Drug Combination for Biliary Tract Cancer

Recruiting at 3 trial locations

Overseen By Gabrielle Tiggs

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nataliya Uboha

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Autoimmune disease, Transplantation, CNS metastasis, 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: 1

Duration: 6 months

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced biliary tract cancer (BTC) who have not yet received treatment for their advanced condition. Researchers are testing the safety and effectiveness of using gemcitabine, cisplatin, zimberelimab, and quemliclustat together. The trial seeks participants diagnosed with advanced BTC who have not had prior systemic treatment, although those who have tried other therapies may qualify if any recurrence occurred at least six months after completing those treatments. Participants will receive this drug combination to determine if it can help manage their cancer and improve their quality of life. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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, if you are on treatments for active autoimmune diseases or have had recent major surgery, you may need to discuss this with the trial team.

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

Research has shown that the treatments in this trial have varying safety levels based on past studies.

Gemcitabine and cisplatin, often used together to treat cancer, have a well-established safety record. Studies found that patients receiving both drugs lived longer than those receiving only gemcitabine. However, these drugs can cause side effects like low blood cell counts, potentially leading to infections or bleeding.

Quemliclustat has undergone human testing and is generally well-tolerated. Early data suggest it works well with chemotherapy and is safe for intravenous use.

Zimberelimab has also been used in studies. While effective, it can cause low white blood cell counts, increasing the risk of infections.

Overall, while past trials have tolerated these treatments, they carry some risks, particularly concerning blood cell counts. The safety run-in for this trial will help identify any early safety issues when using these drugs together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for biliary tract cancer because it introduces Quemliclustat and Zimberelimab, which are not part of the standard regimen. Quemliclustat is noteworthy as it targets CD73, an enzyme involved in cancer cell growth, potentially boosting the immune response against tumors. Zimberelimab is a novel PD-1 inhibitor that may enhance immune system activity to attack cancer cells more effectively. By combining these innovative agents with the established chemotherapy drugs Cisplatin and Gemcitabine, there’s hope for improved outcomes compared to current treatment options.

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

Research has shown that using gemcitabine and cisplatin together is a well-known treatment for advanced biliary tract cancer (BTC). One study found that 59.3% of patients did not experience cancer progression for at least six months with this combination, compared to 42.5% with gemcitabine alone. In this trial, participants will receive a combination that includes gemcitabine and cisplatin along with Zimberelimab and Quemliclustat. Zimberelimab, when used with chemotherapy, has shown promise in treating upper gastrointestinal cancers, though it can cause side effects like low white blood cell counts. Quemliclustat is a newer drug that targets a specific protein and has been well-tolerated in early studies. Initial results from a study with similar drug combinations showed an average survival time of 15.7 months, which is encouraging for pancreatic cancer, a cancer similar to BTC. These findings suggest that the combination used in this trial could be effective for untreated advanced BTC. ^{6 7 8 9 10}

Who Is on the Research Team?

Nataliya V. Uboha

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

Adults with advanced biliary tract cancers who haven't had systemic treatment for it can join. They must have measurable disease, good organ function, and no recent major surgeries or untreated brain metastasis. Participants need to be able to follow the study plan and use effective birth control if they can have children.

Inclusion Criteria

I haven't had systemic treatment for my advanced disease, but I may have had adjuvant therapy if my disease came back 6 months or more after finishing all treatments.

I understand and can follow the study's procedures.

I have been mostly active and able to care for myself in the last 28 days.

Exclusion Criteria

Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study

I have been treated with gemcitabine, cisplatin, or immune checkpoint inhibitors for bile duct cancer.

I have not had major surgery or serious injury in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Initial safety assessment involving 6 participants to screen for early safety signals of the drug combination

6 months

Multiple visits as per cycle schedule

Treatment

Participants receive 4 cycles of combination therapy with gemcitabine, cisplatin, zimberelimab, and quemliclustat. After 4 cycles, cisplatin is discontinued, and other drugs are continued until disease progression or intolerable toxicities

6 months

Day 1, 8, 22, and 29 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Gemcitabine
• Quemliclustat
• Zimberelimab

Trial Overview The trial is testing a combination of gemcitabine, cisplatin, zimberelimab (AB122), and quemliclustat (AB680) in patients with advanced biliary tract cancers. It starts with a safety check on the first 6 people before continuing up to 39 participants who will receive these drugs until their disease worsens or side effects become too much.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 4 Interventions

Quemliclustat (AB680), zimberelimab (AB122), gemcitabine, and cisplatin in subjects with untreated advanced BTC. Quemliclustat IV: Day 1, 15, and 29 of each cycle; Zimberelimab IV: Day 1 and 22 of each cycle; Gemcitabine IV: Day 1, 8, 22 and 29 of each cycle; Cisplatin IV: Day 1, 8, 22 and 29 of Cycles 1-4 only.

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?

Nataliya Uboha

Lead Sponsor

Trials

2

Recruited

40+

Arcus Biosciences, Inc.

Industry Sponsor

Trials

44

Recruited

7,500+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

Published Research Related to This Trial

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 trial involving 50 patients with inoperable biliary tract cancers, the combination of fixed-dose-rate gemcitabine and cisplatin resulted in a 26% partial response rate and a median response duration of 8.3 months.

The treatment was generally well tolerated, with low rates of severe side effects, although 38% of patients discontinued due to toxicity or personal preference, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed-dose-rate gemcitabine combined with cisplatin in patients with inoperable biliary tract carcinomas. Goldstein, D., Gainford, MC., Brown, C., 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 18 patients with unresectable biliary tract cancer, gemcitabine and cisplatin combined with radiotherapy showed a 27.8% overall response rate and a 100% disease stabilization rate, indicating its efficacy in managing this condition.

The treatment was well-tolerated, with no grade 4 adverse events or treatment-related deaths reported, although some patients experienced grade 3 side effects like thrombocytopenia and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of concurrent chemoradiotherapy with gemcitabine and cisplatin in patients with locally advanced biliary tract cancer. Lee, KJ., Yi, SW., Cha, J., et al.[2022]

In a Phase 2 trial involving 51 patients with advanced biliary tract cancer, adding the MEK inhibitor selumetinib to standard chemotherapy (Cisplatin and gemcitabine) did not improve tumor size reduction or survival outcomes compared to chemotherapy alone.

Patients receiving selumetinib experienced higher rates of severe toxicities and required more dose reductions of chemotherapy, indicating that the combination may not be safe or effective for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised, Phase II study of selumetinib, an oral inhibitor of MEK, in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer. Doherty, MK., Tam, VC., McNamara, MG., et al.[2023]

A meta-analysis of 5 studies involving 727 patients found that fluoropyrimidine-cisplatin (FP) is as effective as gemcitabine-cisplatin (GP) for treating advanced biliary tract cancer, with no significant differences in overall response rate, disease control rate, or overall survival.

FP demonstrated a significantly lower incidence of severe adverse events (grade 3/4) compared to GP, indicating a more favorable safety profile for FP in first-line chemotherapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between Fluoropyrimidine-Cisplatin and Gemcitabine-Cisplatin as First-Line Chemotherapy for Advanced Biliary Tract Cancer: A Meta-Analysis. Zheng, T., Jin, J., Zhou, L., et al.[2022]

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 of 10 patients with unresectable biliary tract cancer, the combination of cisplatin and gemcitabine was found to be a standard treatment, but it resulted in significant hematological toxicities, including grade 3/4 neutropenia in 5 patients and thrombocytopenia in 4 patients.

Despite the observed toxicities, the chemotherapy can be administered safely with close monitoring, as dose adjustments were necessary for 8 patients due to adverse effects, particularly hematological issues and anorexia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial safety and efficacy of cisplatin and gemcitabine combination chemotherapy for unresectable biliary tract cancer. Shibata, Y.[2022]

In a study of 43 patients with unresectable biliary tract cancer, the combination of gemcitabine and cisplatin showed an overall response rate of 27.5%, indicating it has potential efficacy in treating this difficult-to-treat cancer.

The treatment was generally well-tolerated, with manageable side effects, including low rates of severe hematologic toxicity, suggesting that gemcitabine plus cisplatin could be a safe option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. Thongprasert, S., Napapan, S., Charoentum, C., et al.[2022]

In a phase 3 trial involving 1069 patients with advanced biliary tract cancer, the addition of pembrolizumab to the standard chemotherapy regimen of gemcitabine and cisplatin significantly improved median overall survival from 10.9 months to 12.7 months.

The combination treatment did not introduce new safety concerns, with similar rates of severe adverse events between the pembrolizumab and placebo groups, suggesting it could be a viable new option for patients with this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Kelley, RK., Ueno, M., Yoo, C., et al.[2023]

In the phase 3 TOPAZ-1 trial, the combination of durvalumab with gemcitabine and cisplatin significantly improved overall survival and progression-free survival in adults with advanced biliary tract cancer, compared to the placebo group.

Durvalumab's benefits were consistent across various patient factors, including tumor location and PD-L1 expression levels, and the treatment was found to be manageable in terms of tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Advanced Biliary Tract Cancer. Fung, S., Syed, YY.[2023]

The combination of panitumumab with gemcitabine and irinotecan showed promising efficacy in treating advanced cholangiocarcinoma, achieving a 5-month progression-free survival (PFS) rate of 69% and a median PFS of 9.7 months among 35 patients.

The treatment was generally well-tolerated, with a disease-control rate of 74% and manageable side effects, indicating that this regimen could be a viable option for patients with unresectable or metastatic biliary tract cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma. Sohal, DP., Mykulowycz, K., Uehara, T., et al.[2022]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa0908721

Cisplatin plus Gemcitabine versus Gemcitabine for Biliary ... The 6-month progression-free survival rate was 59.3% in the cisplatin–gemcitabine group and 42.5% in the gemcitabine-only group. Figure 2.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9474496/

Real-World Outcomes of Gemcitabine, Cisplatin, and Nab ... Gemcitabine, cisplatin, and nab-paclitaxel did not improve the PFS or OS compared to that achieved by standard chemotherapy in patients with advanced BTC.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2589555924002945

A systematic review and meta-analysis using reconstructed ... Median survival with GemCis remained at 12 months over time, indicating no significant second-line treatment improvement. Background & Aims. Gemcitabine/ ...

4. academic.oup.com academic.oup.com/oncolo/article/30/8/oyae306/7905746

Real-world effectiveness and prognostic factors of durvalumab ... The TOPAZ-1 trial of durvalumab plus first-line chemotherapy (gemcitabine plus cisplatin) showed improved survival vs chemotherapy alone.

5. nature.com nature.com/articles/s41467-025-60119-3

Sintilimab and anlotinib with gemcitabine plus cisplatin in ... Patients with ICC have a better OS than those with biliary tract cancers of different primary origins. Consistently, patients with ICC in the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10453877/

Safety and Effectiveness of Chemotherapy in Elderly Biliary ... The safety and effectiveness of chemotherapy in elderly patients with biliary tract cancer (BTC) remain unclear. Therefore, we retrospectively reviewed patients ...

7. thelancet.com thelancet.com/journals/lanwpc/article/PIIS2666-6065(24)00347-X/fulltext

Updated efficacy and safety data from a phase II, single ... This study aims to provide an updated analysis of the safety and efficacy of neoadjuvant DurGAP for resectable BTC in our latest cohort of 30 patients.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11994646/

Efficacy and safety of immune checkpoint inhibitors in ... ... cisplatin chemotherapy have become the standard first-line treatment for advanced biliary tract cancer (BTC) ... data. Liver International ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/018057s080lbl.pdf

Platinol (cisplatin) label - accessdata.fda.gov PLATINOL is indicated as a single agent for patients with transitional cell bladder cancer which is no longer amenable to local treatments, such as surgery and/ ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.4093

Three-year follow-up data from KEYNOTE-966 We present updated efficacy and safety data after 11 mo of additional follow-up. ... cisplatin (gem/cis) for advanced biliary tract cancer (BTC).