, regardless of whether the patient withdraws from therapy or receives another anticancer therapy. The measure of interest is the hazard ratio of OS.
From date of treatment randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized)
Secondary Outcomes (27)
To evaluate the efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+/2+) population
From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized)
To evaluate the efficacy of T-DXd monotherapy vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+) population
From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized)
To evaluate the efficacy of T-DXd monotherapy vs Standard of Care in terms of Overall Survival in the FAS (HER2 IHC 3+/2+) population
From date of randomization until the date of death from any cause (estimated to be assessed up to 50 months after first subject randomized)
To further evaluate efficacy of T-DXd with rilvegostomig vs Standard of Care in terms of Progression Free Survival in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations
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 50 months)
To further evaluate efficacy of T-DXd monotherapy vs Standard of Care in terms of Progression Free Survival in FAS (HER2 IHC 3+) and FAS (HER2 IHC 3+/2+) populations
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 50 months)
- +22 more secondary outcomes
Study Arms (3)
Trastuzumab deruxtecan + rilvegostomig
EXPERIMENTALTrastuzumab deruxtecan (T-DXd; DS-8201a) in combination with rilvegostomig arm
Trastuzumab deruxtecan
EXPERIMENTALTrastuzumab deruxtecan (T-DXd; DS-8201a) arm
Standard of Care
ACTIVE COMPARATORGemcitabine and cisplatin in combination with durvalumab arm
Interventions
Experimental therapy by intravenous infusion
Eligibility Criteria
You may qualify if:
- Male and female patients must be at least 18 years of age at the time of signing the informed consent. Other age restrictions may apply as per local regulations.
- Unresectable, previously untreated, locally advanced or metastatic biliary tract adenocarcinoma. Prior treatment in the perioperative and/or adjuvant setting is permissible provided there is \> 3 months (90 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.
- Patients must provide an FFPE tumor sample that is no older than 3 years for tissue-based IHC staining to centrally determine HER2 expression, PD-L1 status, and other correlatives.
- Has 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 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
- 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.
- Minimum life expectancy of 12 weeks.
You may not qualify if:
- Prior exposure to other HER2 targeting therapies, ADCs, immune checkpoint inhibitors and therapeutic anticancer vaccines.
- Histologically confirmed ampullary carcinoma.
- Any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the Investigator, interfere with the patient's participation in the clinical study or evaluation of the clinical study results.
- 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 (eg, pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion etc).
- Prior pneumonectomy (complete).
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. Patients with prior cholangitis/biliary tract infections/biliary intervention (eg, stent, external drain) should have completed a full course of antibiotics prior to randomization.
- Active primary immunodeficiency, known uncontrolled active HIV infection or HCV.
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected nonmelanoma skin cancer and curatively treated in situ disease. For certain participant populations, exceptions could also include carcinomas in-situ or Ta tumors treated with curative intent.
- Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (Drainage and Cell free and Concentrated Ascites Reinfusion Therapy are not allowed within 2 weeks prior to screening assessment).
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (266)
Research Site
Scottsdale, Arizona, 85259, United States
Research Site
Tucson, Arizona, 85704, United States
Research Site
Tucson, Arizona, 85719, United States
Research Site
Fullerton, California, 92835, United States
Research Site
La Jolla, California, 92093, United States
Research Site
Los Alamitos, California, 90720, United States
Research Site
Los Angeles, California, 90017, United States
Research Site
Los Angeles, California, 90089, United States
Research Site
San Francisco, California, 94143, United States
Research Site
Walnut Creek, California, 94598, United States
Research Site
Washington D.C., District of Columbia, 20007, United States
Research Site
Fort Myers, Florida, 33901, United States
Research Site
Jacksonville, Florida, 32224, United States
Research Site
St. Petersburg, Florida, 33705, United States
Research Site
Tampa, Florida, 33606, United States
Research Site
West Palm Beach, Florida, 33401, United States
Research Site
Atlanta, Georgia, 30309, United States
Research Site
Coeur d'Alene, Idaho, 83814, United States
Research Site
Chicago, Illinois, 60612, United States
Research Site
Niles, Illinois, 60714, United States
Research Site
Towson, Maryland, 21204, United States
Research Site
Worcester, Massachusetts, 01655, United States
Research Site
Detroit, Michigan, 48202, United States
Research Site
Grand Rapids, Michigan, 49503, United States
Research Site
Rochester, Minnesota, 55905, United States
Research Site
Kansas City, Missouri, 64132, United States
Research Site
St Louis, Missouri, 63110, United States
Research Site
Albuquerque, New Mexico, 87102, United States
Research Site
New York, New York, 10032, United States
Research Site
White Plains, New York, 10601, United States
Research Site
Cleveland, Ohio, 44111, United States
Research Site
Cleveland, Ohio, 44124, United States
Research Site
Cleveland, Ohio, 44195, United States
Research Site
Columbus, Ohio, 43210, United States
Research Site
Pittsburgh, Pennsylvania, 15232, United States
Research Site
Greenville, South Carolina, 29605, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Austin, Texas, 78705, United States
Research Site
Dallas, Texas, 75246, United States
Research Site
Fort Worth, Texas, 76104, United States
Research Site
Fort Worth, Texas, 76104, United States
Research Site
Houston, Texas, 77030, United States
Research Site
Pearland, Texas, 77584, United States
Research Site
San Antonio, Texas, 78217, United States
Research Site
San Antonio, Texas, 78258, United States
Research Site
Fairfax, Virginia, 22031, United States
Research Site
Chermside, 4032, Australia
Research Site
Clayton, 3168, Australia
Research Site
Concord, 2139, Australia
Research Site
Nedlands, 6009, Australia
Research Site
Graz, 8036, Austria
Research Site
Linz, 4010, Austria
Research Site
Salzburg, 5020, Austria
Research Site
Vienna, 1090, Austria
Research Site
Wiener Neustadt, 2700, Austria
Research Site
Anderlecht, 1070, Belgium
Research Site
Edegem, 2650, Belgium
Research Site
Ghent, 9000, Belgium
Research Site
Leuven, 3000, Belgium
Research Site
Liège, 4000, Belgium
Research Site
Roeselare, 8800, Belgium
Research Site
Natal, 59012-300, Brazil
Research Site
Porto Alegre, 90035-000, Brazil
Research Site
Porto Alegre, 91350-200, Brazil
Research Site
Santa Maria, 97015-450, Brazil
Research Site
São Paulo, 01246-000, Brazil
Research Site
São Paulo, 05651-901, Brazil
Research Site
Vitória, 29043-272, Brazil
Research Site
Edmonton, Alberta, T6G 1Z2, Canada
Research Site
Halifax, Nova Scotia, B3H 1V7, Canada
Research Site
Brampton, Ontario, L6R 3J7, Canada
Research Site
Toronto, Ontario, M5G 2M9, Canada
Research Site
Montreal, Quebec, H3A 1A1, Canada
Research Site
Beijing, 100020, China
Research Site
Beijing, 100021, China
Research Site
Beijing, 100034, China
Research Site
Beijing, 100142, China
Research Site
Beijing, China
Research Site
Bengbu, 233004, China
Research Site
Changchun, 130021, China
Research Site
Changde, 415000, China
Research Site
Changsha, 410013, China
Research Site
Chengdu, 610041, China
Research Site
Chengdu, 610078, China
Research Site
Chongqing, 400030, China
Research Site
Fuzhou, 350007, China
Research Site
Guangzhou, 510080, China
Research Site
Guangzhou, 510515, China
Research Site
Guiyang, 550044, China
Research Site
Hangzhou, 310016, China
Research Site
Harbin, 150081, China
Research Site
Hefei, 230001, China
Research Site
Hefei, 230601, China
Research Site
Jinan, 250117, China
Research Site
Kunming, 650101, China
Research Site
Linyi, 276000, China
Research Site
Luoyang, 471000, China
Research Site
Nanchang, 330029, China
Research Site
Nanjing, 2100008, China
Research Site
Nanning, 530021, China
Research Site
Nantong, 226001, China
Research Site
Shanghai, 200001, China
Research Site
Shanghai, 201107, China
Research Site
Shanghai, 201114, China
Research Site
Shenyang, 110004, China
Research Site
Shenzhen, 518116, China
Research Site
Tianjin, 300060, China
Research Site
Weifang, 261000, China
Research Site
Wenzhou, 325035, China
Research Site
Wuhan, 430079, China
Research Site
Xi'an, 710061, China
Research Site
Zhengzhou, 450008, China
Research Site
Zhengzhou, 450052, China
Research Site
Brno, 625 00, Czechia
Research Site
Brno, 656 53, Czechia
Research Site
Hradec Králové, 500 05, Czechia
Research Site
Olomouc, 77900, Czechia
Research Site
Prague, 100 34, Czechia
Research Site
Prague, 15006, Czechia
Research Site
Brest, 29609, France
Research Site
Clichy, 92118, France
Research Site
Dijon, 21079, France
Research Site
Lille, 59037, France
Research Site
Lyon, 69008, France
Research Site
Lyon, 69373, France
Research Site
Marseille, 13008, France
Research Site
Montpellier, 34295, France
Research Site
Pessac, 33604, France
Research Site
Villejuif, 94800, France
Research Site
Berlin, 13353, Germany
Research Site
Bonn, 53127, Germany
Research Site
Cologne, 50937, Germany
Research Site
Dresden, 01370, Germany
Research Site
Frankfurt, 60488, Germany
Research Site
Freiburg im Breisgau, 79106, Germany
Research Site
Göttingen, 37075, Germany
Research Site
Hamburg, 22763, Germany
Research Site
Leipzig, 4103, Germany
Research Site
Lübeck, 23538, Germany
Research Site
München, 81377, DE, Germany
Research Site
Ulm, 89081, Germany
Research Site
Würzburg, 97080, Germany
Research Site
Hong Kong, 999077, Hong Kong
Research Site
Shatin, 00000, Hong Kong
Research Site
Dehradun, 248016, India
Research Site
Delhi, 110029, India
Research Site
Delhi, 110088, India
Research Site
Kanpur, 208001, India
Research Site
Kolkata, 700054, India
Research Site
Kolkata, 700094, India
Research Site
Mumbai, 400012, India
Research Site
Vadodara, 391760, India
Research Site
Varanasi, 221005, India
Research Site
Florence, 50134, Italy
Research Site
Milan, 20132, Italy
Research Site
Milan, 20162, Italy
Research Site
Naples, 80128, Italy
Research Site
Naples, 80131, Italy
Research Site
Padova, 35128, Italy
Research Site
Roma, 00133, Italy
Research Site
Rozzano, 20089, Italy
Research Site
Tricase, 73039, Italy
Research Site
Bunkyō City, 113-8431, Japan
Research Site
Bunkyō City, 113-8603, Japan
Research Site
Bunkyō City, 113-8677, Japan
Research Site
Chiba, 260-0877, Japan
Research Site
Fukuyama-shi, 721-8511, Japan
Research Site
Hirakata-shi, 573-1191, Japan
Research Site
Hiroshima, 734-8551, Japan
Research Site
Kanazawa, 920-8641, Japan
Research Site
Kashiwa, 227-8577, Japan
Research Site
Kawasaki-shi, 216-8511, Japan
Research Site
Kita-gun, 761-0793, Japan
Research Site
Kitaadachi-gun, 362-0806, Japan
Research Site
Kōtoku, 135-8550, Japan
Research Site
Kumamoto, 860-8556, Japan
Research Site
Kyoto, 606-8507, Japan
Research Site
Maebashi, 371-8511, Japan
Research Site
Mitaka-shi, 181-8611, Japan
Research Site
Nagoya, 464-8681, Japan
Research Site
Nagoya, 466-8560, Japan
Research Site
Osaka, 541-8567, Japan
Research Site
Osaka, 545-8586, Japan
Research Site
Sakaishi, 591-8025, Japan
Research Site
Sapporo, 060-8543, Japan
Research Site
Sendai, 980-8574, Japan
Research Site
Shinjuku-ku, 160-8582, Japan
Research Site
Suita, 565-0871, Japan
Research Site
Sunto-gun, 411-8777, Japan
Research Site
Ube-shi, 755-8505, Japan
Research Site
Wakayama, 641-8510, Japan
Research Site
Yokohama, 241-8515, Japan
Research Site
George Town, 10990, Malaysia
Research Site
Johor Bahru, 81100, Malaysia
Research Site
Kuala Lumpur, 50586, Malaysia
Research Site
Kuala Lumpur, 59100, Malaysia
Research Site
Kuching, 93586, Malaysia
Research Site
Rotterdam, 3015 GD, Netherlands
Research Site
Cebu City, 6000, Philippines
Research Site
Makati, 1229, Philippines
Research Site
Pasig, 1605, Philippines
Research Site
Quezon City, 1112, Philippines
Research Site
Bialystok, 15-027, Poland
Research Site
Katowice, 40-514, Poland
Research Site
Krakow, 31-501, Poland
Research Site
Lublin, 20-080, Poland
Research Site
Warsaw, 02-034, Poland
Research Site
Wroclaw, 50-556, Poland
Research Site
Dammam, 31444, Saudi Arabia
Research Site
Riyadh, 11426, Saudi Arabia
Research Site
Riyadh, 11525, Saudi Arabia
Research Site
Riyadh, 12713, Saudi Arabia
Research Site
Banská Bystrica, 974 01, Slovakia
Research Site
Bratislava, 833 10, Slovakia
Research Site
Košice, 041 91, Slovakia
Research Site
Martin, 036 59, Slovakia
Research Site
Trnava, 917 75, Slovakia
Research Site
Busan, 48108, South Korea
Research Site
Gyeonggi-do, 13620, South Korea
Research Site
Hwasun-gun, 58128, South Korea
Research Site
Seongnam-si, 13496, South Korea
Research Site
Seoul, 03080, South Korea
Research Site
Seoul, 05505, South Korea
Research Site
Seoul, 06351, South Korea
Research Site
Seoul, 06591, South Korea
Research Site
Seoul, 120-752, South Korea
Research Site
Barcelona, 08035, Spain
Research Site
Madrid, 28007, Spain
Research Site
Madrid, 28040, Spain
Research Site
Madrid, 28041, Spain
Research Site
Málaga, 29010, Spain
Research Site
Santander, 39008, Spain
Research Site
Kaohsiung City, 00807, Taiwan
Research Site
Kaohsiung City, 82445, Taiwan
Research Site
Kaohsiung City, 833, Taiwan
Research Site
Taichung, 40447, Taiwan
Research Site
Taichung, 407219, Taiwan
Research Site
Taipei, 10002, Taiwan
Research Site
Taipei, Taiwan
Research Site
Taoyuan District, 333, Taiwan
Research Site
Bangkok, 10400, Thailand
Research Site
Hat Yai, 90110, Thailand
Research Site
Khon Kaen, 40002, Thailand
Research Site
Muang, 50200, Thailand
Research Site
Mueang, 47000, Thailand
Research Site
Naimuang, 30000, Thailand
Research Site
Ongkharak, 26120, Thailand
Research Site
Si Sa Ket, 33000, Thailand
Research Site
Altındağ, 06230, Turkey (Türkiye)
Research Site
Antalya, 07100, Turkey (Türkiye)
Research Site
Istanbul, 34218, Turkey (Türkiye)
Research Site
Izmir, 35340, Turkey (Türkiye)
Research Site
Mezitli, 33200, Turkey (Türkiye)
Research Site
Yakutiye, 25040, Turkey (Türkiye)
Research Site
Birmingham, B15 2GW, United Kingdom
Research Site
Dundee, DD1 9SY, United Kingdom
Research Site
Glasgow, G12 0YN, United Kingdom
Research Site
Greater London, SW3 6JJ, United Kingdom
Research Site
Leeds, LS9 7TF, United Kingdom
Research Site
London, EC1A 7BE, United Kingdom
Research Site
Hanoi, 100000, Vietnam
Research Site
Ho Chi Minh City, 700000, Vietnam
Research Site
Ho Chi Minh City, 700000, Vietnam
Research Site
Ho Chi Minh City, 70000, Vietnam
Research Site
Ho Chi Minh City, 70000, Vietnam
Research Site
Vinh, 460000, Vietnam
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- This is an open-label, Sponsor-blinded study. To maintain the integrity of the study, Sponsor personnel directly involved in study conduct will not undertake or have access to efficacy data aggregated by treatment group prior to final data readout for the primary endpoint.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 21, 2024
First Posted
June 21, 2024
Study Start
August 12, 2024
Primary Completion (Estimated)
June 12, 2028
Study Completion (Estimated)
May 16, 2029
Last Updated
April 16, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- 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.
- Access Criteria
- 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.
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.