An Open-Label, Phase II Clinical Study Evaluating the Efficacy and Safety of Pemigatinib in Combination With a PD-1 Inhibitor, With or Without Chemotherapy, in Patients With Unresectable or Metastatic Cholangiocarcinoma Harboring FGFR2 Fusions or Rearrangements
This is a prospective, single-arm, phase II clinical study. Patients with advanced cholangiocarcinoma harboring FGFR2 fusions or rearrangements who have either not previously received standard therapy or have experienced treatment failure following standard therapy will be screened for eligibility and enrolled in the study after providing written informed consent.
‣ 1\. Male or female patients aged 18 to 80 years. 2. Histologically or cytologically confirmed unresectable locally advanced or metastatic biliary tract cancer (Stage III or IV according to the AJCC Cancer Staging Manual, 2010).
‣ 3\. At least one measurable lesion according to RECIST version 1.1. 4. Histologically confirmed FGFR2 fusion or rearrangement. 5. No prior treatment with a selective FGFR inhibitor, including pemigatinib, futibatinib, or other selective FGFR inhibitors.
‣ 6\. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 7. Estimated life expectancy of at least 6 months. 8. Adequate organ function, defined by the following laboratory criteria:
⁃ Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, without granulocyte colony-stimulating factor support within 14 days before assessment.
⁃ Platelet count ≥ 90 × 10⁹/L, without transfusion within 14 days before assessment.
⁃ Hemoglobin \> 9 g/dL, without transfusion or erythropoiesis-stimulating agent use within 14 days before assessment.
⁃ Total bilirubin ≤ 2.5 × the upper limit of normal (ULN).
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN; for patients with liver metastases, AST or ALT ≤ 5.0 × ULN is permitted.
⁃ Serum creatinine ≤ 1.5 × ULN and creatinine clearance, calculated using the Cockcroft-Gault formula, ≥ 50 mL/min.
⁃ Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN. Patients receiving anticoagulant therapy are eligible if their PT is within the intended therapeutic range of the anticoagulant.
• Women of childbearing potential must have a negative urine or serum pregnancy test within 3 days before the first administration of study treatment (Cycle 1, Day 1). A serum pregnancy test is required if a negative urine pregnancy test cannot be confirmed. Women not of childbearing potential are defined as those who have been postmenopausal for at least 1 year or have undergone surgical sterilization or hysterectomy.
⁃ All participants with reproductive potential, regardless of sex, must agree to use highly effective contraception, with a failure rate of less than 1% per year, throughout the treatment period and for 120 days after the last dose of study treatment (or 180 days after the last dose of chemotherapy, if applicable).