REVERT- Liver Cancer: A Phase 1b/2 Multicenter, Open-label Study to Evaluate the Safety and Efficacy of TTI-101 as Monotherapy and in Combination in Participants With Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma

Tvardi Therapeutics, Incorporated

Summary

The primary objectives of Cohort A Phase 1b and exploratory expansion are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent to participants with locally advanced or metastatic, and unresectable Hepatocellular Carcinoma (HCC) and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of TTI-101 as a single agent. The primary objectives of Cohort A Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 as a single agent in participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohort A Phase 2 are to assess response, progression, survival, and pharmacokinetics. The primary objectives of Cohorts B and C Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, or unresectable HCC and to determine the MTD and/or RP2D of TTI-101 when used in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C). The primary objectives of Cohorts B and C Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohorts B and C Phase 2 are to assess response, progression, survival, and pharmacokinetics.

Eligibility

Age range: 18+ years
Sex: All
Healthy volunteers: No

Detailed criteria

Inclusion Criteria: 1. Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions. 2. Age ≥18 years at the time of informed consent. 3. Have histologically or radiographically (Liver Imaging Reporting and Data Systems category 5) confirmed diagnosis of locally advanced or metastatic, and unresectable HCC. Participants without cirrhosis require histological confirmation. 4. Cohorts A and B only: Willing to provide a representative fresh tumor tissue specimen prior to enrollment. The fresh tumor specimen must be obtained after progre…

Interventions

Drug
TTI-101
Oral tablet
Drug
Pembrolizumab
Intravenous (IV) infusion
Drug
Atezolizumab
Intravenous (IV) infusion
Drug
Bevacizumab
Intravenous (IV) infusion

Locations (21)

The Kirklin Clinic of University of Alabama Birmingham Hospital
Birmingham, Alabama
klsaxton@uabmc.edu 205-767-7914
University of California San Diego
La Jolla, California
Norris Comprehensive Cancer Center
Los Angeles, California
Rabia.Rehman@med.usc.edu
University of California Irvine Medical Center
Orange, California
ucstudy@hs.uci.edu 877-827-8839
University of Colorado Hospital - Anschutz Medical Campus
Aurora, Colorado
Jeniffer.choi@cuanschutz.edu 303-724-9833
Georgetown Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia