Ivonescimab in Combination With Liposomal Irinotecan and 5-FU/LV in Potentially Resectable Biliary Tract Malignancies

NCT06993025 | Not Yet Recruiting Phase 2

• 1 other identifier: EC-2025-004
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This Phase II, single-arm, single-center study evaluates the conversion to resectability and safety of Ivonescimab combined with liposomal irinotecan and 5-FU/LV in patients with potentially resectable biliary tract malignancies. Eligible patients receive three cycles of the combination therapy every 3 weeks, followed by surgery. Post-surgery, patients resume treatment for three more cycles and then continue with evoracizumab alone for up to 1 year. Safety is monitored through AE and SAE assessments for at least 30 and 90 days post-last dose, respectively. Biomarker exploration is also conducted in consenting patients.

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• surgical conversion success rate

  Surgical conversion success rate refers to the percentage of subjects who achieve relief after treatment and undergo surgical treatment among the evaluable cases, while also calculating the R0 resection rate and the relief situation based on postoperative pathology.

  From the start of conversion therapy until surgical evaluation or resection, or until it is determined that surgical resection is not feasible.

Study Arms (1)

Ivonescimab+chemotherpy

EXPERIMENTAL

After signing informed consent, subjects who meet the inclusion criteria following screening will receive Ivonescimab in combination with irinotecan liposome injection and 5-FU/LV, administered every 3 weeks for 3 cycles, followed by scheduled radical surgery. Subjects who achieve successful conversion will resume treatment within 8 weeks after surgery and continue with Ivonescimab in combination with irinotecan liposome injection and 5-FU/LV, administered every 3 weeks for 3 cycles. Subsequently, they will receive Ivonescimab monotherapy until 1 year of treatment is completed. Dosing Schedule: 1. Ivonescimab: 20 mg/kg, Day 1, intravenous infusion (ivgtt), every 3 weeks (Q3W). 2. Irinotecan Liposome: 70 mg/m², Day 1, intravenous infusion (ivgtt), every 3 weeks (Q3W). 3. Calcium Folinate (LV): 400 mg/m², Day 1, intravenous infusion (ivgtt), every 3 weeks (Q3W). 4. 5-FU: 2400 mg/m², Day 1, intravenous infusion (ivgtt), every 3 weeks (Q3W).

Drug: Ivonescimab+chemotherapy

Interventions

Ivonescimab+chemotherapy DRUG

Dosing Schedule: 1. Ivonescimab: 20 mg/kg, Day 1, intravenous infusion (ivgtt), every 3 weeks (Q3W). 2. Irinotecan Liposome: 70 mg/m², Day 1, intravenous infusion (ivgtt), every 3 weeks (Q3W). 3. Calcium Folinate (LV): 400 mg/m², Day 1, intravenous infusion (ivgtt), every 3 weeks (Q3W). 4. 5-FU: 2400 mg/m², Day 1, intravenous infusion (ivgtt), every 3 weeks (Q3W).

Also known as: Ivonescimab+Liposomal Irinotecan + 5-FU/LV

Ivonescimab+chemotherpy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent: Able to provide written informed consent and understand and agree to comply with study requirements and the assessment schedule.
• Age and Gender: Age ≥18 years and ≤75 years on the day of signing the Informed Consent Form (ICF), male or female.
• Disease Status: Potentially resectable, previously untreated biliary tract malignancy confirmed by histological or cytological evidence.
• Tumor Assessment: Tumor evaluated by a hepatobiliary surgeon with sufficient objective evidence to determine irresectability.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life Expectancy: Estimated survival of more than 12 weeks.
• Body Weight: Weight \>30 kg.
• Prior Therapy: No prior anti-tumor therapy, including but not limited to anti-CTLA-4, anti-VEGF, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies.
• EnEnough Organ Function
• Coagulation: Prothrombin time (PT) ≤1.5×ULN, international normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (aPTT) ≤1.5×ULN.
• Blood Pressure: Systolic blood pressure ≤150 mmHg and diastolic blood pressure ≤90 mmHg during the screening period, with or without antihypertensive medication. No changes to antihypertensive therapy within 1 week prior to the first administration of the study drug.
• Contraception: Sexually active males and females of childbearing potential (not surgically sterilized) must agree to use a medically accepted method of contraception (e.g., intrauterine device, contraceptive pill, or condom) during the study treatment period and for 6 months after the last dose of study treatment.
• Females of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-HCG) test within 7 days prior to study enrollment and must not be breastfeeding.
• HBV Management: Patients with detectable HBV DNA levels (≥10 IU/mL or above the limit of detection) and HBV infection (defined as positive hepatitis B surface antigen \[HBsAg\] and/or hepatitis B core antibody \[anti-HBc\]) must receive antiviral therapy according to clinical practice prior to study treatment to ensure adequate viral suppression. Antiviral therapy must be continued during the study period and for 6 months after the last dose of study treatment. Patients with positive anti-HBc but undetectable HBV DNA (\<10 IU/mL or below the limit of detection) do not require antiviral therapy unless HBV DNA exceeds 10 IU/mL or the limit of detection during the study. Patients with active HBV and HCV co-infection (defined by positive anti-HCV antibody) or active HBV and hepatitis D virus co-infection are excluded.
• Voluntary Participation: Willing to voluntarily participate in the clinical trial, comply with study visits and procedures, understand the study requirements, and have signed the informed consent form.

You may not qualify if:

• Participants with any of the following conditions are not eligible for this study:
• Presence of unresectable extrahepatic metastases.
• Prior treatment for cholangiocarcinoma, including chemotherapy, molecularly targeted agents, traditional Chinese medicine with antitumor properties, radiotherapy, or interventional therapy (excluding percutaneous transhepatic cholangial drainage \[PTCD\] or common bile duct stenting). This also includes prior immunotherapy for cholangiocarcinoma.
• History of allogeneic organ transplantation.
• Major surgery, active ulceration, or incomplete wound healing within 1 month prior to the first administration of the study drug (excluding central venous catheter placement, tumor biopsy, or nasogastric tube insertion).
• Planned elective surgery during the study period.
• Blood product transfusion or administration of hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF, M-CSF) within 14 days prior to the first dose of the study drug.
• Live-attenuated vaccine administration within 30 days prior to the first dose of the study drug.
• Use of immunosuppressive medications within 14 days prior to the first dose. Exceptions include:
• Topical, inhaled, or intra-articular corticosteroids.
• Systemic corticosteroid doses ≤10 mg/day of prednisone or equivalent.
• Prophylactic corticosteroid use for hypersensitivity reactions (e.g., premedication for CT scans).
• Active autoimmune or inflammatory diseases, or a history thereof, including inflammatory bowel disease (e.g., colitis, Crohn's disease), diverticulitis (excluding diverticulosis), systemic lupus erythematosus, sarcoidosis, Wegener's syndrome, granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, or uveitis. Exceptions include:
• Vitiligo or alopecia.
• Stable hypothyroidism managed with hormone replacement (e.g., post-Hashimoto's thyroiditis).

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (2)

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

Tianjin Cancer Hospital Airport Hospital

Tianjin, Tianjin Municipality, 300308, China

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Central Study Contacts

Lu chen, MD

CONTACT

（022）60670123-5202; tjchlhk@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2025
• First Posted: May 28, 2025
• Study Start: May 25, 2025
• Primary Completion: April 25, 2026
• Study Completion (Estimated): April 25, 2027
• Last Updated: May 28, 2025

Record last verified: 2025-04

Locations

CN (2)