An Open-label Randomized Trial of the Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy Alone for Advanced HER2-positive Biliary Tract Cancer

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Moderate burden on patient More information

Trial Details

Sponsor: Jazz Pharmaceuticals (industry)

Phase: 3

Start date: July 19, 2024

Planned enrollment: 286

Trial ID: NCT06282575
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More trial details at ClinicalTrials.gov More info

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Investigational Drug AI Analysis

No investigational drugs.

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Goal: Evaluate whether adding zanidatamab to first-line cisplatin/gemcitabine (CisGem), with or without a PD-1/L1 inhibitor (durvalumab or pembrolizumab per local practice), improves efficacy and maintains acceptable safety in HER2-positive advanced biliary tract cancer, with a primary focus on PFS in IHC 3+ tumors.

Patients: Adults with histologically or cytologically confirmed HER2-positive biliary tract cancer (gallbladder cancer, intrahepatic or extrahepatic cholangiocarcinoma), unresectable or metastatic, ECOG 0–1, and adequate organ function. Patients may have received up to two cycles of first-line CisGem with or without durvalumab or pembrolizumab. Exclusions include prior HER2-targeted therapy; prior checkpoint inhibitors other than durvalumab or pembrolizumab; active brain metastases; significant autoimmune disease, ILD/pneumonitis, severe infections; recent investigational therapy; and certain non-adenocarcinoma histologies.

Design: Multicenter, open-label, randomized phase 3 study comparing zanidatamab plus standard-of-care versus standard-of-care alone. Allocation is randomized with efficacy assessed primarily in the IHC 3+ subset and secondarily in the overall HER2-positive population. Approximately 286 participants will be enrolled.

Treatments: Experimental arm: zanidatamab combined with CisGem and optional PD-1/L1 inhibitor (durvalumab or pembrolizumab per local regulations). Control arm: CisGem with optional durvalumab or pembrolizumab per standard-of-care. Zanidatamab is a humanized bispecific/bi-epitopic anti-HER2 monoclonal antibody that binds two distinct HER2 epitopes to enhance receptor clustering, internalization, and immune-mediated cytotoxicity. It has shown antitumor activity and manageable safety in early-phase studies across HER2-expressing solid tumors, including biliary tract cancer, with responses observed particularly in IHC 3+ disease. The standard CisGem backbone is the established first-line regimen in advanced BTC; durvalumab or pembrolizumab may be added per current practice and local approvals.

Outcomes: Primary: Progression-free survival in participants with IHC 3+ tumors. Key secondary: Overall survival in IHC 3+ tumors; PFS and OS in all randomized participants; confirmed objective response rate; duration of response; safety and treatment-emergent adverse events; zanidatamab pharmacokinetics and immunogenicity (Cmax and anti-drug antibodies). Patient-reported outcomes include time to definitive deterioration in physical function (EORTC QLQ-C30) and symptom domains relevant to BTC (EORTC QLQ-BIL21: pain, jaundice, abdominal pain, pruritus) in IHC 3+ and overall populations.

Burden on patient: Moderate. Treatment requires intravenous infusions of gemcitabine and cisplatin on a 21-day schedule, with optional durvalumab or pembrolizumab infusions, plus additional zanidatamab infusions in the experimental arm, increasing chair time and visit frequency relative to chemotherapy alone. Baseline and on-treatment tumor assessments per RECIST, routine labs, and monitoring for chemotherapy- and immunotherapy-related toxicities are standard; added burdens include HER2 central testing on archival or new biopsy tissue and pharmacokinetic/immunogenicity blood draws for zanidatamab over multiple cycles. No intensive phase 1-style PK schedules are described, and imaging frequency is expected to align with standard practice, so overall burden is higher than SOC alone but typical for a phase 3 combination trial.

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No email / No phone

Status: Recruiting

Atlantic Health System/Morristown Medical Center

Morristown, New Jersey, 07960, United States

No email / No phone

Status: Recruiting

Laura and Isaac Perlmutter Cancer Center at NYU Langone - Ambulatory Care Center

New York, New York, 10016, United States

No email / No phone

Status: Recruiting

Memorial Sloan Kettering Cancer Centers

New York, New York, 10022, United States

No email / No phone

Status: Recruiting

Saint Francis Cancer Center

Greenville, South Carolina, 29607, United States

No email / No phone

Status: Recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

No email / No phone

Status: Recruiting

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

No email / No phone

Status: Recruiting

Texas Oncology - DFW

Dallas, Texas, 75246, United States

No email / No phone

Status: Recruiting

The Univerrsity of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

No email / No phone

Status: Recruiting

Virginia Commonwealth University, VCU Health

Richmond, Virginia, 23219, United States

No email / No phone

Status: Recruiting

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