Comparing 3 approaches for advanced hepatocellular carcinoma

Exclusion

• −History of allergic reactions attributed to compounds of similar chemical or biologic composition to tegavivint, or other agents used in study
• −Hypersensitivity or intolerance to cabozantinib (patients with hypersensitivity or intolerance to cabozantinib may enroll in treatment armsArmOne of the groups in a study, each receiving something different.Read more → exploring tegavivint plus lenvatinib if they did not have hypersensitivity or intolerance to lenvatinib).
• −Hypersensitivity or intolerance to lenvatinib (patients with hypersensitivity or intolerance to lenvatinib may enroll in treatment arms exploring tegavivint plus cabozantinib if they did not have prior hypersensitivity or intolerance to cabozantinib)
• −Ongoing or active infection (exception: HBV infection - see inclusion criteriaInclusion criteriaThe things you must have or be for a study to consider you.Read more →)
• −HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PKPharmacokineticsThe study of how the body absorbs, distributes, and clears a treatment.Read more → interactions with tegavivint.
• −Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• −Patients receiving therapy with other anti-neoplastic or experimental agents
• −Patients receiving concomitant strong inhibitors of CYP3A4/5 that cannot be discontinued 7 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1.
• −Patients receiving concomitant inducers of CYP3A4/5 that cannot be discontinued at least 14 days prior to Cycle 1 Day 1.
• −Patients with known history of Gilbert's syndrome or other genetic conditions affecting UGT1A1 function.
• −Malignant disease, other than that being treated in this study. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded. Other exceptions include malignancies that were treated curatively and have not recurred within 3 years prior to Cycle 1 Day 1 and any malignancy considered indolent and that has never required therapy.
• −Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples
• −Known central nervous system (CNS) involvement
• −Uncontrolled concurrent illness including, but not limited to:
• −Unhealed wounds or presence of any external drainage
• −Psychiatric illness/social situations that would limit compliance with study requirements; discuss with Medical Monitor if there are any questions
• −Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
• −Congestive heart failure, NYHA \> Class II
• −Left ventricular ejection fraction \< 50%
• −Unstable angina pectoris or cardiac arrhythmia
• −BaselineBaselineYour starting measurements, taken before treatment begins.Read more → QTc (Fridericia) ≥ 450 milliseconds. In the event a QTc (Fridericia) measurement is not possible due to factors such as a pacemaker or bundle branch block, the patient may be evaluated by a cardiologist who must document no apparent increased risk for Torsades de Point or other morbidity associated with prolonged QTc. With such documentation, the patient may be eligible based with additional Medical Monitor review.
• −Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome
• −Myocardial infarct within 6 months before Cycle 1 Day 1
• −Clinically significant pericardial disease
• −Exclusions for patients treated on study with cabozantinib or lenvatinib:
• −Patients with large esophageal varices at risk of bleeding that are not being treated with conventional medical intervention: beta blockers or endoscopic treatment. Assessment of esophageal varices for patients in whom conventional medical intervention for known esophageal varices is already in place should be performed by endoscopy as per local standard of careStandard of careThe treatment normally given for a condition outside a study.Read more →.
• −Uncontrolled hypertension (systolic blood pressure \>150 mmHg or diastolic pressure \>90 mmHg despite optimal medical management).
• −Persistent proteinuria of NCI-CTCAE version 5.0 grade 3 or higher. Urine dipstick result of 3+ is allowed if protein excretion (estimated by urine protein/creatinine ratio on a random urine sample) is \<3.5 g/24 hours.
• −Clinically significant bleeding NCI-CTCAE version 5.0 grade ≥ 3 within 30 days before randomizationRandomisedWhich group you go into is decided by chance, not by you or your doctor.Read more →.
• −Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months before the start of study medication.
• −Patients treated with medications with a known potential to prolong the QT/QTc interval.
• −Pregnant and breastfeeding women are excluded from this study. The effects of tegavivint on the developing human fetus have the potential for teratogenic or abortifacient effects. There is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with tegavivint
• −Women of child-bearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use one highly effective method of contraception, including hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device or intrauterine system; vasectomy or tubal ligation; and one effective method of contraception, including male condom, female condom, cervical cap, diaphragm or contraceptive sponge or abstaining from sex for the duration of study participation and for at least 4 months following completion of tegavivint and pembrolizumab (if applicable) administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• −Any major surgery within 21 days prior to Cycle 1 Day 1. Major surgery is defined as any significantly invasive procedure into a major body cavity (abdomen, cranium etc.) and/or surgery requiring extensive recuperation (joint replacement). Please discuss with the Medical Monitor if there are any questions.