Phase I/II Trial of Pemigatinib in Combination With Atezolizumab and Bevacizumab for Treatment of Advanced Cholangiocarcinoma With FGFR2 Fusion

Recruiting now · Phase 1/Phase 2

Conditions studied: Advanced Cholangiocarcinoma, FGFR2 Fusion

In brief

To learn if pemigatinib in combination with atezolizumab and bevacizumab can help to control cholangiocarcinoma.

Key facts

Study ID

NCT06439485

Run by

M.D. Anderson Cancer Center

People needed

25

Starts

2024-11-19

Expected to finish

2030-02-22

Last updated by the study team

2026-07-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Ability to understand and willingness to sign informed consent.
• Age ≥18 years.
• Has histologically confirmed metastatic or advanced unresectable cholangiocarcinoma.
• Has disease that is measurable per the RECIST v1.1.
• Has at least one measurable target lesion.
• Has FGFR2 fusion or rearrangement in tumor tissue, as determined by CLIA-validated genomic testing of a tumor tissue specimen (DNA-based or RNA-based).
• Is refractory to, has demonstrated intolerance to, had received, or has refused access to, the 1st line systemic therapy including gemcitabine-based therapy with or without immunotherapy including durvalumab or pembrolizumab. Participants who discontinued available standard therapy due to toxicity must have continued evidence of measurable disease.
• Has available a formalin-fixed, paraffin-embedded primary tumor sample.
• Is able to take oral medication and to comply with protocol procedures and scheduled visits..
• Has Eastern Cooperative Oncology Group performance status of 0 or 1
• Has adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1000/µL) without granulocyte colony-stimulating factor support
• Platelet count ≥ 100 × 109/L (100,000/µL) without transfusion
• Hemoglobin ≥ 90 g/L (9 g/dL), participants may be transfused to meet this criterion.
• Aspartate amino transferate (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × upper limit of normal (ULN), with the following exceptions:
• Participants with documented liver metastases: AST and ALT ≤ 5 × ULN
• Participants with documented liver or bone metastases: ALP ≤ 5 × ULN
• Serum bilirubin ≤ 1.5 × ULN with the following exception:
• Participants with known Gilbert disease: serum bilirubin ≤ 3 × ULN
• Serum creatinine ≤ 1.5 × ULN
• Serum albumin ≥ 25 g/L (2.5 g/dL)
• For participants not receiving therapeutic anticoagulation: international normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. For patients on anticoagulation, those on therapeutic anticoagulation over 2 weeks are eligible.
• Has a negative human immunodeficiency virus (HIV) test at screening with the following exception: participants with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200 and have an undetectable viral load.
• Has a negative hepatitis B surface antigen (HBsAg) test at screening (unless participant has chronic HBV on anti-viral therapy)
• Has a negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening (unless patient has chronic HBV on anti-viral therapy)

You may not qualify if…

• Received prior chemotherapy, biologic therapy, immunotherapy, or investigational agent within 3 weeks prior to initiation of study medications.
• Had previous treatment with selective FGFR inhibitors including erdafitinib, infigratinib, or futibatinib.
• Had prior therapy with any VEGFR-targeting agent targeting including bevacizumab, ramucirumab, pazopanib, lenvatinib, and other anti-angiogenesis inhibitors.
• Has a history and/or has current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vascular system, and lung. Exceptions include calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcifications-these are allowed.
• Has corneal or retinal disorder/keratopathy with current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/ band keratopathy, inflammation, or ulceration, keratoconjunctivitis, or diabetic retinopathy, confirmed by ophthalmic physician. Participants with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
• Are currently receiving or are planning to receive during participation in this study, treatment with 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 drug. Moderate CYP3A4 inhibitors are not prohibited but should be avoided. Medications that increase serum phosphorus and/or calcium concentration are prohibited. Medications associated with hyperphosphatemia and/or hypercalcemia adverse events are searchable in the Leximcomp Online Pharmacy \& Formulary available on the Inside MD Anderson Clinical Tools SharePoint site. Participants are not permitted to receive enzyme-inducing anti-epileptic drugs, including carbamazepine, phenytoin, phenobarbital, and primidone.
• Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products containing juice of these fruits within 7 days prior to first dose of study drug.
• Had a Grade 3-4 gastrointestinal bleed within 3 months prior to enrollment.
• Has a history of deep vein thrombosis, pulmonary embolism, or any other thromboembolism, including portal venous thrombosis within 3 months prior to enrollment. Venous port or catheter thrombosis, incidental asymptomatic pulmonary embolism diagnosed on imaging studies, or superficial venous thrombosis are not considered significant and are allowed.
• Has current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants (including direct oral anticoagulants); thrombolytic agents for therapeutic (as opposed to prophylactic) purpose; use of aspirin (> 325 mg/day); or use of clopidogrel (> 75 mg/day). Note: The use of full-dose oral or parenteral anticoagulants for therapeutic purpose is permitted as long as the INR and/or aPTT is within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the patient has been on a stable dose of anticoagulants for ≥ 2 weeks prior to initiation of study treatment. Prophylactic use of anticoagulants is allowed. However, the use of direct oral anticoagulant therapies such as dabigatran and rivaroxaban is not recommended due to bleeding risk.
• Had significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, transient ischemic attack or cerebrovascular accident); unstable arrhythmia; or unstable angina significant cardiovascular disease within 6 months prior to enrollment.
• Has a history of uncontrolled or poorly-controlled hypertension (>150 mmHg systolic or >100 mmHg diastolic).
• Has a history of hypertensive crisis or hypertensive encephalopathy.
• Had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment.
• Has undergone major surgery (including open biopsy, surgical resection, wound revision; or any other major surgery involving entry into a body cavity); or significant traumatic injury within 28 days prior to enrollment; or subcutaneous venous-access-device placement within 7 days prior to enrollment; or anticipates need for major surgical procedure, core biopsy, or other minor surgical procedures during the course of the study. o Note: Placement of a vascular access device should be at least 2 days prior to initiation of study treatment.
• Is receiving chronic antiplatelet therapy, nonsteroidal anti-inflammatory drugs (e.g., ibuprofen, naproxen), dipyridamole, clopidogrel, or similar agents. Once-daily aspirin use (≤325 mg/day) is allowed.
• Has had significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to randomization.
• Has a history of central nervous system disease or evidence of this disease upon physical or neurological examination.
• Has a history of Grade ≥ 2 hemoptysis (defined as ≥ 2.5 mL of bright red blood per episode) within 1 month prior to screening.
• Has a history or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation).
• Has a history of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess, or active GI bleeding within 6 months prior to randomization.
• Has a history of leptomeningeal disease.
• Has uncontrolled tumor-related pain.
• Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Participants should have recovered from the effects of radiation. There is no required minimum recovery period.
• Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy, if appropriate, prior to enrollment.

Where it is running

• MD Anderson Cancer Center — Houston, Texas, United States (enrolling)

Full record on ClinicalTrials.gov

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