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Comparing T-DXd with Rilvegostomig to Standard Treatment for Advanced HER2-expressing Biliary Tract Cancer

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

PHASE3 · AstraZeneca · NCT06467357

This study is testing if a new combination treatment for advanced biliary tract cancer can work better than the usual options for adults with this condition.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment620 (estimated)
Ages18 Years to 99 Years
SexAll
SponsorAstraZeneca (industry)
Drugs / interventionsdurvalumab
Locations266 sites (Scottsdale, Arizona and 265 other locations)
Trial IDNCT06467357 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of T-DXd combined with rilvegostomig or T-DXd alone against standard treatment options, including gemcitabine plus cisplatin and durvalumab, in patients with advanced HER2-expressing biliary tract cancer. Participants must be adults with unresectable, previously untreated, locally advanced or metastatic disease and confirmed HER2 expression. The study aims to determine which treatment regimen provides better outcomes for these patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with unresectable, previously untreated HER2-expressing biliary tract cancer.

Not a fit: Patients who have previously received HER2-targeting therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a more effective treatment option for patients with advanced HER2-expressing biliary tract cancer.

How similar studies have performed: Other studies have shown promise in targeting HER2 in biliary tract cancer, suggesting potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

* 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.

Key Exclusion Criteria:

* 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).
* Any concurrent anticancer treatment without an adequate washout period prior to randomization. Concurrent use of hormonal therapy for non-cancer related conditions (eg, hormone replacement therapy) is allowed.
* History of organ transplants or allogenic stem cell transplant.

Where this trial is running

Scottsdale, Arizona and 265 other locations

+216 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Biliary Tract Cancer, HER2, HER2 expressing BTC, Trastuzumab deruxtecan, T-DXd, Rilvegostomig

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.