Rilvegostomig + Chemotherapy for Biliary Tract Cancer

(ARTEMIDE-Bil01 Trial)

Recruiting at 187 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants

Disqualifiers: Metastatic disease, Autoimmune disorders, others

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: 6 months

750 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment for individuals who have undergone surgery to remove biliary tract cancer (BTC), which affects the tubes carrying bile in and out of the liver. Researchers aim to determine if the new drug, rilvegostomig (an experimental treatment), is more effective when combined with chemotherapy compared to chemotherapy alone. Participants will receive either rilvegostomig plus chemotherapy or a placebo (a harmless substance) plus chemotherapy. This trial is ideal for those who have had surgery to remove BTC and are currently disease-free according to recent imaging. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have used immunosuppressive medication within 14 days before the first dose.

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

Research has shown that rilvegostomig, when combined with chemotherapy, has a manageable safety profile. Most side effects are mild and controllable. Studies have found that it works well with chemotherapy, and patients usually tolerate it without major issues.

The chemotherapy options in this trial—Capecitabine, Gemcitabine/Cisplatin, and S-1—are widely used treatments. They have known side effects, but doctors manage them effectively.

Overall, based on previous research and current medical practices, the treatments in this trial are considered safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Rilvegostomig is unique because it introduces a new active ingredient that targets specific pathways in biliary tract cancer cells, potentially disrupting their growth more effectively than traditional treatments. Most treatments like Capecitabine or the combination of Gemcitabine with Cisplatin work by interfering with cancer cell DNA or replication processes, but Rilvegostomig's distinct mechanism may offer a more targeted approach. Researchers are excited about Rilvegostomig as it could enhance the effectiveness of existing chemotherapy options, offering new hope for patients with this challenging condition.

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

This trial will compare the effects of Rilvegostomig combined with chemotherapy to a placebo combined with chemotherapy for treating biliary tract cancer. Research has shown that combining Rilvegostomig with chemotherapy may be promising for this condition. Studies have found that this combination is generally safe and effectively targets the cancer. Rilvegostomig changes "cold" tumors, which the immune system struggles to attack, into "hot" tumors, which the immune system can fight more easily. These early results suggest that using Rilvegostomig with chemotherapy could be more effective than standard treatments. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals who've had surgery to remove biliary tract cancer and are now disease-free. They should have a performance status indicating they can carry out daily activities with ease or minor limitations, and must not have used immunosuppressive drugs recently, nor have autoimmune disorders, severe diseases, recent thromboembolic events, or active hepatitis infections.

Inclusion Criteria

My bile duct cancer was confirmed by a lab test and has been fully removed.

I can provide a tumor sample from my surgery.

I am fully active or can carry out light work.

Exclusion Criteria

My cancer is ampullary, neuroendocrine, mixed, or non-epithelial.

My cancer was advanced or had spread at the time of diagnosis.

I have an autoimmune or severe uncontrolled disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Rilvegostomig or placebo in combination with chemotherapy as adjuvant treatment

6 months

Follow-up

Participants are monitored for recurrence-free survival and overall survival

5-7 years

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Gemcitabine/Cisplatin
• Rilvegostomig
• S-1 [Tegafur/Oteracil/gimeracil]

Trial Overview The study compares the effectiveness of Rilvegostomig plus chemotherapy against a placebo combined with chemotherapy in patients who've undergone surgery for biliary tract cancer. The goal is to see if Rilvegostomig can prevent the cancer from coming back.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 4 Interventions

Rilvegostomig IV infusion + Investigator choice of chemotherapy (Capecitabine or Gemcitabine/Cisplatin or S-1)

Group II: Arm B Placebo Group 4 Interventions

Placebo IV infusion + Investigator choice of chemotherapy (Capecitabine or Gemcitabine/Cisplatin or S-1)

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

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]

In a study of 16 patients with advanced biliary tract carcinoma, oral tegafur-uracil combined with leucovorin was found to be well tolerated, with only two patients experiencing significant toxicities (grade III/IV).

Despite its safety profile, the treatment showed no objective responses, with the majority of patients experiencing disease progression, indicating that it is ineffective for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of tegafur-uracil plus leucovorin (LV) in the treatment of advanced biliary tract carcinomas. Chen, JS., Yang, TS., Lin, YC., et al.[2019]

In a phase III trial involving 222 patients with metastatic biliary tract cancers, XELOX (capecitabine plus oxaliplatin) demonstrated noninferiority to GEMOX (gemcitabine plus oxaliplatin) in terms of 6-month progression-free survival, with rates of 46.7% for XELOX and 44.5% for GEMOX.

XELOX was associated with fewer hospital visits compared to GEMOX, indicating a potentially better quality of life for patients, while both treatments had similar overall survival rates and adverse event profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial. Kim, ST., Kang, JH., Lee, J., et al.[2023]

In a study of 65 patients with advanced biliary system adenocarcinomas, the combination therapy of capecitabine and oxaliplatin (CAPOX) showed a 27% response rate in patients with gallbladder carcinoma (GBC) and extrahepatic cholangiocarcinoma (ECC), indicating its efficacy for these types of cancer.

The CAPOX regimen was well tolerated overall, with the most common severe side effect being peripheral sensory neuropathy in 11 patients, suggesting it is a viable treatment option for advanced GBC and ECC, but less effective for intrahepatic cholangiocarcinoma (ICC), which had no objective responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial. Nehls, O., Oettle, H., Hartmann, JT., et al.[2022]

In a network meta-analysis of 16 trials with 2245 patients, the combination of Gemcitabine and S-1 (GS) showed superior efficacy in terms of overall survival and response rates compared to standard treatments like Fluorouracil (FU).

While GS and other combinations like Cap plus CIS (CapC) demonstrated better response rates, they also had higher incidences of severe side effects, highlighting the need for careful consideration of both efficacy and toxicity when choosing treatment options for advanced biliary tract cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of First-line Chemotherapies for Advanced Biliary Tract Cancer: A Network Meta-analysis. Zheng, W., Ying, J., Zhou, Y., et al.[2020]

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 combination of nab-paclitaxel and S-1 demonstrated a 27.5% objective response rate in patients with advanced biliary tract carcinoma, indicating significant antitumor activity, especially in gallbladder carcinoma (53.8% response).

The treatment showed a favorable safety profile, with the most common severe side effects being neutropenia and stomatitis, and median progression-free survival and overall survival were 6.0 months and 13.2 months, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel plus tegafur gimeracil oteracil potassium capsule (S-1) as first-line treatment for advanced biliary tract adenocarcinoma: a phase 2 clinical trial. Zhang, W., Sun, Y., Jiang, Z., et al.[2023]

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 of 33 patients with relapse and unresectable biliary tract cancer treated with S-1 after failing gemcitabine, the neutrophil-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) were identified as significant poor prognostic factors for overall survival.

Changes in the PNI from the start of S-1 treatment to the end were significantly associated with therapeutic efficacy, suggesting that monitoring PNI could help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of Prognostic Factors in Patients with Relapse and Unresectable Biliary Tract Cancer, Treated with S-1 after Failure of Gemcitabine]. Nakai, M., Kikkawa, A., Funahara, H., et al.[2022]

The Folfox-4 chemotherapy regimen showed a significant improvement in overall survival (OS) for patients with advanced biliary tract cancer (BTC) compared to best supportive care, with a hazard ratio of 3.4 based on a network meta-analysis of 25 studies involving 3,312 individuals.

While targeted therapies generally improved progression-free survival (PFS) and objective response rates (ORR), they did not significantly enhance overall survival, with E-GEMOX showing the best ORR compared to best supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of Different Chemotherapy Regimens for Advanced Biliary Tract Cancer: A Systematic Review and Network Meta-Analysis. Li, Y., Zhou, Y., Hong, Y., et al.[2020]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4080

First-line rilvegostomig (rilve) plus chemotherapy (CTx) in ... Conclusions: Rilve plus CTx demonstrated promising efficacy with a manageable safety profile and sustained target engagement. Longer follow-up ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06109779

Study Details | NCT06109779 | Rilvegostomig + ... A global study to assess the efficacy and tolerability of rilvegostomig compared to placebo in combination with investigator's choice of chemotherapy in ...

3. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D781PC00001

Phase 3 Study of T-DXd and Rilvegostomig versus SoC in ... The purpose of this study is to measure the efficacy and safety of T-DXd with rilvegostomig or T-DXd monotherapy compared with gemcitabine plus cisplatin ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2949819824000530

New perspectives in biliary tract cancers This review aims to give a concise overview of the current available treatment options for BTC, including a short summary of longstanding therapeutic ...

5. cholangiocarcinomaaustralia.org cholangiocarcinomaaustralia.org/defeating-biliary-tract-cancer-with-artemide-biliary01-a-new-hope/

Defeating Biliary Tract Cancer with ARTEMIDE-Biliary01 By using these methods, Rilvegostomig helps convert cold tumors into hot tumors, making them more susceptible to immune-based therapies. This ...

6. ccanewsonline.com ccanewsonline.com/issues/2025/september-2025-vol-6-no-3/rilvegostomig-plus-chemotherapy-in-advanced-biliary-tract-cancer

Rilvegostomig Plus Chemotherapy in Advanced Biliary ... Real-world data from US veterans confirm the safety and efficacy of ivosidenib in treating IDH1-mutated cholangiocarcinoma, offering hope for improved outcomes ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS4199

A phase 3, randomized study of adjuvant rilvegostomig ... This study will enroll approximately 750 adults with histologically confirmed adenocarcinoma of the biliary tract (intrahepatic or extrahepatic ...