A Randomised, Phase II Trial to Evaluate the Efficacy of Ivonescimab, a PD 1/VEGF Bispecific Antibody, Versus FOLFOX as Second Line Therapy for Locally Advanced/Metastatic Biliary Cancers
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- UNICANCER
- Enrollment
- 72
- Locations
- 3
- Primary Endpoint
- Progression-free survival (PFS)
Overview
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.
Detailed Description
This is a Phase 2, multicentre, randomised, two-arm, open-label trial to evaluate whether ivonescimab is superior to standard second-line chemotherapy in the treatment of patients with advanced biliary tract cancer.
The trial will be open to patients who participated in the screening phase of the SAFIR-ABC10 protocol (NCT05615818) and who experienced disease progression on or following the first-line standard of care (CISGEM regimen).
A total of 72 patients will be enrolled and randomly assigned (2:1) to receive treatment with either:
- Experimental arm: Ivonescimab 20 mg/kg by intravenous infusion (IV) once every 3 weeks (Q3W).
- Control arm: Standard second-line chemotherapy - FOLFOX regimen Response to treatment will be assessed according to RECIST v1.1 by radiographic exams performed every 42 (±7) days. Patients will continue treatment until disease progression or for a maximum of 34 cycles of ivonescimab (experimental arm), whichever occurs first.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •Presence of at least one evaluable lesion according to RECIST v1.
- •Age ≥18 years.
- •Adequate bone marrow function: absolute neutrophil count (ANC) ≥2 × 10⁹/L, platelet count ≥100 × 10⁹/L, and haemoglobin ≥9 g/dL.
Exclusion Criteria
- •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.
Arms & Interventions
Experimental
Experimental treatment under study
Intervention: Ivonescimab (Drug)
Control
Standard of care second-line treatment for advanced biliary tract cancer
Intervention: FOLFOX regimen (Drug)
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: From randomisation to disease progression or death, up to 4 years
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.
Secondary Outcomes
- 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)