Zanidatamab for Biliary Tract Cancer

(HERIZON-BTC-01 Trial)

Recruiting at 73 trial locations

Overseen By Zymeworks Clinical Trial Resource

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jazz Pharmaceuticals

Must not be taking: HER2-targeted agents

Disqualifiers: CNS metastases, Active hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 34 months

87 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a drug called zanidatamab on patients with advanced biliary tract cancer that cannot be operated on. The drug targets a specific protein on cancer cells to help stop their growth and spread.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received any systemic anti-cancer therapy within 3 weeks of starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Zanidatamab for treating biliary tract cancer?

Zanidatamab has shown promising results in early trials for biliary tract cancer that overexpresses HER2, a protein that can promote cancer growth. It has demonstrated tolerability and initial anti-tumor activity in patients whose cancer did not respond to other treatments. ^{1 2 3 4 5}

Is Zanidatamab (ZW25) safe for humans?

Early phase trials of zanidatamab, a bispecific HER2-antibody, have shown encouraging response rates, suggesting it may be safe for use in humans, although specific safety data for biliary tract cancer is not detailed in the available research. ^{2 6 7 8 9}

How is the drug Zanidatamab different from other treatments for biliary tract cancer?

Zanidatamab is unique because it is a bispecific antibody that targets two different parts of the HER2 protein, which is overexpressed in some biliary tract cancers. This approach is different from standard chemotherapy and offers a targeted treatment option for patients with HER2-amplified biliary tract cancer. ^{1 2 3 10 11}

Research Team

Bhardwaj Desai, MD

Principal Investigator

Zymeworks Inc.

Phil Garfin, MD, PhD

Principal Investigator

Zymeworks Inc.

Jiafang Ma, MD

Principal Investigator

BeiGene, Ltd.

Phillip Garfin, MD, PhD

Principal Investigator

Zymeworks Inc.

Eligibility Criteria

Adults with advanced or metastatic HER2-amplified biliary tract cancers, who've had prior gemcitabine chemotherapy but saw their disease progress or couldn't tolerate it. They must have good organ and heart function (ejection fraction ≥ 50%), no recent cancer treatments, no history of HER2-targeted therapy, controlled brain metastases if present, and no significant concurrent illnesses.

Inclusion Criteria

My cancer is a type of bile duct cancer confirmed by lab tests.

My cancer is HER2 positive based on a specific lab test, not from a fine needle aspirate or bone biopsy.

My organs are working well.

Exclusion Criteria

I don't have any other cancers that could affect this treatment's safety or results.

I haven't had cancer treatment or radiotherapy in the last 3 weeks.

I have stable, treated brain metastases and am not on steroids or anticonvulsants.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ZW25 (zanidatamab) monotherapy to evaluate anti-tumor activity

Up to 34 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ZW25 (Zanidatamab)

Trial Overview The trial is testing ZW25 (zanidatamab), a new medication targeting the HER2 protein in patients with specific types of biliary tract cancer that cannot be surgically removed. It's an open-label study where all participants receive the drug to see how well it works against their cancer.

Participant Groups

Group I: ZW25 (Zanidatamab) Monotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Jazz Pharmaceuticals

Lead Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Zymeworks Inc.

Lead Sponsor

Trials

11

Recruited

2,400+

BeiGene

Industry Sponsor

Trials

216

Recruited

32,500+

BeiGene, Ltd.

Collaborator

Trials

3

Recruited

1,000+

Findings from Research

Biliary tract cancers, including cholangiocarcinomas and gallbladder cancers, are on the rise and typically have a poor prognosis, with palliative chemotherapy being the main treatment for advanced cases.

Targeted therapies, such as pemigatinib for FGFR2 gene fusions and ivosidenib for IDH1 mutations, have shown promising results in improving patient outcomes, leading to FDA approvals and encouraging response rates in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and emerging therapies for advanced biliary tract cancers. Kam, AE., Masood, A., Shroff, RT.[2022]

The addition of nab-paclitaxel to the standard gemcitabine-cisplatin therapy for advanced biliary tract cancers resulted in a median progression-free survival of 11.8 months and a median overall survival of 19.2 months, which are improvements over historical controls that only received gemcitabine-cisplatin.

Despite a high incidence of grade 3 or higher adverse events (58%), including neutropenia in 33% of patients, the treatment was generally well-tolerated, especially at reduced doses, indicating a potential for better management of side effects while improving survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. Shroff, RT., Javle, MM., Xiao, L., et al.[2022]

Gemcitabine plus platinum chemotherapy is the standard first-line treatment for advanced biliary tract cancers (BTC), while the FOLFOX regimen is the only validated second-line therapy, showing only modest survival benefits over best supportive care.

Recent advancements in genomic analyses have revealed the molecular diversity of BTC, paving the way for personalized targeted therapies, particularly focusing on fibroblast growth factor receptor and isocitrate dehydrogenase gene alterations, as well as combination immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuum of care for advanced biliary tract cancers. Vienot, A., Neuzillet, C.[2021]

Nivolumab, either alone or combined with chemotherapy, demonstrated a manageable safety profile in Japanese patients with unresectable or recurrent biliary tract cancer, with the most common side effects being decreased appetite and neutrophil count decrease.

The combination therapy cohort showed significantly better outcomes, with a median overall survival of 15.4 months and an objective response rate of 37%, compared to the monotherapy cohort's median overall survival of 5.2 months and a 3% response rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab alone or in combination with cisplatin plus gemcitabine in Japanese patients with unresectable or recurrent biliary tract cancer: a non-randomised, multicentre, open-label, phase 1 study. Ueno, M., Ikeda, M., Morizane, C., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Current and emerging therapies for advanced biliary tract cancers. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. [2022]

4. China pubmed.ncbi.nlm.nih.gov

Cholangiocarcinoma: the quest for a second-line systemic treatment. [2022]

5. France pubmed.ncbi.nlm.nih.gov

Continuum of care for advanced biliary tract cancers. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Tumor Mutational Burden Is a Potential Predictive Biomarker for Response to Immune Checkpoint Inhibitors in Patients With Advanced Biliary Tract Cancer. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Nivolumab alone or in combination with cisplatin plus gemcitabine in Japanese patients with unresectable or recurrent biliary tract cancer: a non-randomised, multicentre, open-label, phase 1 study. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Feasibility and tolerability of sintilimab plus anlotinib as the second-line therapy for patients with advanced biliary tract cancers: An open-label, single-arm, phase II clinical trial. [2023]

9. Greece pubmed.ncbi.nlm.nih.gov

A pilot study of salvage irinotecan monotherapy for advanced biliary tract cancer. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

A phase II trial of the proteasome inhibitor bortezomib in patients with advanced biliary tract cancers. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial. [2022]