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

NCT06439485 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-0106NCI-2024-04693
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Advanced Cholangiocarcinoma; FGFR2 Fusion

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (2)

Part 1

EXPERIMENTAL

Participants enrolled in Part 1, the dose of pemigatinib the participant receive will depend on when the participant join this study. Up to 2 dose levels of pemigatinib will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the highest dose level of pemigatinib. A second group will receive a lower dose of pemigatinib than the group before it, if intolerable side effects are seen.

Drug: Pemigatinib; Drug: Atezolizumab; Drug: Bevacizumab

Part 2

EXPERIMENTAL

Participants in Part 2, you will receive pemigatinib at the recommended dose that was found in Part 1.

Drug: Pemigatinib; Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Pemigatinib DRUG

Given by PO

Part 1; Part 2

Atezolizumab DRUG

Given by PO and IV

Also known as: MPDL3280A, TECENTRIQ

Part 1; Part 2

Bevacizumab DRUG

Given by PO and IV

Also known as: Avastin™, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Part 1; Part 2

Eligibility Criteria

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

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:

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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Incyte Corporation: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

pemigatinib; atezolizumab; Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sunyoung Lee, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sunyoung Lee, MD,PHD

CONTACT

(713) 792-2828; GIClinicalTrials@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2024
• First Posted: June 3, 2024
• Study Start: November 19, 2024
• Primary Completion (Estimated): February 22, 2028
• Study Completion (Estimated): February 22, 2030
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

US (1)