Pemigatinib in the Advanced Gastrointestinal Cancer With FGFR 1-3 Alterations

This study is a prospective single-arm phase II study to evaluate the efficacy and safety of Pemigatinib in the advanced gastrointestinal cancer with FGFR 1-3 alterations and failed standard therapy.

Inclusion Criteria:Aged 18 or olderHistologically or cytologically confirmed unresectable advanced, recurrent or metastatic gastrointestinal cancerHave at least one measurable lesion according to RECIST v1.1With histologically confirmed FGFR1-3 alterations, including but not limited to amplification, mutation, fusion/rearrangementDisease progression after prior standard therapyNo previous use of small molecule multi-target inhibitors targeting the FGFR pathway (including but not limited to anlotinib, lenvatinib, sorafenib, apatinib)ECOG performance status of 0~1Expected survival time > 3 monthsSufficient organ functionsNegative pregnancy test results of childbearing age womenPatients at risk of conception (including their partners) need to use contraceptionExclusion Criteria:Diagnosed with malignant tumors other than gastrointestinal cancer within 5 years before the first dose, excluding radically cured cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, and/or radically resected carcinoma in situPrior receipt of selective FGFR inhibitorsHave received any other investigational drug or participated in another interventional clinical trial within 28 days before the first dose, or have received anti-tumor drug treatment within 28 days before the first dose (including Chinese herbal medicine with anti-tumor indications)Have not recovered ( ≤ grade 1 or reaching the baseline, excluding asthenia and alopecia) from toxicity and/or complications caused by any intervention before the start of treatmentKnown symptomatic central nervous system metastasis and/or carcinomatous meningitis.Known history of allotransplantation or allogeneic hematopoietic stem cell transplantationAbnormal laboratory parameters listed below:Serum phosphate > upper limit of normal (ULN)Serum calcium exceeds the normal range, or the calcium concentration corrected for serum albumin exceeds the normal range when serum albumin exceeds the normal rangePotassium level < lower limit of normal (LLN)#potassium levels can be corrected by supplements at screeningKnown history of human immunodeficiency virus (HIV) infection or confirmed with positive immune test resultsPresence of severe infection in the active phase or with poor clinical controlPleural effusion, ascites, or pericardial effusion with obvious clinical symptoms that require drainageAcute or chronic active hepatitis B or C infectionClinically significant or uncontrolled heart diseases, including unstable angina, acute myocardial infarction within 6 months before the first dose, grade III/IV congestive heart failure (New York Heart Association), and uncontrolled arrhythmia (patients with pacemakers or with atrial fibrillation but well controlled heart rate are allowed)ECG changes or medical history considered clinically significant by the investigator, QTcF interval > 480 ms at screening, JTc interval can be used instead of QTc interval (in such cases, JTc must be ≤ 340 ms) for patients with intraventricular conduction block (QRS interval > 120 ms)Uncontrolled hypertension (systolic pressure > 160 mmHg or diastolic pressure > 100 mmHg) after the optimal medical treatment, or a history of hypertensive crisis or hypertensive encephalopathyHepatic encephalopathy, hepatorenal syndrome, or liver cirrhosis with Child-Pugh grade B or CHave received a major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose, or will receive a major surgery during the study treatment periodNot fully recovered from toxicity and/or complications of a major surgery before the study treatmentPregnant or lactating women, or patients expected to conceive or give birth during the study period from the screening to the completion of the safety follow-up visit (90 days after the last dose for male subjects)Have received radiotherapy within 4 weeks before the first dose.History of disorders of calcium and phosphorus metabolism or systemic electrolyte metabolism imbalance with ectopic calcification of soft tissues (excluding calcification of soft tissues such as skin, kidneys, tendon, or blood vessels without systemic electrolyte metabolism imbalance caused by injury, disease, and old age)Clinically significant corneal or retinal diseases confirmed by ophthalmological examinationPrior receipt of any potent CYP3A4 inhibitor or inducer within 14 days or 5 half lives (whichever is shorter) before the first dose. Ketoconazole is allowed for external useKnown allergic reactions to pemigatinib or excipients of pemigatinibUnable or unwilling to swallow pemigatinib or are suffering from significant digestive system diseases that may interfere with absorption, metabolism, or excretion