NCT07269158

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

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 160 (estimated)
• Sponsor: Yonsei University · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This phase IIb randomized trial assesses the efficacy and safety of immune checkpoint inhibitor (ICI) monotherapy versus ICI-based combination maintenance therapy with lenvatinib, venadaparib, or SLC-3010 in advanced biliary tract cancer. Durvalumab (q4w) or pembrolizumab (q3w) serve as backbone ICIs. For each group, Lenvatinib is given orally once daily, venadaparib orally, or SLC-3010 as a 60-minute IV infusion. Recommended phase II doses will be established via a 3+3 dose-escalation design, with toxicity management per NCI-CTCAE v5.0.

Conditions

• Biliary Tract Neoplasms
• Advanced Cancer
• Immunotherapy

Interventions

Type	Name	Description
DRUG	Durvalumab or Pembrolizumab	Phase 2 Durvalumab 1500mg IV D1, q 4weeks or Pembrolizumab 200mg IV D1, q 3weeks
DRUG	Durvalumab or Pembrolizumab + Levnatinib	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
DRUG	Durvalumab or Pembrolizumab + Venadaparib	Durvalumab or Pembrolizumab + Venadaparib
DRUG	Durvalumab or Pembrolizumab + SCL-3010	Durvalumab or Pembrolizumab + SCL-3010

Timeline

• Start date: 2025-12-01
• Primary completion: 2029-09-01
• Completion: 2029-09-01
• First posted: 2025-12-08
• Last updated: 2025-12-08

Locations

1 site across 1 country: South Korea