A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)

Exclusion Criteria

• •1. Patients who are eligible to be treated with a molecularly targeted therapy on a labelled regimen after receiving first-line chemotherapy. Patients who received a molecularly targeted therapy as part of their first line treatment may be eligible, as determined by the Sponsor Medical Monitor.
• •2. From the time point of screening,
• •1. Less than 4 weeks have elapsed since patients had a surgery or major procedure
• •2. Less than 2 weeks have elapsed from the last treatment date since patients had any radiation therapy
• •3. Patients with percutaneous transhepatic biliary drains (PTBD)
• •4. Prior to the initial treatment of study drug,
• •1. Less than 2 weeks have elapsed since patients had chemotherapy or hormone therapy
• •2. Less than 2 weeks have elapsed since patients had anticancer immunotherapy or investigational drug treatment
• •3. Less than 4 weeks since cryotherapy, radiofrequency ablation, anhydrous alcohol therapy, or photodynamic therapy, including TACE and TARE
• •5. A history of the following cardiovascular diseases (please, consult the Sponsor Medical Monitor for a case by case evaluation):
• •1. Congestive heart failure (CHF) that corresponds to Class II or a higher class under New York Heart Association (NYHA) classification, or less than 50% of left ventricular ejection fraction (LVEF)
• •2. Uncontrolled hypertension (SBP/DBP \>140/90 mmHg) (e.g., patient with SBP/DBP \>140/90 mmHg despite the best care including optimizing the anti-hypertensive medication regimen)
• •3. Patients with any history of hypertensive crisis or pre-existing hypertensive encephalopathy
• •4. Pulmonary hypertension
• •5. Myocardial infarction
• •6. Uncontrolled arrhythmia
• •7. Unstable angina
• •8. Patients with any significant vascular diseases (e.g., aortic aneurysm requiring surgery or recent peripheral artery thrombosis) within 6 months prior to the initial treatment of the investigational product
• •6. 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
• •7. Patients with contraindications to paclitaxel therapy
• •8. 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 v5.0
• •9. Symptomatic or uncontrolled central nervous system (CNS) metastasis (However, patients with asymptomatic CNS metastasis that have been treated with either surgery or radiation 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)
• •10. A history of the following hemorrhage-related or gastroenterological disease:
• •1. Active hemorrhage, hemorrhagic diathesis, coagulopathy or tumor in great arteries
• •2. 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)
• •11. Current or recent (within 10 days prior to study treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose will be excluded.
• •a. Prophylactic (i.e., for the patency of venous access devices) use of low molecular weight heparin (i.e., enoxaparin 40 mg/day) is allowed if patient has INR \< 2 or aPTT \</=2x ULN within 14 days of study treatment
• •12. Patients with current or recent (within 10 days of study treatment) use of aspirin (\>81 mg/day), or other nonsteroidal anti-inflammatory drugs (NSAIDs), or other antiplatelets (i.e., dipyramidole, ticlopidine, clopidogrel, and cilostazol) will be excluded.
• •13. Severe infection requiring ongoing systemic antibiotics, antivirus drugs, etc., or other uncontrolled acute active infectious diseases
• •14. 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.
• •15. 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:
• •1. Pre-existing hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 28 days prior to screening
• •2. Major, unhealed injury, active ulcer, or untreated fracture
• •3. Pre-existing conditions of cerebrovascular incident (ischemic or hemorrhagic stroke), transient ischemic attack or subarachnoid hemorrhage within 6 months prior to screening.
• •4. Moderate to severe ascites and/or pleural effusion. However, enrollment is permitted for patients with ascitic fluid as long as paracentesis is not required to improve the condition.
• •5. Interstitial lung disease or pulmonary fibrosis
• •16. Patients expected to require anticancer treatment other than the investigational product during the clinical study
• •17. Pregnant or lactating patients, or patients planning to become pregnant during the clinical study
• •18. A history of primary malignancy other than BTC will be excluded, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \>90%). Prior malignancy history will be evaluated on a case-by-case basis by the Sponsor Medical Monitor.
• •19. Clinically significant abnormal ECG findings or history determined as clinically significant by the Investigator
• •20. QT interval (Fridericia's formula) (QTcF) interval \> 450msec at the time of screening