A Phase IIb Randomized Clinical Trial of Immune Checkpoint Inhibitor-based Maintenance Therapy in Patients With Advanced Biliary Tract Cancer

NCT07269158 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 4-2025-1249
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

"Biliary tract cancer (BTC) is a rare malignancy with a poor prognosis. Most patients present with unresectable disease, and even after curative-intent resection, recurrence is common. Since the ABC-02 trial, gemcitabine plus cisplatin (Gem/Cis) has been established as the standard first-line regimen, but the median overall survival (OS) remains approximately 11.7 months. Recent studies combining immune checkpoint inhibitors (ICIs) such as durvalumab or pembrolizumab with Gem/Cis have improved OS to 12.7-12.9 months, establishing ICI-based combination therapy as the new standard. However, the optimal maintenance therapy following initial chemoimmunotherapy remains undefined. This phase IIb study enrolls patients with advanced BTC who achieved disease control after at least eight cycles of Gem/Cis plus ICI. The trial compares the efficacy and safety of ICI monotherapy maintenance versus ICI in combination with lenvatinib, venadaparib, or interleukin-2 (IL-2, SLC-3010). Lenvatinib, through inhibition of FGFR2 and modulation of the tumor immune microenvironment, is expected to enhance ICI efficacy. PARP inhibitors may be beneficial in patients with homologous recombination deficiency (HRD) or platinum-sensitive disease. Additionally, IL-2 can activate tumor-infiltrating lymphocytes and alleviate the immunosuppressive microenvironment, potentially augmenting ICI responsiveness. This study aims to explore a novel maintenance strategy integrating molecular targeted therapy, DNA damage repair modulation, and cytokine-based immunotherapy to overcome the limitations of current ICI monotherapy in BTC. The combination approach is expected to improve disease control and survival outcomes in patients with advanced BTC.

Conditions

Immunotherapy; Biliary Tract Neoplasms; Advanced Cancer

Keywords

Biliary Tract Neoplasms [including Intrahepatic Cholangiocarcinoma, Extrahepatic Cholangiocarcinoma, and Gallbladder Neoplasms]

Outcome Measures

Primary Outcomes (2)

• Phase Ib: Recommended Phase II Dose

  Recommended Phase II Dose decided during DLT periods

  Up to 4 years

• Phase II: Progression Free Survival(PFS)

  Progression-free survival (PFS) is the length of time from the start of treatment until the disease progresses or the patient dies from any cause, whichever occurs first.

  Up to 4 years

Secondary Outcomes (7)

• Objective response rate, ORR

  Up to 4 years

• Overall Survival, OS

  Up to 4 years

• Disease Control Rate, DCR

  Up to 4 years

• Duration of Response, DOR

  Up to 4 years

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Up to 4 years

Study Arms (4)

Immunotherapy Maintenance

EXPERIMENTAL

Durvalumab or Pembrolizumab

Drug: Durvalumab or Pembrolizumab

Immunotherapy Maintenance + Lenvatinib

ACTIVE COMPARATOR

Durvalumab or Pembrolizumab + Levnatinib

Drug: Durvalumab or Pembrolizumab + Levnatinib

Immunotherapy Maintenance + Venadaparib

ACTIVE COMPARATOR

Durvalumab or Pembrolizumab + Venadaparib

Drug: Durvalumab or Pembrolizumab + Venadaparib

Immunotherapy Maintenance + SCL-3010

ACTIVE COMPARATOR

Durvalumab or Pembrolizumab + SCL-3010

Drug: Durvalumab or Pembrolizumab + SCL-3010

Interventions

Durvalumab or Pembrolizumab DRUG

Phase 2 Durvalumab 1500mg IV D1, q 4weeks or Pembrolizumab 200mg IV D1, q 3weeks

Immunotherapy Maintenance

Durvalumab or Pembrolizumab + Levnatinib DRUG

Durvalumab 1500mg IV D1, q 4weeks or Pembrolizumab 200mg IV D1, q 3weeks Lenvatinib 12mg (≥60 kg) PO q 1cycle or 8mg (\<60 kg) PO q 1cycle

Immunotherapy Maintenance + Lenvatinib

Durvalumab or Pembrolizumab + Venadaparib DRUG

Durvalumab or Pembrolizumab + Venadaparib

Immunotherapy Maintenance + Venadaparib

Durvalumab or Pembrolizumab + SCL-3010 DRUG

Durvalumab or Pembrolizumab + SCL-3010

Immunotherapy Maintenance + SCL-3010

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced biliary tract cancer who have completed at least 8 cycles of Durvalumab plus Gemcitabine and Cisplatin treatment without radiologic evidence of disease progression, and are planned to receive Durvalumab maintenance therapy.
• (Patients treated with Pembrolizumab plus Gemcitabine/Cisplatin are also eligible if they are to continue Pembrolizumab monotherapy without Gemcitabine as maintenance therapy.)
• Patients who are 20 years of age or older at the time of signing the informed consent form.
• Patients with histologically confirmed biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder carcinoma.
• (Patients with neuroendocrine tumors or sarcomas are excluded.)
• Patients who are willing and able to provide written informed consent for participation in the study.
• Patients with measurable disease according to RECIST version 1.1.
• ECOG performance status of 0 or 1.
• Estimated life expectancy ≥ 3 months.
• Patients with adequate organ and bone marrow function, without transfusion or administration of hematopoietic growth factors (e.g., G-CSF) within 2 weeks prior to treatment initiation, defined as follows:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
• Platelet count ≥ 75 × 10⁹/L
• Serum creatinine ≤ 1.5 × upper limit of normal (ULN), or estimated creatinine clearance ≥ 45 mL/min (calculated using the Cockcroft-Gault formula; see Appendix 7)
• AST and ALT ≤ 3.0 × ULN (≤ 5.0 × ULN if liver metastases are present)

You may not qualify if:

• Patients who have received more than 10 cycles of immune checkpoint inhibitor (ICI) plus Gemcitabine and Cisplatin combination therapy for advanced biliary tract cancer.
• Patients who have been treated for, or have evidence of recurrence or progression of, any malignancy other than biliary tract cancer within the past 3 years.
• Exceptions: Patients who have been disease-free for ≥3 years after curative treatment, or patients with the following malignancies are not excluded: basal cell carcinoma of the skin, Stage I squamous cell carcinoma of the skin, carcinoma in situ, intramucosal carcinoma, or superficial bladder carcinoma.
• Patients with residual adverse events from prior therapy or surgery that may interfere with the safety evaluation of the investigational product.
• Patients with a history of hypersensitivity to any component of monoclonal antibody products.
• Patients with a history or evidence of active, non-infectious interstitial lung disease (pneumonitis).
• Patients with symptomatic or clinically active brain or leptomeningeal metastases requiring treatment.
• (Patients with asymptomatic, stable, and untreated brain metastases may be enrolled.)
• Patients who are immunodeficient or are receiving systemic corticosteroids or other immunosuppressive therapy within 7 days prior to the first dose of the investigational product.
• (Physiologic doses of corticosteroids, such as for acute asthma exacerbation, may be allowed after consultation with the principal investigator.)
• Patients with uncontrolled or significant cardiovascular disease, defined as any of the following:
• Myocardial infarction within 180 days prior to randomization
• Uncontrolled angina within 180 days prior to randomization
• Congestive heart failure classified as New York Heart Association (NYHA) Class III or IV
• Uncontrolled hypertension despite appropriate therapy (systolic ≥150 mmHg or diastolic ≥90 mmHg for \>24 hours)

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Division of Medical Oncology, Yonsei Cancer Center, Yonsei Univ. College of Medicine, Korea

Seoul, South Korea

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms; Cholangiocarcinoma; Gallbladder Neoplasms

Interventions

durvalumab; pembrolizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Gallbladder Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: December 8, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: December 8, 2025

Record last verified: 2025-11

Locations

KR (1)