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A Phase 2 study of Futibatinib 20 mg and 16 mg in Patients with Advanced Cholangiocarcinoma with FGFR2 Fusions or Rearrangements

ClinicalTrials.gov Identifier

NCT05727176

Institution Name

The Gabrail Cancer Center

Institution Address (Street)

4875 Higbee Ave., NW

Institution City

Canton

Institution State

Ohio

Institution ZIP Code

44718

Institution Country

United States

Institution Phone

(330) 492-3345

Additional Institutions

Dr. Parvez Mantry, ParvezMantry@mhd.com The Liver Institute at Methodist Dallas Medical Center 1411 North Beckley Avenue Pavilion III Suite 268 Dallas, TX 75203 Phone: 214-947-4450 Study Coordinator: Uyen Pham, UyenPham@mhd.com

Principal Investigator

Dr. Gabrail

Principal Investigator Phone

(330) 492-3345

Principal Investigator Email

csmith@gabrailcancercenter.com

Study Coordinator

Carrie Smith

Study Coordinator Phone

(330) 492-3345

Study Coordinator Email

csmith@gabrailcancercenter.com

Study Overview

This is a study for patients with advanced, unresectable intra or extrahepatic cholangiocarcinoma (iCCA or eCCA) with fibroblast growth factor receptor FGFR2 fusions or rearrangements. This is an open label study. • There are 2 treatment arms to this study: enrolled patients will receive futibatinib tablets 20 mg or 16 mg

Enrollment Information

120

Study Start Date

20230630

Study End Date

20250630

Study Purpose

The study aims to test how safe the drug is and how well it works against your disease at two different doses. In Arm A, we will confirm the side effects and how well futibatinib works against your disease at 20 mg orally QD. In Arm B, we will learn about the side effects and tolerability and evaluate how well futibatinib at 16 mg orally QD works (iCCA/eCCA) in your disease.

Inclusion Criteria

Histologically or cytologically confirmed, locally advanced, metastatic, or unresectable intrahepatic of extrahepatic Cholangiocarcinoma. Documented evidence of FGFR2 gene fusions or other FGFR2 rearrangement Received at least one prior systemic gemcitabine and platinum-based regimen for CCA Documentation of radiographic disease progression on the most recent prior therapy Measurable disease performance status 0 or 1 Adequate organ function

Exclusion Criteria

History or current evidence of calcium and phosphate homeostasis disorder Current evidence of clinically significant retinal disorder Treatment with any of the following within the specified time frame prior to the first dose of futibatinib: Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of futibatinib) and radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks Patients with locoregional therapy, eg, transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) or ablation within 4 weeks Any non investigational anticancer therapy within 3 weeks or have not recovered from side effects of such therapy prior to futibatinib. Endocrine therapy is allowed for patients with breast or prostate cancer Targeted therapy or immunotherapy within 3 weeks or within 5 half lives Any investigational agent received within 5 half-lives of the drug or 4 weeks, whichever is shorter. Patients with prior FGFR-directed therapy A serious illness or medical condition(s) including (but not limited to) the following: Known brain metastasis (not including primary brain tumors) unless patient is clinically stable for ≥1 month Known acute systemic infection Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV New York Heart Association [NYHA] Classification) within the previous 2 months; if >2 months, cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms Significant gastrointestinal disorder(s) that could interfere with the absorption of futibatinib. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the judgment of the Investigator would make the patient inappropriate for entry into this study. Known additional malignancy that is progressing or requires active treatment, with the exception of patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or antitumor assessment of the investigational regimen. Exceptions must be discussed with the Sponsor prior to patient enrollment. Pregnant or lactating female. Known hypersensitivity or severe reaction to futibatinib or its excipients.

Required Tests Prior to Study

Obtain your medical history, collect pre-existing signs and symptoms, Physical exam, vital signs, height and weight, eye exam, performance status, blood laboratory test for hematology, coagulation, biochemistry, pregnancy test, urine sample, complete patient questionnaire and perform a tumor assessment and MRI

Potential Side Effects

As of January 23, 2022, more than 672 cancer patients have been treated with futibatinib. About 588 of these patients received futibatinib in combination or alone at a starting dose of 20 mg (422 patients) or 16 mg (46 patients) per day. Some possible side effects could be serious, life-threatening, or even fatal. Some side effects may not disappear completely even after you stop taking the study drug. It is recommended that you consume a low-phosphate diet. Diet contains high phosphate included be-low: Fast food, convenience foods, and processed foods may be full of phosphorus additives Beverages that contain phosphorus (look for the letters "phos" in the ingredient list) Also, look for any ingredient that contains "phos" in the term, such as: Calcium phosphate Disodium phosphate Phosphoric acid Monopotassium phosphate Sodium acid pyrophosphate Sodium tripolyphosphate Very Common (at least 1 of every 10 patients) Increased blood levels of phosphate. This may result in muscle cramps, numbness, or tingling around the mouth, but most patients have no symptoms Nail disorders. These might include: Separation of the nail from the skin below, Shedding of the nails, Change in nail color, Infection of the soft tissue around a fingernail, Nail damage, Pain in the nail Diarrhea Hair loss Dry mouth Increased blood level of liver enzymes (ALT and AST). This can be a possible sign of inflam-mation or damage to the liver Dry skin Tiredness and lack of energy Inflammation of the mouth Swelling and redness of the skin on the palms of the hands and soles of the feet Nausea Constipation Reduced desire to eat Changes in taste Dry eye Joint pain Muscle pain Common (at least 1 of every 100 patients) Involuntary contraction (spasm) of a muscle or muscle group Increased blood level of creatinine. This can be a sign of damage to the kidneys Lowered number of a type of blood cell that helps to clot blood Vomiting Lowered weight Retinal disorders. This may include: Damage to the retina. This may lead to possible vision loss Build-up of a fluid at the back of the eye that may lead to impaired vision Separation of the retina from its connection at the back of the eye, which may cause partial blindness Eye damage which may cause vision problems • Lowered number of red blood cells. This may cause tiredness and shortness of breath Blurry vision and vision problems   Increased blood level of an enzyme called alkaline phosphatase. This can be a sign of possible damage to the liver or bone Increased blood level of an enzyme called creatine phosphokinase. This can be a sign of possible muscle damage or muscle breakdown Increased blood level of bilirubin. This may lead to the yellowing of the skin and/or eyes Nerve damage which may include numbness, pain, and/or loss of motor function Itching Eyelashes grow inward toward the eye. The lashes rub against the cornea (front part of the eye), in conjunctiva (the thin, clear, moist part that coats the inner surface of eyelids), the inner surface of the eyelids, or any abnormal or excessive growth Lowered number of white blood cells (neutrophils and lymphocytes). This may increase the risk of infection Increased blood level of calcium. This may result in muscle cramps, confusion, tingling in the lips, and/or stiff, achy muscles Decrease in your normal sensations such as touch or temperature Clouding of the lens of the eye might lead to disturbed vision Chronic heartburn and indigestion Numbness Pain in the hands or feet Abnormal taste Abnormal blood test. This can be a possible sign of heart problems Urinary tract infection Painful red eyes Dehydration. If severe it may require medication, IV fluids, and/or possibly hospitalization Dizziness Heartburn Shortness of breath Abnormal electrocardiogram (ECG) Bloody nose Low blood levels of sodium, which may cause headaches, confusion, seizures, and/or loss of consciousness Low blood levels of phosphate may cause muscle weakness, bone pain, confusion, or muscle breakdown Teary eyes Mouth blisters or sores Abnormal sensations such as pins and needles Fever Rash Slow heart rate, which can cause dizziness, fainting and tiredness Swollen raised areas on the skin that are intensely itchy (hives) Belly pain, feeling of fullness or tightness Feeling weak and having no energy Severe blisters on the skin Eye discharge Low levels of potassium in the blood which can cause an abnormal heart rate. This could cause an irregular heartbeat, which can be serious and life-threatening Low blood levels of magnesium could cause weakness, muscle cramps, and/or irregular heartbeat Increased risk of bleeding Persistent headache or migraine Muscular weakness Dryness in the nose Throat inflammation or pain Cracks in the skin that form may bleed or be painful Involuntary, rhythmic muscle contraction leading to shaking movements in one or more parts of the body In addition, the following uncommon (≥ 0.1% and < 1%) or rare (≥ 0.01% and < 0.1%) severe or signif-icant possible side effects have been reported. Painful or abnormal sensations in the mouth A vague feeling of bodily discomfort or lack of energy Increased risk of infection Fainting Inflammation of the lungs can cause shortness of breath and difficulty breathing High blood pressure

Financial Assistance Available

Yes