Zanidatamab for Biliary Tract Cancer

(HERIZON-BTC-01 Trial)

No longer recruiting at 85 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called zanidatamab to determine its effectiveness against certain types of advanced biliary tract cancer, which affects the bile ducts and gallbladder. Researchers aim to discover if zanidatamab can shrink tumors in patients whose cancer has spread and cannot be surgically removed. The trial seeks participants with HER2-positive biliary tract cancer who have previously undergone chemotherapy and experienced cancer progression. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from a promising new therapy.

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.

Is there any evidence suggesting that ZW25 (zanidatamab) is likely to be safe for humans?

Research has shown that zanidatamab is generally well-tolerated by patients with HER2-positive biliary tract cancer (BTC). In one study, zanidatamab showed promising results in shrinking tumors. Patients experienced a median progression-free survival of 6.7 months, meaning their cancer did not worsen during that time. The overall response rate, indicating how well tumors respond to treatment, was 65%.

Another study examined zanidatamab combined with chemotherapy drugs (cisplatin and gemcitabine) for HER2-expressing BTC. This research also highlighted the treatment's effectiveness and safety. While specific side effects were not detailed, the consistent use of zanidatamab in various studies suggests that any side effects are usually manageable, meaning they are generally not severe enough to stop the treatment.

Overall, zanidatamab appears to be a promising option for BTC, with controlled safety findings so far. However, discussing potential risks and benefits with a healthcare provider before joining a clinical trial is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for biliary tract cancer?

Unlike the standard treatments for biliary tract cancer, which primarily include chemotherapy and targeted therapies, Zanidatamab is a novel bispecific antibody. It uniquely targets two different sites on the HER2 protein, which is often overexpressed in this type of cancer. This dual targeting approach could potentially enhance its ability to inhibit tumor growth and improve patient outcomes. Researchers are excited about Zanidatamab because it represents a new mechanism of action that might offer improved effectiveness compared to existing therapies.

What evidence suggests that zanidatamab might be an effective treatment for biliary tract cancer?

Studies have shown that zanidatamab is promising for treating biliary tract cancer (BTC) in patients with HER2-positive tumors, where the cancer has a protein that can affect its growth. In real-world patients, zanidatamab prevented cancer progression for an average of 6.7 months and caused the cancer to shrink or disappear in 65% of patients. Additionally, with nearly two years of follow-up, patients lived for an average of 15.5 months after starting treatment. These findings suggest that zanidatamab can be an effective treatment option for people with advanced biliary tract cancer. ^{2 6 7 8 9}

Who Is on the 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.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Jazz Pharmaceuticals Ireland Limited

Industry Sponsor

Trials

2

Recruited

250+

BeiGene

Industry Sponsor

Trials

216

Recruited

32,500+

BeOne Medicines LTD

Collaborator

BeiGene, Ltd.

Collaborator

Trials

3

Recruited

1,000+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925002138

Real-world efficacy of zanidatamab in patients with HER2 ... Zanidatamab demonstrated benefit in HER2-positive BTC in real-world patients. Zanidatamab showed a median PFS of 6.7 months and ORR of 65%.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40319675/

Real-world efficacy of zanidatamab in patients with HER2 ... After a median follow-up of 8.5 (95 % confidence interval [CI]: 3.3-11.8) months, the median PFS was 6.7 (95 % CI 1.3-11.8) months, with an ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.4091

Zanidatamab in previously-treated HER2-positive (HER2+) ... Conclusions: With close to 2 years of median follow-up, zanidatamab demonstrated a median OS of 15.5 months and a median duration of response of ...

4. ccanewsonline.com ccanewsonline.com/special-issues/2021-year-in-review-cca/zanidatamab-zw25-in-her2-positive-biliary-tract-cancers-results-from-a-phase-1-study

Zanidatamab (ZW25) in HER2-Positive Biliary Tract Cancers Updated data from the TOPAZ-1 study revealed improved median overall survival for the full patient population and no new safety signals. ... Final analysis of the ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06282575

NCT06282575 | Efficacy and Safety of Zanidatamab With ... The purpose of this study is to evaluate the efficacy and safety of Zanidatamab plus CisGem (Cisplatin and Gemcitabine) with or without the addition of a ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06282575

NCT06282575 | Efficacy and Safety of Zanidatamab With ... The purpose of this study is to evaluate the efficacy and safety of Zanidatamab plus CisGem (Cisplatin and Gemcitabine) with or without the addition of a ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00537-X/fulltext

319P Antitumour activity and safety of first-line ... Here, we report antitumour activity and safety of first-line (1L) zani + cisplatin-gemcitabine (CisGem) in pts with HER2-expressing BTC. Methods. In this phase ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03929666

NCT03929666 | A Safety and Efficacy Study of ZW25 ... This is a multicenter, global, Phase 2, open-label, 2-part, first-line study to investigate the safety, tolerability, and anti-tumor activity of ZW25 ...

9. ir.zymeworks.com ir.zymeworks.com/static-files/66959f47-a3f6-4c7b-9540-80d90b84187e

Zanidatamab (ZW25) in HER2-positive Biliary Tract Cancer ... Data extracted on: Nov 16, 2020 (data are from an unlocked database and subject to change). Efficacy. • Twenty (95%) patients were response-evaluable. Figure 2: ...