Recruiting
Phase 3

T-DXd & Rilvegostomig

Sponsor:

AstraZeneca

Code:

NCT06467357

Conditions

Biliary Tract Cancer

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Gemcitabine

Cisplatin

Durvalumab

Trastuzumab deruxtecan

Rilvegostomig

Study Details

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.

Conditions

Biliary Tract Cancer

Study ID

NCT06467357

Start date

Aug 12, 2024

Status verified date

Aug, 2026

Completion date

May 16, 2029

Anticipated

Primary completion date

Jun 12, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

620 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

Interventions

Gemcitabine

Standard of care chemotherapy by intravenous infusion

Cisplatin

Standard of care chemotherapy by intravenous infusion

Durvalumab

Standard of care immunotherapy by intravenous infusion

Trastuzumab deruxtecan

Experimental therapy by intravenous infusion

Rilvegostomig

Experimental therapy by intravenous infusion

Primary outcome measure

  • Safety Run In: To evaluate the safety and tolerability of T-DXd with rilvegostomig [ Time Frame: 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 [ Time Frame: 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) ]

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

1-877-240-9479information.center@astrazeneca.com

Locations

Research Site

Recruiting

Scottsdale, Arizona, United States, 85259

Research Site

Recruiting

Tucson, Arizona, United States, 85719

Research Site

Recruiting

Fullerton, California, United States, 92835

Research Site

Recruiting

La Jolla, California, United States, 92093

Research Site

Recruiting

Los Angeles, California, United States, 90017

Research Site

Recruiting

Los Angeles, California, United States, 90089

Research Site

Recruiting

San Francisco, California, United States, 94143

Research Site

Recruiting

Fort Myers, Florida, United States, 33901

Research Site

Recruiting

Jacksonville, Florida, United States, 32224

Research Site

Recruiting

St. Petersburg, Florida, United States, 33705

Research Site

Recruiting

West Palm Beach, Florida, United States, 33401

Research Site

Recruiting

Atlanta, Georgia, United States, 30309

Research Site

Recruiting

Chicago, Illinois, United States, 60612

Research Site

Recruiting

Niles, Illinois, United States, 60714

Research Site

Recruiting

Towson, Maryland, United States, 21204

Research Site

Recruiting

Grand Rapids, Michigan, United States, 49503

Research Site

Recruiting

Rochester, Minnesota, United States, 55905

Research Site

Recruiting

Kansas City, Missouri, United States, 64132

Research Site

Recruiting

St Louis, Missouri, United States, 63110

Research Site

Recruiting

White Plains, New York, United States, 10601

Research Site

Recruiting

Cleveland, Ohio, United States, 44195

Research Site

Recruiting

Columbus, Ohio, United States, 43210

Research Site

Recruiting

Greenville, South Carolina, United States, 29605

Research Site

Recruiting

Dallas, Texas, United States, 75246

Research Site

Recruiting

Fort Worth, Texas, United States, 76104

Research Site

Recruiting

Houston, Texas, United States, 77030

Research Site

Recruiting

Fairfax, Virginia, United States, 22031

Research Site

Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Research Site

Recruiting

Halifax, Nova Scotia, Canada, B3H 1V7

Research Site

Recruiting

Brampton, Ontario, Canada, L6R 3J7

Research Site

Recruiting

Toronto, Ontario, Canada, M5G 2M9

Research Site

Recruiting

Montreal, Quebec, Canada, H3A 1A1

More Information

Sponsor

AstraZeneca

Last update posted

Aug 19, 2026

Last verified

Aug, 2026

Keywords

  • Biliary Tract Cancer
  • HER2
  • HER2 expressing BTC
  • Trastuzumab deruxtecan
  • T-DXd
  • Rilvegostomig

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by AstraZeneca on 2026-08-19.