A Phase 2/3 Randomized, Controlled Study of CTX-009 in Combination with Paclitaxel Versus Paclitaxel Alone in Adult Patients with Unresectable, Advanced, Metastatic or Recurrent Biliary Tract Cancers Who Have Received One Prior Systemic Chemotherapy Regimen

• Beyond First Line Therapy
• Chemotherapy
• Immunotherapy

Texas Oncology – Denison
Denison, Texas 75020 United States
PI: Dr. Amir Faridi, 903-868-4700, amir.faridi@usoncology.com

New York Oncology Hematology
Albany, New York 12206 United States
PI: Dr. Lawrence Garbo, 518-489-0044, Lawrence.garbo@usoncology.com

Texas Oncology – Dallas (Baylor Charles A. Sammons Cancer Center)
Dallas, Texas 75246 United States
PI: Dr. Andrew Scott Paulson, 214-370-1000, scott.paulson@usoncology.com

Texas Oncology – McAllen
McAllen, Texas 78503 United States
PI: Dr. Suresh Ratnam, 956-687-5150, suresh.ratnam@usoncology.com

Medical Oncology Hematology Consultants
Newark, Delaware 19713 United States
PI: Dr. Jamal Misleh, 302-366-1200, jamal.misleh@usoncology.com

Texas Oncology – Northeast Texas
Tyler, Texas 75702 United States
PI: Dr. Donald Richards, 903-579-9800, Donald.richards@usoncology.com

Prisma Health – Upstate
Greenville, South Carolina, 29605 United States
PI: Dr. Christopher Thomas, 864-241-6251, chris.thomas@prismahealth.org

Northwest Cancer Specialists
Vancouver, Washington 98684 United States
PI: Dr. David Cosgrove, 360-944-9889, David.cosgrove@compassoncology.com

Texas Oncology – Austin
Austin, Texas 78705 United States
PI: Dr. Vivian Cline, 512-421-4100, vivanjean.cline@usoncology.com

Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey 08901 United States
PI: Dr. Howard Hochster, 732-235-5912, howard.hochster@rutgers.edu

• Compare the effects of using CTX-009 along with chemotherapy paclitaxel to using paclitaxel alone in patients with previously treated, unresectable advanced or metastatic biliary tract cancers.

• 18 years of age and older
• Histologically or cytologically confirmed unresectable advanced, metastatic, or recurrent biliary tract cancers (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma)
• Patients must have radiologically documented progression after a prior gemcitabine and platinum containing chemotherapy regimen as initial therapy for locally advanced or metastatic disease. Patients who relapse within 6 months of receiving gemcitabine and platinum containing chemotherapy regimen in the adjuvant setting are also eligible.
• At least one lesion measurable as defined by RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Predicted life expectancy of at least 12 weeks
• No evidence of ongoing infection and adequate biliary excretion or patients whose adequate biliary excretion can be confirmed with the following procedures: Patients who underwent endoscopic retrograde biliary drainage (ERBD) at least 1 week before the investigational drug treatment; Patients who underwent percutaneous transhepatic biliary drainage (PTBD) at least 4 weeks before the investigational drug treatment; Patients free of any signs of active or suspected uncontrolled infection after a drainage procedure; Patients free of any risk of hemorrhage and with incision completely healed
• Adequate bone marrow, hepatic, and renal function within 14 days of randomization as described in the study protocol (Patient must be free of granulocyte colony-stimulating factor (G-CSF) treatment and blood transfusion within 14 days prior to the lab test)
• Female patients who are women of childbearing potential (WCBP) must have a negative pregnancy test (serum-human chorionic gonadotropin (hCG) or urine-hCG performed at the Investigator’s discretion) within 14 days of randomization
• Female patients must be surgically sterile (or have a monogamous partner who is surgically sterile) or be at least 2 years postmenopausal or commit to use 2 acceptable forms of birth control (defined as the use of an intrauterine device (IUD), a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence) for the duration of the study and for 4 months following the last dose of study treatment. Male patients must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study and for 4 months following the last dose of study treatment.
• Signed and dated Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) before any protocol-directed screening procedures are performed

• Patients who are eligible to be treated with a molecularly targeted therapy on a labelled regimen after receiving first-line chemotherapy
• From the time point of screening, Less than 4 weeks have elapsed since patients had a surgery or major procedure and Less than 2 weeks have elapsed from the last treatment date since patients had any radiation therapy
• Prior to the initial treatment of study drug, Less than 2 weeks have elapsed since patients had chemotherapy or hormone therapy (However, patients cannot participate when nitrosoureas or mitomycin was administered within 6 weeks) and/or Less than 2 weeks have elapsed since patients had anticancer immunotherapy or investigational drug treatment and/or Less than 6 weeks since cryotherapy, radiofrequency ablation, anhydrous alcohol therapy, or photodynamic therapy
• A history of cardiovascular disease in the past 5 years as defined in the study protocol
• History of hypersensitivity reactions to any components of the investigational product or other drugs of the same class (humanized/human monoclonal antibody drugs) or paclitaxel
• Patients with contraindications to paclitaxel therapy
• Patients with persistent, clinically significant toxicities (excluding hair loss) from previous anticancer treatment that corresponds to Grade 2 or a higher grade under NCI-CTCAE v5.
• Symptomatic or uncontrolled central nervous system (CNS) metastasis (However, patients with asymptomatic CNS metastasis can participate provided that systemic corticosteroid treatment was discontinued at least 4 weeks prior to screening and that the patient is radiologically and neurologically stable or improving)
• A history of the following hemorrhage-related or gastroenterological disease: Active hemorrhage, hemorrhagic diathesis, coagulopathy or tumor in great arteries and/or History of clinically significant gastroenterological disease, such as peptic ulcer, GI bleeding, GI or non-GI fistula, perforation, abdominal abscess, clinical symptoms, and signs of GI obstruction, need for parenteral hydration or nutrition, or inflammatory bowel disease (IBD)
• Patients who received antiplatelet drugs (aspirin, clopidogrel, etc.) or anticoagulant drugs (warfarin, heparin, etc.) within 2 weeks prior to screening, or is expected to need those drugs during the clinical study
• Patients requiring continuous treatment with systemic non-steroidal anti-inflammatory drugs (NSAIDs) or systemic corticosteroids (the following cases are permitted): NSAIDs: Up to 3 consecutive days’ use is permitted; Corticosteroids: Topical use of corticosteroids, such as topical intra-articular injection, intranasal administration, eye drops, inhaler, etc., or temporary systemic corticosteroid use for treatment and prevention of patient’s contrast media allergy, paclitaxel pre-treatment, or adverse event, is permitted
• Severe infection requiring systemic antibiotics, antivirus drugs, etc., or other uncontrolled acute active infectious diseases
• Patients with evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with positive HBsAg and/or detectable HBV DNA are eligible only if adequately controlled on antiviral therapy according to institutional standards and liver function eligibility criteria are also met. HCV patients showing sustained viral response or patients with immunity to HBV infection may enroll.
• Patients with other severe diseases or uncontrolled illnesses that warrant the exclusion from the study (permitted only if medically controlled) including but not limited to as described in the study protocol
• Patients expected to require anticancer treatment other than the investigational product during the clinical study
• Pregnant or lactating patients, or patients planning to become pregnant during the clinical study
• A history of primary malignant tumor other than biliary tract cancer with the following exceptions: At least 3 years have passed since complete remission of primary malignant tumor (Patients who had papillary thyroid carcinoma and underwent a radical resection may participate in the clinical study even if less than 3 years have elapsed); At least 1 year has passed since complete resection of dermal basal cell carcinoma or successful treatment of cervical intraepithelial neoplasia
• Clinically significant abnormal ECG findings or history determined as clinically significant by the Investigator
• QT interval (Fridericia’s formula) (QTcF) interval > 450msec at the time of screening

• Medical History
• Vital Signs
• ECG (Heart Tracting)
• Echocardiogram
• Physical Exam
• CT or MRI
• Blood and urine samples
• Pregnancy test (if applicable)

• CTX-009 is still being tested in people and the complete side effects may still be unknown. The below is a list of study treatment emergent adverse events observed in ≥ 10% (more than 3 of 24) study participants with biliary tract cancer who received CTX-009 in combination with Paclitaxel:
• Anemia (low red blood count); Neutropenia (low white blood cell count)
• Abdominal pain; Ascites (swelling); Constipation; Diarrhea; Indigestion; Nausea
• Fatigue (tiredness); Fever; Mucosal (the lining of your stomach and intestines); Inflammation; Edema (swelling); Weakness
• Liver abscess (pocket of pus); Liver infection
• Aspartate aminotransferase increased; Blood bilirubin increased; Neutrophil (white blood cells) count decreased; Platelet count decreased
• Decreased appetite
• Muscle pain
• Headache; Neuropathy peripheral (damage to nerves in your body)
• Protein in urine
• Cough; Difficulty speaking; Difficulty breathing; Nosebleed; Pulmonary hypertension (high blood pressure in the lungs)
• Itchy skin
• Hypertension (high blood pressure)