Purpose

The purpose of this study is to evaluate the efficacy and safety of pemigatinib versus gemcitabine plus cisplatin chemotherapy in first-line treatment of participants with unresectable or metastatic cholangiocarcinoma with FGFR2 rearrangement.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Male and female participants at least 18 years of age at the time of signing the informed consent form (ICF); a legally minor participant from Japan needs written parental consent.
  • Histologically or cytologically confirmed cholangiocarcinoma that is previously untreated and considered unresectable and/or metastatic (Stage IV per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual).
  • Radiographically measurable or evaluable disease by CT or MRI per RECIST v1.1 criteria.
  • Eastern Cooperative Oncology Group performance status 0 to 1.
  • Documented FGFR2 rearrangement.
  • Willingness to avoid pregnancy or fathering children.

Exclusion Criteria

  • Received prior anticancer systemic therapy for unresectable and/or metastatic disease (not including adjuvant/neo-adjuvant treatment completed at least 6 months prior to enrollment, and participants that have received treatment for locally advanced disease with trans-arterial chemoembolization or selective internal radiation therapy, if clear evidence of radiological progression is observed before enrollment).
  • Child-Pugh B and C.
  • Toxicities related to prior therapy(ies) must be Common Terminology Criteria for Adverse Events (CTCAE) v5.0 ≤ Grade 1 at the time of screening.
  • Concurrent anticancer therapy, other than the therapies being tested in this study.
  • Participant is a candidate for potentially curative surgery.
  • 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 central serous retinopathy, macular/retinal degeneration, diabetic retinopathy, retinal detachment) as confirmed by ophthalmologic examination.
  • Radiation therapy administered within 4 weeks of enrollment/randomization/first dose of study treatment.
  • Known central nervous system (CNS) metastases or history of uncontrolled seizures.
  • Known additional malignancy that is progressing or requires active treatment (exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
  • Laboratory values at screening outside the protocol-defined range.
  • History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues, such as the skin, kidney, tendons or vessels due to injury, disease, and aging, in the absence of systemic mineral imbalance).
  • Significant gastrointestinal disorders that could interfere with absorption, metabolism, or excretion of pemigatinib.
  • Clinically significant or uncontrolled cardiac disease.
  • History or presence of an abnormal ECG, which, in the investigator's opinion, is clinically meaningful.
  • Chronic or current active infectious disease requiring systemic antibiotics or antifungal or antiviral treatment within 2 weeks prior to enrollment (participants with asymptomatic chronic infections on prophylactic treatment are allowed). Note: HIV-positive participants are allowed if all of the following criteria are met: CD4+ count ≥ 300/µL, undetectable viral load, receiving antiretroviral therapy that does not interact with study drug, and no HIV/AIDS-associated opportunistic infection in the last 12 months.
  • 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 treatment. Note: Moderate CYP3A4 inhibitors are not prohibited
  • Known hypersensitivity or severe reaction to pemigatinib, gemcitabine, cisplatin, or their excipients.
  • Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Pemigatinib
  • Drug: Pemigatinib
    Pemigatinib at the protocol-defined dose administered orally once daily as continuous therapy schedule (a cycle is 3 weeks).
    Other names:
    • INCB054828
Active Comparator
Gemcitabine + Cisplatin
Participants who experience disease progression while receiving gemcitabine + cisplatin or during the follow-up period and before starting a new anticancer therapy will be eligible to cross over and receive pemigatinib.
  • Drug: Gemcitabine
    Gemcitabine 1000 mg/m^2 administered as an intravenous infusion on Days 1 and 8 of every 3-week cycle for up to 8 cycles.
  • Drug: Cisplatin
    Cisplatin 25 mg/m^2 administered as an intravenous infusion on Days 1 and 8 of every 3-week cycle for up to 8 cycles.

Recruiting Locations

Boston Medical Center
Boston, Massachusetts 02118
Contact:
Study Coordinator
617-638-8213

More Details

Status
Recruiting
Sponsor
Incyte Corporation

Study Contact

Incyte Corporation Call Center (US)
1.855.463.3463
medinfo@incyte.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.