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.
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).
Diagnosis of another malignancy within 5 years before the first dose of study treatment, except for definitively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or carcinoma in situ that has been curatively resected.
Prior treatment with a selective FGFR inhibitor.
Failure to adequately recover from toxicities and/or complications resulting from any prior intervention before treatment initiation (i.e., recovery to Grade ≤ 1 or baseline), except for fatigue or alopecia.
Known symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may be eligible if they are clinically stable, have no radiographic evidence of progression for at least 4 weeks before the first dose of study treatment, have no evidence of new or enlarging brain metastases on repeat imaging, and have not required steroid treatment for at least 14 days before the first dose of study treatment. Patients with carcinomatous meningitis are excluded regardless of clinical stability.
Parallel
Pemigatinb
DrugPemigatinib will be administered orally once daily in a self-administered manner. Each treatment cycle will consist of 21 days, including 14 consecutive days of treatment followed by a 7-day treatment-free period. The dose will be 13.5 mg once daily.
PD-1 inhibitors
DrugPD-1 inhibitors are not restricted to a specific agent. Commonly used agents include pembrolizumab and toripalimab. PD-1 inhibitors will be administered by intravenous infusion on Day 1 of each 21-day cycle (Q3W). The recommended doses are 200 mg for pembrolizumab and 240 mg for toripalimab. The dosage and administration of other PD-1 inhibitors will be based on the respective product labeling.
Chemotherapy
DrugThe decision to administer combination chemotherapy will be made by the investigator based on a comprehensive assessment of the patient's performance status, organ function, and personal preferences. Combination chemotherapy is generally recommended as part of the standard treatment regimen; however, it may be omitted in patients who are unable to tolerate chemotherapy due to poor general condition or impaired organ function. If combination chemotherapy is administered, the chemotherapeutic agents will be given by intravenous infusion on Day 1 of each 21-day treatment cycle, with one cycle consisting of 3 weeks (Q3W). The most commonly used chemotherapy regimen is the GEMOX regimen.
PFS, progression free survival
Progression-Free Survival was defined as the time from treatment initiation to the first occurrence of disease progression or death from any cause.
Objective response rate (ORR)
Proportion of participants with a best overall response of complete response or partial response according to RECIST version 1.1, as assessed by investigators. Tumor assessments were performed at baseline, every two treatment cycles during induction (each treatment cycle was 21 days), and approximately every 6-9 weeks during maintenance.
Disease control rate
Proportion of participants with a best overall response of complete response, partial response, or stable disease according to RECIST version 1.1, as assessed by investigators. Tumor assessments were performed at baseline, every two treatment cycles during induction (each treatment cycle was 21 days), and approximately every 6-9 weeks during maintenance.
Overall Survival (OS)
Overall survival was defined as the time from the first dose of study treatment to death from any cause.
Safety and Tolerability
The incidence, type, and severity of adverse events, treatment-related adverse events, serious adverse events, and clinically significant abnormalities in laboratory test results and vital signs. Adverse events were graded according to NCI CTCAE version 5.0.
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Haitao Zhao, MD
Lead sponsor
Peking Union Medical College Hospital
Sponsor institution