A Phase II Study of Pemigatinib Plus Durvalumab in Previously Treated Advanced Intrahepatic Cholangiocarcinoma Patients With FGFR-2 Fusion or Rearrangement

Recruiting now · Phase 2

Conditions studied: Intrahepatic Cholangiocarcinoma, FGFR2 Gene Rearrangement, FGFR2 Gene Mutation

In brief

This is a single arm phase II study of pemigatinib and durvalumab combination in patients with FGFR-2 fusion or rearrangement positive intrahepatic cholangiocarcinoma. Each cycle will be 3 weeks. Pemigatinib is administered at 13.5 mg orally daily 2 weeks on and 1 week off. Durvalumab is administered at 1500 mg intravenously once every 3 weeks. Subjects will require a visit with appropriate laboratory work prior to the start of each cycle. Disease assessment will occur every 9 weeks. Subjects will continue treatment until progression per RECIST 1.1, toxicity or subject/physician decision. A maximum of 24 months (about 35 cycles) of pemigatinib and durvalumab treatment from Cycle 1 Day 1 is allowed.

Key facts

Study ID

NCT06728410

Run by

Mehmet Akce

People needed

38

Starts

2026-01-27

Expected to finish

2027-07-01

Last updated by the study team

2026-05-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0 or 1.
• Body weight of > 30 kg.
• Histologically diagnosed locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma with FGFR-2 fusion or rearrangement detected by Clinical Laboratory Improvement Act (CLIA)-certified assays including commercial tests (Foundation Medicine, Caris, Tempus, Guardant 360 or other platforms of next generation sequencing will be allowed). AJCC, 8th edition. Subjects with gallbladder cancer or ampulla of Vater carcinoma are not eligible.
• Measurable disease according to RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have received gemcitabine cisplatin and durvalumab or another anti-PD-1 Ab for unresectable locally advanced or metastatic cholangiocarcinoma with either disease progression, intolerance to cytotoxic chemotherapy, or have received at least 6 months of therapy with stable disease or partial response. Prior neoadjuvant or adjuvant therapy is permitted if documented disease recurrence occurred ≥ 6 months after the last date of neoadjuvant or adjuvant therapy.
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration.
• Absolute Neutrophil Count (ANC): ≥1500/µL
• Hemoglobin (Hgb): ≥ 9 g/dL; Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
• Platelet (PLT): ≥ 100 000/µL
• Calculated creatinine clearance: >40 mL/min
• Bilirubin: ≤ 1.5 × upper limit of normal (ULN) This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with the sponsor-investigator.
• Aspartate aminotransferase (AST): ≤ 2.5 × institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
• Alanine aminotransferase (ALT): ≤ 2.5 × institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
• International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT): ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
• Females of childbearing potential must have a negative serum pregnancy test at screening.
• Females of childbearing potential who are sexually active with a male able to father a child must be willing to use an effective method(s) of contraception. Males able to father a child who are sexually active with female of childbearing potential must be willing to use an effective method(s) of contraception.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Must have a life expectancy of at least 12 weeks.

You may not qualify if…

• Prior therapy with a FGFR inhibitor.
• Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to macular/retinal degeneration, diabetic retinopathy, and retinal detachment) as confirmed by ophthalmologic examination
• History of calcium and phosphate homeostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues such as the skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance)
• Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug. Moderate CYP3A4 inhibitors are not prohibited but should be avoided.
• History of hypovitaminosis D requiring supraphysiologic doses (eg, 50,000 UI/weekly) to replenish the deficiency. Vitamin D supplements are allowed.
• Participation in another clinical study with an investigational product during the last 3 months
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤ 28 days prior to the first dose of study regimen. If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by sponsor-investigator.
• Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
• Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the sponsor-investigator.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with the study regimen may be included only after consultation with the sponsor-investigator.
• Any concurrent chemotherapy, study drug, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study regimen.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study regimen. NOTE: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or 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]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the sponsor-investigator
• Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of the study regimen and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

Where it is running

• University of Alabama at Birmingham — Birmingham, Alabama, United States (enrolling)
• Roswell Park Cancer Institute — Buffalo, New York, United States (enrolling)

Full record on ClinicalTrials.gov

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