A Study of Tegavivint (BC2059) in Patients With Advanced Hepatocellular Carcinoma

NCT05797805 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ITER-002-HCC
• Study Type: interventional
• Target: 178
• Locations: 2 countries
• Sites: 8

Brief Summary

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.

Conditions

Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment-Related Adverse Events

  Adverse events will be assessed according to the NCI-CTCAE version 5.0

  from the date of the first dose of study medication up to 90 days following last dose of study medication or initiation of new systemic anti-cancer therapy, whichever occurs first, an average of 1 year.

• 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.

  Within a 28-day period after first dose of the study medication as a single agent or in combination with cabozantinib or lenvatinib.

• 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)

  Tumors will be assessed at baseline and every 8 weeks until end of treatment, an average of 1 year

Other Outcomes (2)

• Evaluate efficacy of combination of tegavivint plus cabozantinib

  Tumors will be assessed at baseline and every 8 weeks until end of treatment, an average of 1 year

• Evaluate efficacy of combination of tegavivint plus lenvatinib

  Tumors will be assessed at baseline and every 8 weeks until end of treatment, an average of 1 year

Study Arms (3)

Tegavivint single agent dosing regimen

EXPERIMENTAL

Tegavivint as monotherapy

Drug: Tegavivint

Tegavivint plus cabozantinib combination dosing regimen

EXPERIMENTAL

Tegavivint in combination with cabozantinib

Drug: Tegavivint; Drug: Cabozantinib

Tegavivint plus lenvatinib combination dosing regimen

EXPERIMENTAL

Tegavivint in combination with lenvatinib

Drug: Tegavivint; Drug: Lenvatinib

Interventions

Tegavivint DRUG

The 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

Also known as: BC2059

Tegavivint plus cabozantinib combination dosing regimen; Tegavivint plus lenvatinib combination dosing regimen; Tegavivint single agent dosing regimen

Lenvatinib DRUG

In 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 .

Also known as: Lenvima

Tegavivint plus lenvatinib combination dosing regimen

Cabozantinib DRUG

In 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

Also known as: cabometyx

Tegavivint plus cabozantinib combination dosing regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, 18 years of age or older
• Confirmed diagnosis of HCC by either:
• Histologically or cytologically documented HCC based on pathology report or Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria
• 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.
• Measurable disease as defined by RECIST 1.1 with spiral computerized tomography (CT) scan or magnetic resonance imaging (MRI). Lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, may be considered measurable if progression has been demonstrated in such lesions.
• Willingness and ability to provide tumor biopsies during screening and while on treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of the investigational product(s)
• Patients must have organ and marrow function as defined below within 7 days of the first dose of the investigational product(s):
• Absolute neutrophil count (ANC) ≥ 1.2 x 109/L
• Platelets ≥ 60 x 10\^9/L; no transfusion within 7 days prior to assessment
• Hemoglobin ≥ 9 g/dL (red blood cell transfusion or growth factors support is not allowed in the 14 days prior to the screening laboratory assessment)
• Total bilirubin ≤ ULN
• AST and ALT ≤ 5 x ULN

You may not qualify if:

• 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.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tegavivint, or other agents used in study
• 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%

Sponsors & Collaborators

• Iterion Therapeutics: lead

Study Sites (8)

City of Hope

Duarte, California, 91010, United States

RECRUITING

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

UT Southwestern

Dallas, Texas, 75390, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98133, United States

RECRUITING

UHN - Princess Margaret Cancer Centre

Toronto, Ontario, M5G2M9, Canada

RECRUITING

MeSH Terms

Interventions

lenvatinib; cabozantinib

Central Study Contacts

Rose Hernandez

CONTACT

832-721-5208; rose@iteriontx.com

Gilberto Botello

CONTACT

gilberto@iteriontx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2023
• First Posted: April 4, 2023
• Study Start: September 13, 2023
• Primary Completion: May 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 4, 2025

Record last verified: 2025-07

Locations

US (7); CA (1)