AB801 in Combination With Chemotherapy and Immunotherapy for the Treatment of Patients With Borderline Resectable, Locally Advanced or Metastatic Cholangiocarcinoma or Pancreatic Cancer

NCT07619313 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 25-2512NCI-2026-03183
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, best dose and effectiveness of AB801 in combination with chemotherapy and immunotherapy in treating patients with cholangiocarcinoma or pancreatic adenocarcinoma that may be removed by surgery (borderline resectable), that has spread to nearby tissue or lymph nodes (locally advanced), or that has spread from where it first started (primary site) to other places in the body (metastatic). AB801 is a drug designed to block a protein called AXL. AXL is found on the surface of certain cancer cells and plays an important role in helping tumors grow, spread to other parts of the body, and avoid the immune system. It is thought to contribute to resistance against common cancer treatments such as chemotherapy, radiation and immunotherapy. In many cancers, including cholangiocarcinoma and pancreatic adenocarcinoma, AXL is overactive and associated with worse outcomes. AB801 inhibits AXL which may make cancer cells more sensitive to chemotherapy and allow immune cells to better recognize and attack the tumor. Chemotherapy drugs, such as gemcitabine, cisplatin, oxaliplatin, irinotecan, leucovrin and fluorouracil, work in different ways to stop the growth of cancer cells either by killing the cells, by stopping them from dividing or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as durvalumab and zimberelimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving AB801 in combination with chemotherapy and immunotherapy may better treat patients with borderline resectable, locally advanced or metastatic cholangiocarcinoma or pancreatic adenocarcinoma.

Conditions

Metastatic Pancreatic Adenocarcinoma; Stage IV Pancreatic Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage II Pancreatic Cancer AJCC v8; Borderline Resectable Pancreatic Ductal Adenocarcinoma; Locally Advanced Cholangiocarcinoma; Locally Advanced Pancreatic Adenocarcinoma; Metastatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of dose limiting toxicities

  Overall exposure to study drug, the numbers of participants completing each cycle, and the dose intensity will be summarized using descriptive statistics. The number of participants with any dose adjustment will be presented for entire treatment period as well as for each cycle. The number of participants with dose reductions, dose delays, or dose omissions will also be summarized, as will the reasons for dose adjustments. Adverse events and serious adverse events will be reported using Common Terminology Criteria for Adverse Events version 5 terminology and severity.

  During first cycle of the dose escalation phase (cycle length = 21 days for cohort I and 28 days for cohort II)

Secondary Outcomes (5)

• Overall response rate (ORR)

  Up to 2 years

• Duration of response

  up to 2 years

• Progression-free survival

  up to 2 years

• Overall survival

  Up to 2 years

• Proportion of patients take to curative surgery

  Up to 2 years

Study Arms (2)

Cohort I (AB801, gemcitabine, cisplatin, durvalumab)

EXPERIMENTAL

Patients with cholangiocarcinoma receive AB801 PO QD, gemcitabine and cisplatin IV over 30 minutes on days 1 and 8 and durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI throughout the trial as well as tissue biopsy on trial.

Procedure: Biopsy Procedure; Drug: Cisplatin; Procedure: Computed Tomography; Biological: Durvalumab; Drug: Gemcitabine; Drug: Ligritinib; Procedure: Magnetic Resonance Imaging

Cohort II (AB801, zimberelimab, FOLFIRINOX)

EXPERIMENTAL

Patients with pancreatic cancer receive AB801 PO QD and zimberelimab IV over 60 minutes on day 1 of each cycle. Patients receive oxaliplatin IV over 120 minutes, leucovorin IV, and irinotecan IV on days 1 and 15 of each cycle and fluorouracil IV over 46 hours on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI throughout the trial as well as tissue biopsy on trial.

Procedure: Biopsy Procedure; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Irinotecan; Drug: Leucovorin; Drug: Ligritinib; Procedure: Magnetic Resonance Imaging; Drug: Oxaliplatin; Drug: Zimberelimab

Interventions

Biopsy Procedure PROCEDURE

Undergo tissue biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Cohort I (AB801, gemcitabine, cisplatin, durvalumab); Cohort II (AB801, zimberelimab, FOLFIRINOX)

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

Cohort I (AB801, gemcitabine, cisplatin, durvalumab)

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

Cohort I (AB801, gemcitabine, cisplatin, durvalumab); Cohort II (AB801, zimberelimab, FOLFIRINOX)

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

Cohort I (AB801, gemcitabine, cisplatin, durvalumab)

Fluorouracil DRUG

Given IV

Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Cohort II (AB801, zimberelimab, FOLFIRINOX)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Cohort I (AB801, gemcitabine, cisplatin, durvalumab)

Irinotecan DRUG

Given IV

Cohort II (AB801, zimberelimab, FOLFIRINOX)

Leucovorin DRUG

Given IV

Also known as: Folinic acid

Cohort II (AB801, zimberelimab, FOLFIRINOX)

Ligritinib DRUG

Given PO

Also known as: AB 801, AB-801, AB801, AXL Inhibitor AB801

Cohort I (AB801, gemcitabine, cisplatin, durvalumab); Cohort II (AB801, zimberelimab, FOLFIRINOX)

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

Cohort I (AB801, gemcitabine, cisplatin, durvalumab); Cohort II (AB801, zimberelimab, FOLFIRINOX)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, Elplat, JM 83, JM-83, JM83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, RP54780, SR 96669, SR-96669, SR96669

Cohort II (AB801, zimberelimab, FOLFIRINOX)

Zimberelimab DRUG

Give IV

Also known as: AB 122, AB-122, AB122, Anti-PD-1 Monoclonal Antibody GLS-010, GLS 010, GLS-010, GLS010, Sepalizumab, WBP 3055, WBP-3055, WBP3055

Cohort II (AB801, zimberelimab, FOLFIRINOX)

Eligibility Criteria

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

You may qualify if:

• Male or female ≥ 18 years of age and willing and able to provide informed consent
• Previously untreated cytologically or histologically confirmed, at least one measurable lesion via Response Evaluation Criteria in Solid Tumors (RECIST 1.1) of cholangiocarcinoma or pancreatic adenocarcinoma meeting following criteria:
• Cholangiocarcinoma
• Borderline resectable/locally advanced cholangiocarcinoma: to be defined as unresectable disease on evaluation by a hepatobiliary multi-disciplinary tumor board/surgeon based on tumor size/location, vascular involvement, and absence of extrahepatic metastasis.
• Metastatic cholangiocarcinoma: Patients with metastatic cholangiocarcinoma patient who have not received prior systemic therapy
• Pancreatic adenocarcinoma
• Borderline resectable pancreatic adenocarcinoma: There are multiple definitions of borderline resectable pancreatic ductal adenocarcinoma (PDAC). For the purposes of this study, borderline resectable disease will be identified per the National Comprehensive Cancer Network (NCCN) criteria. Per this definition, borderline resectable PDAC is defined as the presence of any one or more of the following on CT:
• An interface between the tumor and superior mesenteric artery (SMA) or celiac axis (CA) measuring \< 180º of the circumference of the vessel wall.
• An interface between the tumor with the common hepatic artery without extension into the celiac axis or hepatic artery bifurcation allowing for safe and complete resection and reconstruction.
• An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring ≥ 180° of the circumference of the vessel wall
• Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction
• An interface between the primary tumor and the inferior vena cava (IVC)
• Locally advanced pancreatic adenocarcinoma: Multiple guidelines defining locally advanced PDAC have been developed. For the purposes of this study, locally advanced PDAC cases will be identified per the definition developed by the NCCN. Per this definition, locally advanced PDAC is defined as presence of any one or more of the following on CT:
• Interface between the tumor and SMA or CV measuring \> 180º of the circumference of the vessel wall or solid tumor contact with the CA and aortic involvement.
• Occlusion of the SMV-PV that is not amenable to resection and venous reconstruction

You may not qualify if:

• Previous treatment with any of planned study drugs in cholangiocarcinoma, though patients with one cycle of gemcitabine/cisplatin/durvalumab will be considered eligible
• Previous treatment with any of planned study drugs in pancreatic adenocarcinoma, though patients with one cycle of FOLFIRINOX will be considered eligible
• Peripheral neuropathy \> grade 2
• Known status of HIV which is not well-controlled (CD4 \< 300) at the time of study eligibility. Patients with controlled and treated HIV/hepatitis C virus (HCV) and an undetectable viral load are allowed
• Untreated hepatitis B infection; Patient has known active hepatitis B virus (HBV) or hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection (testing is not mandatory, unless known active or known history of infection or required by local regulation):
• Participants with resolved or treated HCV (ie, HCV antibody positive but undetectable HCV ribonucleic acid \[RNA\]) will not be excluded from this study
• Underlying medical conditions that, in the Investigator's opinion, will make the administration of investigational product (IP)(s) hazardous, including but not limited to:
• Interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis
• Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of the IP,
• Active infection or antibiotics within 48 hours prior to study screening;
• A condition or unresolved adverse event (AE) from a prior investigational drug that may obscure the interpretation of toxicity determination or AEs,
• History of prior solid-organ transplantation
• Any history of malignancy less than 5 years prior to the time of study eligibility (Patients with history of skin cancers excluding melanoma and cancers with a very low risk of recurrence i.e., low grade prostate cancer, thyroid cancer and low risk cervical cancer will be eligible for participation)
• Serious medical comorbidities such as New York Heart Association Class III/IV cardiac disease, uncontrolled cardiac arrhythmias, myocardial infarction over the past 12 months
• Known family history or personal history of long QTc syndrome or previous drug-induced QTc prolongation of at least grade 3 (QTc \> 500 ms)

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Pancreatic Neoplasms

Interventions

Biopsy; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; durvalumab; Immunoglobulin G; Disulfides; Fluorouracil; dehydroftorafur; Gemcitabine; Irinotecan; Leucovorin; Magnetic Resonance Spectroscopy; Oxaliplatin; zimberelimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; 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; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Spectrum Analysis; Chemistry Techniques, Analytical; Coordination Complexes

Study Officials

• Lee S Rosen

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2026
• First Posted: June 2, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 4, 2026

Record last verified: 2026-05

Locations

US (1)