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Locally Advanced Biliary Tract AdenocarcinomaPhase 2/3NCT07765433

Testing the Addition of Ivonescimab Combined With Standard Chemotherapy Compared to the Usual Chemotherapy and Immunotherapy Treatment for Patients With Advanced Biliary Tract Cancer

A Phase 2/3 study testing Biospecimen Collection, Cisplatin and Computed Tomography in people with Locally Advanced Biliary Tract Adenocarcinoma and Locally Advanced Extrahepatic Cholangiocarcinoma, run by ECOG-ACRIN Cancer Research Group.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
Search all trials

Trial summary

This phase II/III trial studies how well the addition of ivonescimab to standard chemotherapy (gemcitabine and cisplatin) works when compared to usual chemotherapy and immunotherapy (durvalumab or pembrolizumab) in treating patients with biliary tract cancer that may have spread from where it first started to nearby… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Cisplatin and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
336 participants
Where
No sites listed yet
Study dates
11 Jan 2027to 31 Dec 2029
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient must be ≥ 18 years of age
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
  • Patient must have histologically or cytologically confirmed adenocarcinoma of the biliary tract including cholangiocarcinoma (intrahepatic or extrahepatic) or gallbladder carcinoma
  • Patient must not have a diagnosis of ampullary cancer
  • Patient must have documented metastatic or locally advanced unresectable disease on CT or MR imaging
  • Patient must have measurable disease as documented on CT or MRI imaging done within 28 days prior to randomization
Show all 45Show fewer
  • Patient must not have received prior systemic therapy for current metastatic or locally advanced biliary tract cancer
  • NOTE: Patients who have previously received adjuvant/neoadjuvant chemotherapy and/or radiotherapy for curative intent non-metastatic disease are eligible if they developed recurrent disease > 6 months after completion of adjuvant therapy/radiotherapy
  • Patient must not be on any systemic immunosuppressant therapy other than inhaled steroids, intranasal steroids, topical steroids or systemic steroids up to 10mg prednisone equivalent
  • Patient must not have received a live attenuated vaccine within 30 days prior to randomization. Patients must also not receive a live attenuated vaccine while on protocol treatment or up to 30 days after the last dose of protocol treatment
  • Patient must have no contraindication to VEGF inhibitor therapy
  • Patient must not have significant vascular disease (i.e., aortic aneurysm surgical repair or peripheral arterial thrombosis) within 6 months prior to randomization
  • Patient must not have inadequately controlled arterial hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure [BP] > 100 mmHg). Anti-hypertensive therapy to achieve these parameters is allowed
  • Patient must not have experienced a clinically significant bleeding event within 6 months prior to randomization
  • Patient must not have experienced gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, or intraabdominal abscess
  • Patient must not have had surgery within 30 days prior to randomization
  • Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used
  • All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy
  • A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Patients of childbearing potential must continue contraceptive measures for 6 months after the last dose of protocol treatment, with the exception of cisplatin requiring 14 months for female patients and 11 months for male patients
  • Patient must not nurse infants for 4 months after the last dose of pembrolizumab, 3 months after the last dose of durvalumab or ivonescimab and for four weeks after the last dose of cisplatin
  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  • Hemoglobin ≥ 9.0 g/dL (must be obtained ≤ 7 days prior to randomization)
  • Absolute neutrophil count (ANC) ≥ 1,500/mm^3 (must be obtained ≤ 7 days prior to randomization)
  • Platelet count ≥ 100,000/mm^3 (must be obtained ≤ 7 days prior to randomization)
  • Bilirubin ≤ 2.5 x institutional upper limit of normal (ULN) (must be obtained ≤ 7 days prior to randomization). Patients with Gilbert's syndrome must have a direct bilirubin < 1.5 mg/dL
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 × institutional ULN (must be obtained ≤ 7 days prior to randomization). For patients with liver metastases, AST and ALT ≤ 5 x ULN
  • Creatinine clearance (CrCI) > 50ml/min or calculated CrCI > 50ml/min as determined by Cockcroft-Gault (using actual body weight) Cockcroft-Gault Formula (must be obtained ≤ 7 days prior to randomization)
  • Urine dipstick for proteinuria < 2+ or 24 hour urine protein < 1.0 g (within 7 days prior to initiation of study treatment)
  • Prothrombin time (PT) or international normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1.5 X ULN (must be obtained ≤ 7 days prior to randomization). This applies only to patients who are not on therapeutic anti-coagulation. Patients receiving therapeutic anti-coagulation are eligible if on stable dose
  • Patient must not have National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade > 2 peripheral neuropathy at the time of randomization
  • Patient must not have a history of allogeneic organ transplantation
  • Patient must not have prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease such as colitis or Crohn's disease), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (i.e.: granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (i.e.: following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without an active disease in the last 5 years
  • Patients with celiac disease controlled by diet alone
  • Patients with insulin dependent diabetes
  • Patient must not have uncontrolled intercurrent illness that would limit compliance with study requirement, substantially increase the risk of incurring AEs, or compromise the ability of the patient to give written informed consent
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to randomization are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2 or better

Who cannot join

None listed.

About this study

Official title: A Phase II/III Randomized Study of Ivonescimab With Gemcitabine and Cisplatin Versus Standard of Care Chemoimmunotherapy in Advanced Biliary Tract Cancer

This phase II/III trial studies how well the addition of ivonescimab to standard chemotherapy (gemcitabine and cisplatin) works when compared to usual chemotherapy and immunotherapy (durvalumab or pembrolizumab) in treating patients with biliary tract cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as durvalumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ivonescimab is a bispecific antibody that is directed against both the programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF) protein. By targeting PD-1, ivonescimab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. By targeting VEGF, ivonescimab may help stop the formation of blood vessels that bring oxygen and nutrients to tumor. Adding ivonescimab to standard chemotherapy may work better than usual chemotherapy and immunotherapy in lowering the chance of advanced biliary tract cancer growing or spreading.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare overall survival (OS) of ivonescimab plus chemotherapy (with gemcitabine and cisplatin) versus standard of care durvalumab or pembrolizumab plus chemotherapy (with gemcitabine and cisplatin) in all randomized patients.

SECONDARY OBJECTIVES:

  1. To compare progression free survival (PFS) of ivonescimab plus chemotherapy (with gemcitabine and cisplatin) versus standard of care therapy durvalumab or pembrolizumab plus chemotherapy (with gemcitabine and cisplatin) in all randomized patients.

II. To assess additional measures of clinical activity in all randomized patients including objective response rate (ORR), duration of response, and disease control rate.

III. To assess the safety and tolerability of ivonescimab in combination with gemcitabine and cisplatin.

IV. To assess the pharmacokinetic (PK) profile of ivonescimab in combination with gemcitabine and cisplatin (GemCis).

  1. To assess the immunogenicity profile of ivonescimab in combination with GemCis.

CORRELATIVE OBJECTIVE:

  1. To perform correlative analyses on tissue and blood biospecimens collected within this trial.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive gemcitabine intravenously (IV) over 30-60 minutes and cisplatin IV on days 1 and 8 of each cycle, as well as durvalumab IV over 60 minutes or pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After cycle 8, patients receive durvalumab IV over 60 minutes or pembrolizumab IV over 30 minutes on day 1 of each cycle with or without gemcitabine IV over 30-60 minutes on days 1 and 8 of each cycle per the investigator's discretion. Cycles repeat every 21 days for up to 2 years from study treatment initiation in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) and collection of blood and urine samples throughout the study.

ARM B: Patients receive gemcitabine IV over 30-60 minutes and cisplatin IV on days 1 and 8 of each cycle, as well as ivonescimab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After cycle 8, patients receive ivonescimab IV over 60 minutes on day 1 of each cycle with or without gemcitabine IV over 30-60 minutes on days 1 and 8 of each cycle per the investigator's discretion. Cycles repeat every 21 days for up to 2 years from study treatment initiation in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and collection of blood and urine samples throughout the study.

After completion of study treatment, patients are followed every 3 months for years 0-2 from randomization and then every 6 months for years 2-3 from randomization.

Being tested
Biospecimen Collection, Cisplatin, Computed Tomography, Durvalumab, Gemcitabine Hydrochloride
Medical subject headings
Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood and urine sample collection

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • DurvalumabBiological

    Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736

    Given IV

  • Gemcitabine HydrochlorideDrug

    Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar

    Given IV

  • IvonescimabBiological

    Also called AK 112, AK-112, AK112, Anti-PD-1/Anti-VEGF Bispecific Antibody AK112

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • PembrolizumabBiological

    Also called BCD-201, GME 751, GME751, Keytruda

    Given IV

Study groups in NCT07765433
Study groupRoleWhat they receive
Arm A (gemcitabine, cisplatin, durvalumab, pembrolizumab)Active comparatorPatients receive gemcitabine IV over 30-60 minutes and cisplatin IV on days 1 and 8 of each cycle, as well as durvalumab IV over 60 minutes or pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After cycle 8, patients receive durvalumab IV over 60 minutes or pembrolizumab IV over 30 minutes on day 1 of each cycle with or without gemcitabine IV over 30-60 minutes on days 1 and 8 of each cycle per the investigator's discretion. Cycles repeat every 21 days for up to 2 years from study treatment initiation in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and collection of blood and urine samples throughout the study.
Receives: Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Biological: Durvalumab; Drug: Gemcitabine Hydrochloride; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab
Arm B (gemcitabine, cisplatin, ivonescimab)ExperimentalPatients receive gemcitabine IV over 30-60 minutes and cisplatin IV on days 1 and 8 of each cycle, as well as ivonescimab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After cycle 8, patients receive ivonescimab IV over 60 minutes on day 1 of each cycle with or without gemcitabine IV over 30-60 minutes on days 1 and 8 of each cycle per the investigator's discretion. Cycles repeat every 21 days for up to 2 years from study treatment initiation in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and collection of blood and urine samples throughout the study.
Receives: Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Gemcitabine Hydrochloride; Biological: Ivonescimab; Procedure: Magnetic Resonance Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival (OS)

    Measured: From date of randomization until the date of death from any cause, assessed up to 3 years

Secondary outcomes (7)

  1. Progression-free survival

    Will be measured per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 as assessed by the investigator.

    Measured: From the date of randomization until disease progression or death from any cause, whichever comes first, assessed up to 3 years

  2. Objective response rate

    Will be defined as the proportion of patients who have achieved best overall response of confirmed complete response (CR) or partial response (PR) to study therapy as assessed by the investigator according to RECIST v1.1.

    Measured: Up to 3 years

  3. Duration of response

    Will be measured per RECIST v1.1 as assessed by the investigator.

    Measured: From the first objective response (CR or PR) until the date of first documented disease progression or death, whichever comes first, assessed up to 3 years

  4. Disease control rate

    Will be defined as the proportion of patients who have achieved CR, PR, or stable disease for ≥ 9 weeks from date of randomization as assessed by the investigator according to RECIST v1.1.

    Measured: From 9 weeks from date of randomization up to 3 years

  5. Incidence and severity of adverse events and serious adverse events

    Will be graded per Common Terminology Criteria for Adverse Events. Will evaluate any clinically meaningful trends in safety parameters.

    Measured: Up to 24 months

  6. Pharmacokinetic profile (Arm B)

    Will evaluate serum drug concentrations of ivonescimab in patients at different time points after ivonescimab administration.

    Measured: Before and end of infusion on cycle 1, day 1 and cycle 6, day 1; Before infusion on cycle 2, day 1, cycle 13, day 1, and at end of treatment (up to 24 months of treatment) 1 Cycle = 21 Days

  7. Number and percentage of patients with detectable anti-ivonescimab antibody (Arm B)

    Will evaluate serum drug concentrations of ivonescimab in patients at different time points after ivonescimab administration.

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2026
  2. Study start11 Jan 2027 (estimated)
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
336 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07765433
Sponsor's protocol ID
EA2251
Other IDs
NCI-2026-04569, EA2251, EA2251, U10CA180820
Status last verified
Aug 2026
First submitted
10 Aug 2026
Last updated
14 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Biospecimen Collection, Cisplatin and Computed Tomography in people with Locally Advanced Biliary Tract Adenocarcinoma and Locally Advanced Extrahepatic Cholangiocarcinoma, run by ECOG-ACRIN Cancer Research Group.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 45 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (OS) (time frame: From date of randomization until the date of death from any cause, assessed up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07765433.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2026.

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