Phase 3 Study of T-DXd and Rilvegostomig Versus SoC in Advanced HER2-expressing Biliary Tract Cancer

Purpose

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.

Condition

  • Biliary Tract Cancer

Eligibility

Eligible Ages
Between 18 Years and 99 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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.

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

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Masking Description
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.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Trastuzumab deruxtecan + rilvegostomig 		Trastuzumab deruxtecan (T-DXd; DS-8201a) in combination with rilvegostomig arm
  • Drug: Trastuzumab deruxtecan
    Experimental therapy by intravenous infusion
    Other names:
    • DS-8201a; T-DXd
  • Drug: Rilvegostomig
    Experimental therapy by intravenous infusion
Experimental
Trastuzumab deruxtecan 		Trastuzumab deruxtecan (T-DXd; DS-8201a) arm
  • Drug: Trastuzumab deruxtecan
    Experimental therapy by intravenous infusion
    Other names:
    • DS-8201a; T-DXd
  • Drug: Rilvegostomig
    Experimental therapy by intravenous infusion
Active Comparator
Standard of Care 		Gemcitabine and cisplatin in combination with durvalumab arm
  • Drug: Gemcitabine
    Standard of care chemotherapy by intravenous infusion
  • Drug: Cisplatin
    Standard of care chemotherapy by intravenous infusion
  • Drug: Durvalumab
    Standard of care immunotherapy by intravenous infusion

Recruiting Locations

Research Site
Scottsdale, Arizona 85259

Research Site
Tucson, Arizona 85719

Research Site
Fullerton, California 92835

Research Site
La Jolla, California 92093

Research Site
Los Angeles, California 90017

Research Site
Los Angeles, California 90089

Research Site
San Francisco, California 94143

Research Site
Fort Myers, Florida 33901

Research Site
Jacksonville, Florida 32224

Research Site
St. Petersburg, Florida 33705

Research Site
West Palm Beach, Florida 33401

Research Site
Atlanta, Georgia 30309

Research Site
Chicago, Illinois 60612

Research Site
Niles, Illinois 60714

Research Site
Towson, Maryland 21204

Research Site
Grand Rapids, Michigan 49503

Research Site
Rochester, Minnesota 55905

Research Site
Kansas City, Missouri 64132

Research Site
St Louis, Missouri 63110

Research Site
White Plains, New York 10601

Research Site
Cleveland, Ohio 44195

Research Site
Columbus, Ohio 43210

Research Site
Greenville, South Carolina 29605

Research Site
Dallas, Texas 75246

Research Site
Fort Worth, Texas 76104

Research Site
Houston, Texas 77030

Research Site
Fairfax, Virginia 22031

More Details

Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com