A Phase II Study of Ivonescimab in Combination With GEMOX as Neoadjuvant and Conversion Therapy for Biliary Tract Cancer

NCT07854600 | Recruiting Phase 2

• 1 other identifier: XH-LW-2026-007
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to explore the efficacy and safety of Ivonescimab in combination with GEMOX chemotherapy as neoadjuvant and conversion therapy for patients with biliary tract cancer. It aims to evaluate the impact of this combination regimen on postoperative recurrence, patient survival, and medication safety. This is a single-center, phase II, interventional, single-arm, multi-cohort clinical study. A total of 87 eligible participants will be enrolled and assigned to either the neoadjuvant therapy cohort (45 participants) or the conversion therapy cohort (42 participants).

Conditions

Biliary Tract Cancer (BTC)

Keywords

Ivonescimab; Neoadjuvant Therapy; Conversion Therapy; Biliary Tract Cancer; GEMOX Regimen

Outcome Measures

Primary Outcomes (2)

• R0 Resection Rate

  The proportion of participants in the neoadjuvant therapy cohort who undergo surgical resection and achieve microscopically margin-negative (R0) resection.

  Up to 6 weeks post-surgery

• Objective Response Rate

  The proportion of participants in the conversion therapy cohort achieving a Complete Response (CR) or Partial Response (PR) based on RECIST v1.1 criteria as assessed by investigators.

  Up to 24 weeks (assessed after 3-6 cycles of treatment)

Secondary Outcomes (9)

• Objective Response Rate

  Up to 10 weeks from baseline (assessed pre-operatively)

• R0 Resection Rate

  Up to 4 weeks post-surgery (assessed upon availability of postoperative pathology report)

• Pathological Response Rate

  Up to 4 weeks post-surgery

• Disease Control Rate

  Up to 19 weeks from baseline (assessed pre-operatively)

• Incidence and Severity of Adverse Events

  Up to 28 days after the last dose of study treatment

Study Arms (1)

Ivonescimab + GEMOX

EXPERIMENTAL

Participants in both the neoadjuvant therapy cohort and the conversion therapy cohort belong to this single experimental arm. All participants will receive 3 to 6 cycles of Ivonescimab in combination with GEMOX chemotherapy prior to surgical evaluation.

Drug: Ivonescimab; Drug: GEMOX Regimen

Interventions

Ivonescimab DRUG

Administered at a dose of 20 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) in combination with GEMOX chemotherapy for 3 to 6 cycles. For eligible patients in the conversion therapy cohort who do not undergo surgery after evaluation, Ivonescimab is continued as maintenance monotherapy (20 mg/kg, IV, Q3W, Day 1) until disease progression, unacceptable toxicity, death, withdrawal of consent, or investigator decision.

Also known as: AK112

Ivonescimab + GEMOX

GEMOX Regimen DRUG

The GEMOX regimen consists of Gemcitabine (1000 mg/m²) and Oxaliplatin (100 mg/m²). Both drugs are administered via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). This chemotherapy regimen is administered in combination with Ivonescimab for 3 to 6 cycles prior to surgical evaluation.

Also known as: Gemcitabine and Oxaliplatin

Ivonescimab + GEMOX

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Subjects voluntarily participate in the study, agree to sign a written informed consent form, demonstrate good compliance, and are willing to cooperate with follow-up.
• \. Male or female aged \>= 18 and \<= 80 years at the time of signing the ICF.
• \. Histologically or cytologically confirmed biliary tract cancer (BTC, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer), and radiologically assessed as locally advanced or with oligometastases (defined as Stage IIIA or higher lesions according to the 8th edition of the AJCC staging system). Subjects must agree to provide archived or fresh tumor biopsy specimens and peripheral blood samples for biomarker testing.
• \. Lesion assessment meets one of the following conditions:
• Neoadjuvant Therapy Cohort: The tumor is graded as locally advanced with no distant metastasis, and theoretically can achieve radical resection through complex resection combined with vascular reconstruction, but both the surgical risk and postoperative recurrence risk are high (single tumor diameter \> 5 cm; imaging suggests vascular invasion or hilar lymph node metastasis; tumor number \> 3 or any single tumor \> 3 cm; preoperative CA19-9 \> 37 U/mL or exceeding the upper limit of normal \[applicable to centers where the normal range is not \< 37 U/mL\]).
• Conversion Therapy Cohort: The tumor is graded as locally advanced, unresectable, or combined with oligometastatic status (oligometastasis is defined as: metastatic lesions confined to a single organ or specific regional lymph nodes, and the number of metastatic lesions is \<= 5), with the possibility of achieving radical resection of the primary lesion and no evidence of disease (NED) status for metastatic lesions after comprehensive treatment.
• \. At least one measurable lesion (according to RECIST v1.1 criteria, the longest diameter of the measurable lesion on spiral CT scan \>= 10 mm or the shortest diameter of enlarged lymph nodes \>= 15 mm).
• \. No prior systemic therapy for biliary tract cancer.
• \. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
• \. Child-Pugh class A liver function.
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L, platelet count \>= 90 x 10\^9/L, hemoglobin \>= 90 g/L; AST and ALT \<= 3 x ULN (upper limit of normal); TBil \<= 1.5 x ULN;
• Hemoglobin \> 9 g/dL without blood transfusion or use of erythropoietin within the past 14 days;
• Serum creatinine \<= 1.5 x ULN and creatinine clearance rate (calculated using Cockcroft-Gault formula) \>= 60 ml/min;
• Good coagulation function, International Normalized Ratio (INR) \<= 1.2 or Prothrombin Time (PT) \<= 1.2 x ULN;
• Normal thyroid function, defined as Thyroid Stimulating Hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects with total T3 (or FT3) and FT4 within the normal range are also eligible;

You may not qualify if:

• \. Diagnosed with mixed periampullary cancer, or mixed hepatocellular-cholangiocarcinoma.
• \. Prior systemic anti-tumor therapy for BTC.
• \. Prior treatment with gemcitabine-based chemotherapy, platinum-based chemotherapy, or any tumor immunotherapy/targeted therapy (e.g., PD-1/PD-L1 inhibitors, VEGF inhibitors, etc.).
• \. History of severe allergy to other monoclonal antibodies. Known severe allergy or intolerance to gemcitabine, platinum drugs, or any of their components/excipients.
• \. Known allergy or intolerance to recombinant humanized PD-1 monoclonal antibody drugs, VEGF monoclonal antibody drugs, and their components (or any excipients), or a history of severe allergy to other monoclonal antibodies.
• \. Pericardial effusion, uncontrollable pleural effusion, or clinically significant ascites within 7 days prior to treatment, defined as meeting the following criteria: (a) ascites detectable by physical examination during the screening period, or (b) ascites requiring therapeutic paracentesis during the screening period.
• \. Clinical evidence of portal hypertension with esophageal or gastric varices within 6 months prior to the start of treatment.
• \. Any bleeding or thrombotic disorders within 6 months prior to the start of treatment, or currently taking any anticoagulants (e.g., warfarin or similar drugs) requiring monitoring of the International Normalized Ratio (INR) during treatment.
• \. History of any malignant tumor, except for the BTC studied in this clinical trial and cured locally recurrent cancers (e.g., resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical cancer or breast cancer in situ, occult thyroid cancer).
• \. Known central nervous system metastasis and/or leptomeningeal disease prior to treatment.
• \. History of any active immunodeficiency or autoimmune disease, and/or any immunodeficiency or autoimmune disease that may relapse at the time of screening.
• \. Any severe chronic or active infection (except viral hepatitis) requiring systemic antibacterial, antifungal, or antiviral therapy (e.g., tuberculosis) prior to the start of treatment.
• \. Electrocardiogram (ECG) during screening shows a heart rate-corrected QT interval (QTc) (corrected using Fridericia's formula) exceeding 450 milliseconds. Note: If the QTc interval exceeds 450 milliseconds on the first ECG, a repeat ECG will be performed to confirm the result.
• \. Presence of any of the following cardiovascular risk factors: cardiogenic chest pain within 28 days prior to treatment, defined as moderate pain limiting activities of daily living (ADL); symptomatic pulmonary embolism within 28 days prior to treatment; acute myocardial infarction within 6 months prior to treatment; history of New York Heart Association (NYHA) Class III or IV heart failure within 6 months prior to treatment; Grade \>= 2 ventricular arrhythmia within 6 months prior to treatment; cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to treatment.
• \. Organ transplantation or hematopoietic stem cell transplantation (HSCT) or any major surgery within 28 days prior to treatment.

Sponsors & Collaborators

• Haitao Zhao, MD: lead

Study Sites (1)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

gemcitabine-oxaliplatin regimen; Gemcitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Central Study Contacts

Haitao Zhao, DR

CONTACT

+86-10-69156042; zhaoht@pumch.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director, Department of Hepatic Surgery

Study Record Dates

• First Submitted: September 24, 2026
• First Posted: October 2, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)