Source – Tvardi Therapeutics
On June 22, 2023 the initial administration of TTI-101, either as a monotherapy or in combination with standard care therapy, commenced for the first two patients with locally advanced or metastatic, unresectable hepatocellular carcinoma (HCC). This marks the beginning of treatment in two out of three experimental arms of the REVERT-Liver Cancer trial (NCT05440708), a Phase Ib/II study.
TTI-101 is a STAT3 inhibitor currently being investigated for the treatment of HCC and metastatic breast cancer. Preclinical studies have demonstrated promising antitumor activity of STAT3 inhibition in HCC cell lines derived from HCC or nonalcoholic steatohepatitis models. In phase 1 data from the REVERT-Liver Cancer trial, TTI-101 monotherapy was found to be well-tolerated among patients with advanced solid tumors, including HCC, without any observed dose-limiting toxicities.
The multicenter, open-label study aims to evaluate approximately 154 patients with advanced HCC who will receive treatment in one of three arms: TTI-101 monotherapy (arm A), TTI-101 plus pembrolizumab (Keytruda) (arm B), or TTI-101 plus atezolizumab (Tecentriq) and bevacizumab (Avastin) (arm C). The study will assess several endpoints, including the incidence of adverse events and serious adverse events during phase 1b, as well as the overall response rate during Phase II. Additional secondary endpoints include duration of response, disease control rate, time to tumor progression, best overall response, progression-free survival, and overall survival.
Eligible participants must be 18 years of age or older and have a histologically or radiographically confirmed diagnosis of advanced HCC, measurable disease according to RECIST criteria, an ECOG performance status of 0 or 1, and adequate hematologic and organ function. Patients in cohorts A and B should have experienced objective progression on three or fewer prior lines of systemic anti-cancer therapy, while those in cohort C must be treatment-naïve and exhibit varices during screening. Additionally, all patients must agree to use contraception during the study to be included in the trial.
“Enthusiasm for our HCC study continues to expand with recently presented clinical data demonstrating TTI-101 monotherapy has robust efficacy in heavily pretreated patients with HCC, published preclinical work highlighting TTI-101’s synergy with immunotherapy, and the FDA’s Fast-Track Designation for TTI-101 in HCC. This is the second of three Phase II trials Tvardi has initiated to address diseases driven by STAT3.”
– Imran Alibhai, PhD, CEO of Tvardi Therapeutics
The REVERT-Liver Cancer study has specific exclusion criteria in place. Patients undergoing treatment for another malignancy and those who have received chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 28 days prior to the start of the study treatment are ineligible. Patients with certain disease history or active illnesses may also be excluded to ensure the efficacy and safety of TTI-101 as an experimental agent.
