Zanidatamab + Standard Therapy for Biliary Tract Cancer

Recruiting at 152 trial locations

Overseen By Clinical Trial Disclosure & Transparency

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Jazz Pharmaceuticals

Must not be taking: Corticosteroids, others

Disqualifiers: Brain metastases, Autoimmune conditions, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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 programmed death protein 1/ligand-1 (PD-1/L1) inhibitor (physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations) as first line of treatment for participants with human epidermal growth factor receptor 2 (HER2)-positive biliary tract cancer.

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.

What data supports the effectiveness of the drug Zanidatamab + Standard Therapy for Biliary Tract Cancer?

The combination of gemcitabine and cisplatin is the current standard treatment for advanced biliary tract cancer, showing median survival times of 8.0 months progression-free and 11.7 months overall. New treatments are needed to improve these outcomes, suggesting potential for Zanidatamab to enhance effectiveness. ^{1 2 3 4 5}

Is the combination of gemcitabine and cisplatin safe for treating biliary tract cancer?

The combination of gemcitabine and cisplatin has been studied for safety in treating advanced biliary tract cancer, and it is considered a standard treatment option. These studies have evaluated its safety and determined recommended doses, indicating it is generally safe for use in humans. ^{1 6 7 8 9}

What makes the drug Zanidatamab + Standard Therapy unique for biliary tract cancer?

Zanidatamab combined with standard therapy is unique because it adds a targeted therapy (Zanidatamab) to the existing standard chemotherapy regimen of gemcitabine and cisplatin, potentially offering a new approach to improve outcomes for patients with biliary tract cancer. ^{3 4 5 10 11}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Cisplatin (Chemotherapy)
• Durvalumab (Checkpoint Inhibitor)
• Gemcitabine (Chemotherapy)
• Pembrolizumab (Checkpoint Inhibitor)
• Zanidatamab (Monoclonal Antibodies)

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.

Participant Groups

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 Canada, Japan for the following indications:

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

Findings from Research

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 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]

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]

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]

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 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 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]

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 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]

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[GEM plus CDDP Combination Therapy for Unresectable Biliary Tract Cancer-A Single Institution Experience]. [2023]

2. England 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. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. Korea (South) 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. [2022]

5. 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]

6. Korea (South) 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. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

Phase I study of gemcitabine, cisplatin, and S-1 combination therapy for patients with untreated advanced biliary tract cancer. [2022]

8. England 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. [2022]

9. China (Republic : 1949- ) 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. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial. [2022]

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

A phase II trial of S-1 and cisplatin in patients with metastatic or relapsed biliary tract cancer. [2020]