"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.
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 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.
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.
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.
Parallel
Durvalumab or Pembrolizumab
DrugPhase 2 Durvalumab 1500mg IV D1, q 4weeks or Pembrolizumab 200mg IV D1, q 3weeks
Durvalumab or Pembrolizumab + Levnatinib
DrugDurvalumab 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
Durvalumab or Pembrolizumab + Venadaparib
DrugDurvalumab or Pembrolizumab + Venadaparib
Durvalumab or Pembrolizumab + SCL-3010
DrugDurvalumab or Pembrolizumab + SCL-3010
Phase Ib: Recommended Phase II Dose
Recommended Phase II Dose decided during DLT periods
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.
Objective response rate, ORR
Objective response rate (ORR) is the proportion of patients achieving complete response (CR) or partial response (PR) per RECIST 1.1.
Overall Survival, OS
Overall survival (OS) is defined as the time interval from cycle 1 day 1 to death from any cause or last follow-up.
Disease Control Rate, DCR
Disease control rate (DCR) is the proportion of patients with CR, PR, or stable disease (SD) per RECIST 1.1.
Duration of Response, DOR
Duration of response (DOR) is defined as the time interval from the first documented response (CR or PR) per RECIST 1.1 to tumor progression, death, or last follow-up.
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