Zanidatamab + Standard Therapy for Biliary Tract Cancer

Recruiting at 239 trial locations

Overseen By Clinical Trial Disclosure & Transparency

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Jazz Pharmaceuticals

Must not be taking: Corticosteroids, others

Disqualifiers: Brain metastases, Autoimmune conditions, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 52 months

286 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with HER2-positive biliary tract cancer, which affects the bile ducts and gallbladder. Researchers aim to evaluate the effectiveness of Zanidatamab, an experimental treatment, when combined with standard chemotherapy drugs, Cisplatin and Gemcitabine, with or without additional drugs that enhance the immune system's ability to fight cancer. It targets those with advanced cancer that cannot be surgically removed and who have not received more than two cycles of standard treatment. For those with HER2-positive biliary tract cancer, this trial might be suitable. As a Phase 3 trial, it represents the final step before FDA approval, offering access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does exclude participants using systemic corticosteroids and those with certain medical conditions, so it's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Zanidatamab is generally well tolerated by patients with HER2-positive biliary tract cancer. One study found it helped control the cancer and was mostly safe for participants. Most experienced manageable side effects, with no severe side effects reported.

Cisplatin and Gemcitabine, often referred to as CisGem, are common chemotherapy drugs. Patients usually tolerate them, though some may experience typical side effects like nausea or tiredness.

For the PD-1/L1 inhibitors Durvalumab and Pembrolizumab, research indicates they are generally safe and well tolerated. The FDA has already approved these treatments for other types of cancer, suggesting a good safety record.

Overall, previous research has shown that the treatments tested in this study are safe, with most side effects being mild and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Zanidatamab for biliary tract cancer because it targets HER2, a protein that can promote the growth of cancer cells. Unlike standard treatments like Cisplatin and Gemcitabine, which are chemotherapy drugs that attack rapidly dividing cells, Zanidatamab is a monoclonal antibody that specifically binds to HER2, potentially leading to more targeted cancer cell destruction with fewer side effects. Additionally, this treatment can be used in combination with PD-1/L1 inhibitors, which help the immune system recognize and attack cancer cells, offering a dual approach to combat the disease. This novel mechanism and combination strategy provide hope for improved outcomes in a condition that traditionally has limited treatment options.

What evidence suggests that this trial's treatments could be effective for biliary tract cancer?

Research has shown that Zanidatamab may help treat HER2-positive biliary tract cancer. In studies, patients taking Zanidatamab lived for about 6.7 months without their cancer worsening, and 65% experienced tumor shrinkage or halted progression. Some research also found that patients lived for a median of 15.5 months overall, suggesting it might help extend life. This trial will evaluate one arm of Zanidatamab in combination with standard treatments like Cisplatin and Gemcitabine, with or without a PD-1/L1 inhibitor. These findings suggest that Zanidatamab, especially when combined with these standard treatments, could be a promising option for this type of cancer. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced HER2-positive biliary tract cancer. Participants should be starting their first treatment and can handle chemotherapy. They must not have had previous treatments that target the PD-1/L1 pathways or therapies specifically for HER2.

Inclusion Criteria

My cancer is HER2-positive based on specific lab tests.

My cancer's growth can be tracked using specific criteria.

My bile duct cancer cannot be removed by surgery and is not eligible for curative treatments.

Exclusion Criteria

Active or prior autoimmune inflammatory conditions

Participation in another clinical trial with an investigational medicinal product within the last 3 months

I have a severe ongoing infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Zanidatamab plus CisGem with or without a PD-1/L1 inhibitor as first line of treatment for HER2-positive biliary tract cancer

Up to 52 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 68 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Durvalumab
• Gemcitabine
• Pembrolizumab
• Zanidatamab

Trial Overview The study tests Zanidatamab combined with Cisplatin and Gemcitabine (CisGem), with an optional addition of a PD-1/L1 inhibitor (Durvalumab or Pembrolizumab). It's to see if this mix works better as a first-line treatment compared to just CisGem.

How Is the Trial Designed?

Group I: Zanidatamab with Standard-of-care Therapy Arm Experimental Treatment 5 Interventions

Zanidatamab plus standard of care treatment of CisGem with or without a PD-1/L1 inhibitor. PD-1/L1 inhibitor will be physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations.

Group II: Standard-of-care Therapy Arm Active Control 4 Interventions

Standard of care treatment of CisGem with or without a PD-1/L1 inhibitor. PD-1/L1 inhibitor will be physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

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

Published Research Related to This Trial

In a study of 51 patients with advanced biliary tract cancer, combination chemotherapy with S-1 and cisplatin resulted in a 30% overall response rate, with a median overall survival of 8.7 months.

The treatment was associated with manageable toxicity, including grade 3/4 neutropenia occurring in 8.9% of cycles, indicating that while the regimen is effective, it also requires monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of S-1 and cisplatin in patients with metastatic or relapsed biliary tract cancer. Kim, YJ., Im, SA., Kim, HG., et al.[2020]

In a phase 2 trial involving 150 patients with advanced biliary cancers, the addition of cetuximab to standard chemotherapy (gemcitabine and oxaliplatin) did not significantly improve progression-free survival compared to chemotherapy alone, with median progression-free survival of 6.1 months versus 5.5 months, respectively.

While cetuximab was well tolerated, the study found a higher incidence of grade 3-4 adverse events in the cetuximab group, suggesting that the standard chemotherapy regimen should remain the preferred treatment for advanced biliary cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial. Malka, D., Cervera, P., Foulon, S., et al.[2022]

In a study involving 117 patients with advanced biliary tract cancer, rising levels of circulating VEGFA were linked to worse progression-free survival (PFS) and overall survival (OS) in those treated with cisplatin/gemcitabine, but this negative effect was reduced in patients receiving cediranib.

The study found that increases in circulating CK18 and VEGFR2 levels were associated with poorer outcomes, suggesting these markers could help predict patient prognosis and treatment response, highlighting the potential for using minimally invasive biomarkers in managing advanced biliary tract cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial. Backen, AC., Lopes, A., Wasan, H., et al.[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]

In a phase I study involving 18 patients with untreated advanced biliary tract cancer, the triplet regimen of gemcitabine, cisplatin, and S-1 (GPS) was found to be safe, with dose-limiting toxicities occurring in only a few patients.

The treatment demonstrated preliminary antitumor activity, achieving a 50% response rate among 14 patients with measurable lesions, indicating potential efficacy for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of gemcitabine, cisplatin, and S-1 combination therapy for patients with untreated advanced biliary tract cancer. Moriwaki, T., Ishida, H., Araki, M., et al.[2022]

In a study of 29 patients with unresectable biliary tract cancer, the combination therapy of gemcitabine (GEM) and cisplatin (CDDP) demonstrated a disease control rate of 66.7%, indicating its effectiveness as a treatment option.

The therapy was found to be safe, with manageable adverse effects; the most common severe hematological toxicity was neutropenia (65.5%), but there were no cases of interstitial pneumonia reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[GEM plus CDDP Combination Therapy for Unresectable Biliary Tract Cancer-A Single Institution Experience]. Muneta, M., Ohmura, Y., Takeda, Y., et al.[2023]

In a phase II study involving 32 chemotherapy-naive patients with advanced biliary tract cancer, the novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) achieved a 50% objective response rate, indicating promising efficacy as a first-line treatment.

The median overall survival for patients treated with OIS was 12.5 months, suggesting that this combination may improve outcomes compared to the standard treatment, although further randomized studies are necessary for direct comparison.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer. Yoo, C., Han, B., Kim, HS., et al.[2022]

A comprehensive analysis of 161 trials involving 6,337 patients found that the standard gemcitabine platinum (GP) chemotherapy has a median overall survival of 9.5 months and a tumor control rate of 63.5%.

Newer treatment regimens, including triplet combinations of gemcitabine, fluoropyrimidine, and platinum (GFP) or gemcitabine with targeted therapies, showed significantly better tumor control and overall survival compared to the standard GP regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Eckel, F., Schmid, RM.[2022]

The study established that the maximum tolerated dose and recommended dose for the combination of S-1, gemcitabine, and cisplatin in treating advanced biliary tract adenocarcinoma is level 0: gemcitabine at 800 mg/m²/week, cisplatin at 25 mg/m²/week, and S-1 at 40 mg/m²/day, based on treatment of 17 patients.

The treatment regimen was well tolerated, with some dose-limiting toxicities observed, and it demonstrated promising antitumor activity, with five partial responses noted among the participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of oral administration of S-1 in combination with intravenous gemcitabine and cisplatin in patients with advanced biliary tract cancer. Shoji, H., Morizane, C., Sakamoto, Y., et al.[2022]

In a study of 34 patients with advanced biliary tract cancer, the combination of nab-paclitaxel, gemcitabine, and cisplatin resulted in a median progression-free survival of 7.1 months and overall survival of 16.4 months, indicating promising therapeutic potential.

The treatment was associated with significant adverse effects, particularly neutropenia and leukopenia in 26.5% of patients, while biomarkers like carcinoembryonic antigen (CEA) levels and immune cell changes were identified as potential indicators of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single-Arm Phase II Study of Nab-Paclitaxel Plus Gemcitabine and Cisplatin for Locally Advanced or Metastatic Biliary Tract Cancer. Liu, T., Li, Q., Lin, Z., et al.[2023]

In a study of 30 chemotherapy-naïve patients with advanced biliary tract carcinoma, the gemcitabine-cisplatin combination showed a partial response in 16.7% of patients and a median overall survival of 13.4 months, indicating its efficacy as a treatment option.

The treatment was associated with manageable toxicity, with major adverse events including infections and anemia, but importantly, there were no treatment-related deaths, highlighting the safety of this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy with gemcitabine plus cisplatin in patients with advanced biliary tract carcinoma at Chang Gung Memorial Hospital: a retrospective analysis. Wu, CE., Hsu, HC., Shen, WC., 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 ... The benefits of in patients with HER2-positive BTC were confirmed. Zanidatamab should be considered for patients with this condition.

3. 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 ...

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 Of the 17 patients who were evaluable for response, the confirmed overall response rate was 47% (n = 8), all of which were partial responses. Five additional ...

5. 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 ...

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

319P Antitumour activity and safety of first-line ... 319P Antitumour activity and safety of first-line zanidatamab + cisplatin-gemcitabine in patients with HER2-expressing biliary tract cancer (BTC) · Download PDF ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.3_suppl.299

Zanidatamab (ZW25) in HER2-positive biliary tract cancers ... Conclusions: Zanidatamab is well tolerated with promising and durable anti-tumor activity in patients with HER2 overexpressing BTC. Based on ...