Testing Ivonescimab Versus FOLFOX in Advanced Biliary Tract Cancer Patients

NCT06529718 | Recruiting Phase 2 DMC

• 2 other identifiers: UC-GIG-2404 - PRODIGE 1102024-515875-36-00
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 3

Brief Summary

The object of this trial is to test whether ivonescimab is superior to standard chemotherapy (FOLFOX regimen) for the treatment of patients with advanced biliary tract cancer after failure of a first line of chemotherapy. It is only open to patients who participated in the SAFIR-ABC10 trial (NCT05615818) but did not receive experimental treatment. Eligible patients will be randomised (2:1) to receive either ivonescimab or FOLFOX. Treatment will be continued until disease progression, or a maximum of 34 cycles of ivonescimab (experimental arm), whichever occurs first.

Conditions

Biliary Tract Cancer

Keywords

Biliary tract cancer; Gallbladder; Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.

  From randomisation to disease progression or death, up to 4 years

Secondary Outcomes (4)

• Overall Survival (OS)

  From randomisation to death, up to 4 years

• Objective response rate

  From randomisation, up to 4 years

• Disease control rate

  From randomisation, up to 4 years

• Duration of response

  From response to disease progression or death, up to 5 years

Other Outcomes (3)

• Quality of life questionnaire - Core 30 (QLQ-C30)

  From baseline, every 2 cycles (every 4-6 weeks) until end of treatment, an average of 1 year

• Quality of life Questionnaire - Biliary tract cancer module (QLQ-BIL21)

  From baseline, every 2 cycles (every 4-6 weeks) until end of treatment, an average of 1 year

• Incidence of Adverse Events

  From randomisation, up to 4 years

Study Arms (2)

Experimental

EXPERIMENTAL

Experimental treatment under study

Drug: Ivonescimab

Control

ACTIVE COMPARATOR

Standard of care second-line treatment for advanced biliary tract cancer

Drug: FOLFOX regimen

Interventions

Ivonescimab DRUG

20 mg/kg IV infusion every 3 weeks

Experimental

FOLFOX regimen DRUG

oxaliplatin 85 mg/m² IV, leucovorin 200 mg/m² IV (or folinic acid 400 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m² as a 46 hour continuous IV infusion, every 2 weeks

Control

Eligibility Criteria

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

You may qualify if:

• Signed a written informed consent form prior to any trial specific procedures.
• Histologically-proven intrahepatic cholangiocarcinoma, perihilar / distal cholangiocarcinoma, or gallbladder carcinoma (ampullary carcinoma excluded).
• Locally advanced (non-resectable) or metastatic disease.
• Participated in the Screening phase of the SAFIR-ABC10 trial.
• Progression after first line standard of care (1L-SoC) regimen (CISGEM ± immunotherapy) as assessed by the investigator.
• Eligible for second-line treatment with FOLFOX.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Presence of at least one evaluable lesion according to RECIST v1.1.
• Age ≥18 years.
• Adequate bone marrow function: absolute neutrophil count (ANC) ≥2 × 10⁹/L, platelet count ≥100 × 10⁹/L, and haemoglobin ≥9 g/dL.
• Note: Blood transfusion or growth factor therapy should not be performed within 7 days prior to the screening haematology analysis.
• Adequate liver function: total bilirubin level ≤1.5 × the upper limit of normal (ULN) range (≤3 x ULN for patients with liver metastases or confirmed/suspected Gilbert syndrome, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤2.5 × ULN (AST and ALT ≤5 x ULN when documented liver metastasis).
• Adequate renal function: estimated creatinine clearance ≥50 mL/min according to the Cockcroft-Gault formula, or estimated glomerular filtration rate value ≥50 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and urine protein \< 2+ or 24 hour urine protein quantification \< 1.0 g.
• Coagulation: prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 x ULN, and partial prothrombin time (PTT) or activated PTT ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy,or prophylactic coagulation).
• Adequate cardiac function: left ventricular ejection fraction (LVEF) ≥50% at baseline as determined by either echocardiogram or multigated acquisition (MUGA) scan.

You may not qualify if:

• Toxicities from 1L-SoC not resolved to Grade ≤ 1 (according to version 5.0 of the National Cancer Institute - Common terminology criteria for adverse events \[NCI-CTCAE v5.0\]) before randomisation with the exception of alopecia.
• Received first-line maintenance therapy with a matched target therapy proposed in SAFIR ABC10, or any second-line treatment.
• Contraindication to ivonescimab.
• Proven complete deficiency of dihydropyrimidine dehydrogenase (DPD).
• Treatment with brivudine, sorivudine or their chemical analogues in the 4 weeks prior to randomisation.
• Major surgical procedures or serious trauma within 4 weeks prior to randomisation, or plans for major surgery within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterisation and port implantation) within 3 days prior to randomisation.
• History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to randomisation, including but not limited to:
• Gastrointestinal bleeding.
• Haemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots).
• Note: transient haemoptysis associated with diagnostic bronchoscopy is allowed.
• Nasal bleeding /epistaxis (bloody nasal discharge is allowed).
• Need for therapeutic anticoagulant therapy within 14 days prior to randomization.
• Note: Prophylactic anticoagulation for deep vein thrombosis or pulmonary embolism or to maintain venous patency is allowed.
• Current hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy.
• History of major diseases before randomization, specifically:

Sponsors & Collaborators

• UNICANCER: lead
• Cancer Research UK & UCL Cancer Trials Centre: collaborator
• Belgian Group of Digestive Oncology: collaborator
• Summit Therapeutics: collaborator

Study Sites (3)

Institute Mutualiste Montsouris

Paris, France

NOT YET RECRUITING

Centre Eugène Marquis

Rennes, France

RECRUITING

University College London

London, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms; Cholangiocarcinoma

Interventions

Folfox protocol

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

Study Officials

• Julien Edeline, MD

  Centre Eugène Marquis

  PRINCIPAL INVESTIGATOR

• Ivan Borbath, MD

  Cliniques universitaires Saint-Luc- Université Catholique de Louvain

  PRINCIPAL INVESTIGATOR

• John Bridgewater, MD

  University College London Cancer Institute

  PRINCIPAL INVESTIGATOR

• David Malka, MD

  Institut Mutualiste Montsouris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel Couch

CONTACT

+33 (0)1 80 50 12 96; d-couch@unicancer.fr

Study Design

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

Study Record Dates

• First Submitted: July 26, 2024
• First Posted: July 31, 2024
• Study Start: October 9, 2025
• Primary Completion (Estimated): August 3, 2027
• Study Completion (Estimated): January 30, 2029
• Last Updated: November 17, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.
• Access Criteria: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.

Locations

GB (1); FR (2)