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

NCT07765433 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: EA2251NCI-2026-04569U10CA180820
• Study Type: interventional
• Target: 336
• Locations: 0 countries
• Sites: N/A

Brief 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 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.

Conditions

Locally Advanced Biliary Tract Adenocarcinoma; Locally Advanced Extrahepatic Cholangiocarcinoma; Locally Advanced Intrahepatic Cholangiocarcinoma; Locally Advanced Unresectable Gallbladder Adenocarcinoma; Metastatic Biliary Tract Adenocarcinoma; Metastatic Extrahepatic Cholangiocarcinoma; Metastatic Gallbladder Adenocarcinoma; Metastatic Intrahepatic Cholangiocarcinoma; Stage III Distal Bile Duct Cancer AJCC v8; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Distal Bile Duct Cancer AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8; Unresectable Biliary Tract Adenocarcinoma; Unresectable Extrahepatic Cholangiocarcinoma; Unresectable Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

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

Secondary Outcomes (7)

• Progression-free survival

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

• Objective response rate

  Up to 3 years

• Duration of response

  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

• Disease control rate

  From 9 weeks from date of randomization up to 3 years

• Incidence and severity of adverse events and serious adverse events

  Up to 24 months

Other Outcomes (3)

• Estimates of the primary OS outcome treatment effect by sex

  Up to 3 years

• Estimates of the primary OS outcome treatment effect by race

  Up to 3 years

• Estimates of the primary OS outcome treatment effect by ethnicity

  Up to 3 years

Study Arms (2)

Arm A (gemcitabine, cisplatin, durvalumab, pembrolizumab)

ACTIVE COMPARATOR

Patients 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.

Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Biological: Durvalumab; Drug: Gemcitabine Hydrochloride; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab

Arm B (gemcitabine, cisplatin, ivonescimab)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Gemcitabine Hydrochloride; Biological: Ivonescimab; Procedure: Magnetic Resonance Imaging

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm A (gemcitabine, cisplatin, durvalumab, pembrolizumab); Arm B (gemcitabine, cisplatin, ivonescimab)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm A (gemcitabine, cisplatin, durvalumab, pembrolizumab); Arm B (gemcitabine, cisplatin, ivonescimab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm A (gemcitabine, cisplatin, durvalumab, pembrolizumab); Arm B (gemcitabine, cisplatin, ivonescimab)

Durvalumab BIOLOGICAL

Given IV

Also known as: 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, MEDI4736

Arm A (gemcitabine, cisplatin, durvalumab, pembrolizumab)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar, LY 188011, LY-188011, LY188011

Arm A (gemcitabine, cisplatin, durvalumab, pembrolizumab); Arm B (gemcitabine, cisplatin, ivonescimab)

Ivonescimab BIOLOGICAL

Given IV

Also known as: AK 112, AK-112, AK112, Anti-PD-1/Anti-VEGF Bispecific Antibody AK112, Anti-PD-1/VEGF Bispecific Antibody AK112, PD-1/VEGF Bispecific Antibody AK112, SMT 112, SMT-112, SMT112

Arm B (gemcitabine, cisplatin, ivonescimab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm A (gemcitabine, cisplatin, durvalumab, pembrolizumab); Arm B (gemcitabine, cisplatin, ivonescimab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475

Arm A (gemcitabine, cisplatin, durvalumab, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

Sponsors & Collaborators

• ECOG-ACRIN Cancer Research Group: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Specimen Handling; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; durvalumab; Immunoglobulin G; Disulfides; Gemcitabine; Magnetic Resonance Spectroscopy; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Deirdre J Cohen

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 10, 2026
• First Posted: August 14, 2026
• Study Start (Estimated): January 11, 2027
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: August 14, 2026

Record last verified: 2026-08