a study to evaluate the efficacy and safety of pemigatinib versus chemotherapy in unresectable or metastatic cholangiocarcinoma

Conditions: Unresectable Cholangiocarcinoma; Metastatic Cholangiocarcinoma

Summary: 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.


Eligibility criteria:
inclusion criteria: * male and female participants at least 18 years of age at the time of signing the informed consent form (icf). * 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, or enrolled as of amendment 6 (or amendment 5-jp2) and the participant received 1 cycle of gemcitabine plus cisplatin \[the start of study drug {cycle 1 day 1} must be at least 14 days and ≤ 4 weeks {28 days} from the last dose of gemcitabine plus cisplatin\]). * 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.

Keywords: cholangiocarcinoma fibroblast growth factor receptor inhibitor fgfr fgfr rearrangement