This study will be conducted in 2 parts. The first part is a phase 1 single-agent dose escalation, and dose optimization, study of tegavivint in patients with advanced HCC after failure of at least one line of prior systemic therapy. The second part of the study will begin with a brief dose escalation part for each combination (tegavivint plus cabozantinib or tegavivint plus lenvatinib) followed by a combination dose expansion.
Male or female, 18 years of age or older
Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
Child-Pugh class A or ≤ 7 class B liver score (no hepatic encephalopathy) within 7 days of first dose of the investigational product(s)
Disease progression, intolerance or contraindication to at least one line of systemic therapy for advanced HCC Prior treatment with cabozantinib or lenvatinib is allowed in the combination dose escalation and expansion parts of the study.
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.
Parallel
Tegavivint
DrugThe first part is a phase 1 single-agent dose escalation, optimization, and expansion study of tegavivint in patients with advanced HCC after failure of at least one line of prior systemic therapy. Tegavivint single agent dosing regimen: Tegavivint will be administered weekly on Days 1, 8, 15, and 22 of a 28-day cycle
Lenvatinib
DrugIn the second part of the study, the combination of tegavivint plus lenvatinib will be assessed with a limited dose escalation followed by a randomized dose optimization. Tegavivint plus lenvatinib combination dosing regimen: Tegavivint will be administered weekly on Days 1, 8, and 15 and 22 of a 28-day cycle; lenvatinib 8 mg (patients \< 60 kg) or 12 mg (patients ≥ 60 kg) will be administered once daily on days 1-28 of a 28-day cycle .
Cabozantinib
DrugIn the second part of the study, the combination of tegavivint plus cabozantinib will be assessed with a limited dose escalation followed by a randomized dose optimization. Tegavivint plus cabozantinib combination dosing regimen: Tegavivint will be administered weekly on Days 1, 8, and 15 and 22 of a 28-day cycle; cabozantinib 60 mg (patients with Child-Pugh A) or 40 mg (patients with Child-Pugh B) will be administered orally once daily on days 1 through 28 of each 28-day cycle
Incidence of Treatment-Related Adverse Events
Adverse events will be assessed according to the NCI-CTCAE version 5.0
Number of participants with dose limiting toxicities
Dose limiting toxicities defined as a Grade 3 or greater adverse event as assessed by NCI-CTCAE version 5.0 (excluding toxicities clearly related to the underlying disease \[HCC\], disease progression, concomitant medications, or baseline concurrent medical conditions),and that meets any of the criteria included in Table 6-5.
Evaluate efficacy of tegavivint as a single agent
Evaluate efficacy of tegavivint as a single agent in subjects with hepatocellular carcinoma as assessed by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Evaluate efficacy of combination of tegavivint plus cabozantinib
If sufficient clinical benefit is observed with tegavivint single agent, the efficacy of the combination of tegavivint plus cabozantinib will be evaluated using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Evaluate efficacy of combination of tegavivint plus lenvatinib
If sufficient clinical benefit is observed with tegavivint single agent, the efficacy of the combination of tegavivint plus lenvatinib will be evaluated using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Click on the lead sponsor to view all of their trials.
