Pemigatinib Plus PD-1 Inhibitor With or Without Chemotherapy in FGFR2 Fusion/Rearrangement-Positive Cholangiocarcinoma

NCT07786766 | Recruiting Phase 2

• 1 other identifier: K9903
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Biliary Tract Cancer (BTC)

Keywords

Biliary Tract Cancer; Immune Checkpoint Inhibitors; Pemigatinib

Outcome Measures

Primary Outcomes (1)

• 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.

  From date of randomization until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 24 months.

Secondary Outcomes (5)

• Objective response rate (ORR)

  From date of randomization until the date of last tumor assessment, with tumor response evaluated every 6-9 weeks up to 24 months; objective response is defined as confirmed CR or PR per RECIST v1.1 criteria.

• Disease control rate

  From date of randomization until the date of last tumor assessment, with disease status evaluated every 6-9 weeks up to 24 months; disease control is defined as confirmed CR, PR, or stable disease (SD) per RECIST v1.1 criteria.

• Overall Survival (OS)

  From date of randomization until the date of death from any cause or the date of last valid follow-up, whichever came first, assessed up to 24 months.

• Safety and Tolerability

  From the date of first study drug administration until 30 days after the date of last study drug administration, with all adverse events monitored and documented continuously throughout the treatment period and post-treatment follow-up.

• DoR, duration of response

  From the date of first confirmed complete response (CR) or partial response (PR) until the date of disease progression or death from any cause, whichever came first, assessed up to 24 months.

Study Arms (2)

First-line

EXPERIMENTAL

Drug: Pemigatinb; Drug: PD-1 inhibitors; Drug: Chemotherapy

Second-line

EXPERIMENTAL

Drug: Pemigatinb; Drug: PD-1 inhibitors; Drug: Chemotherapy

Interventions

Pemigatinb DRUG

Pemigatinib 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.

First-line; Second-line

PD-1 inhibitors DRUG

PD-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.

First-line; Second-line

Chemotherapy DRUG

The 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.

First-line; Second-line

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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).
• \. 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.
• \. 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).

You may not qualify if:

• 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.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Any of the following laboratory abnormalities:
• )Serum phosphate level \> ULN. 2)Serum calcium outside the normal range, or albumin-corrected serum calcium outside the normal range if serum albumin is outside the normal range.
• )Potassium level below the lower limit of normal. Potassium supplementation is permitted to correct the potassium level during screening.
• \. Known history of human immunodeficiency virus (HIV) infection or a confirmed positive HIV test result.
• \. Active or clinically uncontrolled serious infection. 9. Clinically significant pleural effusion, ascites, or pericardial effusion requiring drainage.
• \. Acute or chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, defined as HBV DNA \> 2,000 IU/mL or \> 10⁴ copies/mL, HCV RNA \> 10³ copies/mL, or concurrent positivity for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies. Patients whose viral load decreases below these thresholds after nucleos(t)ide analogue antiviral therapy may be eligible.
• \. Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months before the first dose of study treatment, New York Heart Association (NYHA) Class III or IV congestive heart failure, or uncontrolled arrhythmia. Patients with a pacemaker or atrial fibrillation with well-controlled heart rate may be eligible. Patients with clinically significant electrocardiogram (ECG) abnormalities or relevant cardiac history, as determined by the investigator, are also excluded.
• \. Uncontrolled hypertension despite optimal medical treatment, defined as systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg, or a history of hypertensive crisis or hypertensive encephalopathy.
• \. Hepatic encephalopathy, hepatorenal syndrome, Child-Pugh liver function score \> 7, or more severe cirrhosis.
• \. Major surgery, including craniotomy, thoracotomy, or laparotomy, within 4 weeks before the first dose of study treatment, or anticipated need for major surgery during the study treatment period.

Sponsors & Collaborators

• Haitao Zhao, MD: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, 100730, China

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Immune Checkpoint Inhibitors; Drug Therapy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Therapeutics

Central Study Contacts

Shi Feng

CONTACT

+86-10-69156042; fengshi0726@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director, Hepatobiliary Surgery, Peking Union Medical College Hospital

Study Record Dates

• First Submitted: August 21, 2026
• First Posted: August 26, 2026
• Study Start: August 20, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 26, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)