Alternating Chemo-immunotherapy and FGFR Inhibitor for FGFR-positive Biliary or Cholangiocarcinoma

NCT07780838 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-25058NCI-2026-05653
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well giving gemcitabine, cisplatin and durvalumab alternating with pemigatinib for the treatment of biliary tract cancer with FGFR2 alterations that cannot be removed by surgery (unresectable), 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). Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill cancer cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pemigatinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals cancer cells to multiply. This may help keep cancer cells from growing and may kill them. Giving gemcitabine, cisplatin and durvalumab alternating with pemigatinib may work well for the treatment of unresectable, locally advanced or metastatic biliary tract cancer with FGFR2 alterations.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  Defined as the date of start of treatment to the date of death due to any cause. Will be analyzed using the Kaplan Meier method. Survival rate at 12 months and median OS will be estimated along with 95% confidence intervals from the Kaplan Meier distribution.

  At 12 months

Secondary Outcomes (15)

• Overall response rate (ORR)

  Up to 5 years

• Disease control rate

  Up to 5 years

• Duration of response

  Up to 5 years

• Duration of therapy (DOT)

  From start of cyclical therapy to termination of cyclical therapy, up to 5 years

• Progression free survival (PFS)

  From start of treatment to the event defined as the first documented progression or death due to any cause, up to 5 years

Study Arms (1)

Treatment (chemoimmunotherapy, FGFRi cycles)

EXPERIMENTAL

See Detailed Description

Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Biological: Durvalumab; Drug: Gemcitabine; Procedure: Magnetic Resonance Imaging; Drug: Pemigatinib; Other: Survey Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (chemoimmunotherapy, FGFRi cycles)

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

Treatment (chemoimmunotherapy, FGFRi cycles)

Computed Tomography PROCEDURE

Undergo CT scan

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

Treatment (chemoimmunotherapy, FGFRi cycles)

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

Treatment (chemoimmunotherapy, FGFRi cycles)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Treatment (chemoimmunotherapy, FGFRi cycles)

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

Treatment (chemoimmunotherapy, FGFRi cycles)

Pemigatinib DRUG

Given PO

Also known as: INCB 054828, INCB-054828, INCB054828, Pemazyre

Treatment (chemoimmunotherapy, FGFRi cycles)

Survey Administration OTHER

Ancillary studies

Treatment (chemoimmunotherapy, FGFRi cycles)

Eligibility Criteria

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

You may qualify if:

• Adults 18 years of age or older with histologically or cytologically confirmed unresectable locally advanced or metastatic carcinoma of the biliary tract, including intrahepatic and extrahepatic cholangiocarcinoma, gallbladder, and ampulla of Vater, at the time of diagnosis
• Patients must have tumors classified as having FGFR2 gene fusion/rearrangements or other gain-of function alterations involved in FGFR as detected by any analytically validated, Clinical Laboratory Improvement Act (CLIA)-certified molecular testing, including commercial tests (Foundation Medicine, Caris, Tempus, Guardant360, and others) or other platforms of next generation sequencing. Gene rearrangements are structural variants that can include inversions, translocations, duplications, and truncations. In addition, all patients will have tumor specimens sent and stored centrally
• One or more measurable lesions per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Patients with ECOG performance status of 2 may be considered on a case-by-case basis by Principal Investigator
• Life expectancy of greater than 4 months
• Ability to understand and participate voluntarily, sign informed consent, and follow the study treatment plan and scheduled visits
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/mm3)
• Note: Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection
• Platelets ≥ 75 × 109/L
• Note: Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection
• Hemoglobin ≥ 90 g/L (9 g/dL)
• Note: Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection
• Prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT) are all ≤ 1.5 × upper limits of normal (ULN), with the exception of patients taking blood thinners with coagulation factor elevation associated with these drugs
• Serum bilirubin ≤ 1.5 × ULN (≤ 5 × ULN if the tumor involves the liver), unless associated with patient's primary cancer and/or metastases and with Principal Investigator's approval; biliary drains and stents are acceptable
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are ≤ 3 × ULN (if with liver metastases, AST and ALT ≤ 5 × ULN), unless associated with patient's primary cancer and/or metastases and with Principal Investigator's approval; biliary drains and stents are acceptable

You may not qualify if:

• Patients who have not recovered from reversible toxicity of prior anti-tumor therapy (except toxicities which are not clinically significant such as alopecia, grade 0-2 neuropathy)
• Patients who received prior FGFR-targeted therapy
• Within 2 weeks before the first dose of study drug, the subject's calcium and phosphate level continuing to exceed the ULN despite medical treatment
• Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis, or medical conditions that increase their risk of developing hyperphosphatemia or hypercalcemia
• History and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, and lung, with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification
• Patients with clinically significant gastrointestinal dysfunction that may affect drug intake, transport or absorption (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
• Current evidence of corneal or retinal abnormalities that may increase eye toxicity, including but not limited to:
• Currently suffering from central serous retinopathy (CSR) or retinal vein occlusion (RVO), or with relevant history;
• Active wet age-related macular degeneration (wAMD);
• Diabetic retinopathy with macular edema;
• Uncontrollable glaucoma;
• Keratopathy, such as keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation or ulceration
• Consumed or anticipate consuming diet or drugs known to be strong or moderate cytochrome P450 (CYP) 3A4 inhibitors, strong CYP3A4 inducers or strong inhibitors of efflux transports including P-gp and BCRP for 28 days (or 5 half-lives, whichever is shorter) before the first dose of study drug or during the study drug treatment
• Patients with active or prior documented autoimmune or inflammatory disorders
• Participants must not have an active, known or suspected autoimmune disease which may affect vital organ function or has/may require systemic immunosuppressive therapy for management. Participants with inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]) are also excluded with the exception of the following: participants with type I diabetes mellitus, hypothyroidism (e.g. following Hashimoto syndrome) only requiring and stable on hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (such as celiac disease controlled by diet) are permitted to enroll. Patients without active disease for 5 years may also be enrolled after consultation with the study physician

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• Incyte Corporation: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Cholangiocarcinoma; Gallbladder Neoplasms

Interventions

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

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases

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

• Sameek Roychowdhury, MD, PhD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 7, 2026
• First Posted: August 24, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 10, 2026

Record last verified: 2026-09

Locations

US (1)