According to the developer of TTI-101, the REVERT-Liver Cancer trial is the second of three phase 2 trials involving the agent.
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The first 2 patients with locally advanced or metastatic, and unresectable hepatocellular carcinoma (HCC) have been dosed with TTI-101 monotherapy or TTI-101 in combination with standard of care therapy, signaling the initiation of treatment in the experimental arms of the phase 1b/2 REVERT-Liver Cancer trial (NCT05440708).1
TTI-101 is a STAT3 inhibitor being investigated for the treatment of HCC and metastatic breast cancer.1 In a preclinical study of HCC or nonalcoholic steatohepatitis models, STAT3 inhibition achieved in vitro antitumor activity in 3 HCC cell lines.2 Further, phase 1 data from the REVERT-Liver Cancer study showed that TTI-101 monotherapy was tolerable for patients with advanced solid tumors, including HCC, with no dose-limiting toxicities observed.3
Trial Name: 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
ClinicalTrials.gov Identifier: NCT05440708
Sponsor:Tvardi Therapeutics, Inc
Recruitment Contact: Kari Anne Rowland, MS, info@tvardi.com or Sofia de Achaval, PhD, info@tvardi.com
Completion Date: March 2025
In the multicenter, open-label study, approximately 154 patients with advanced HCC will be assessed on treatment with either TTI-101 monotherapy in arm A, TTI-101 plus pembrolizumab (Keytruda) in arm B, or TTI-101 plus atezolizumab (Tecentriq) and bevacizumab (Avastin) in arm C. The coprimary end points being explored in the study are the incidence of adverse events (AEs), the incidence of serious AEs during phase 1b, and overall response rate (ORR) during phase 2. The key secondary end points of the study include ORR, duration of response, disease control rate, duration of disease control, time to tumor progression, best overall response, progression-free survival, and overall survival.4
Eligible patients are those 18 years of age or older with histologically or radiographically confirmed diagnosis of advanced HCC, measurable disease per RECIST v1.1, an ECOG performance status of 0 or 1, and adequate hematologic and organ function. Patients included in cohort A and B must have experienced objective progression on 3 or fewer prior lines of systemic anti-cancer therapy. Those included in cohort C must be treatment naïve, and have been evaluaed for the presence of varices within 6 months prior to initiation of bevacizumab treatment by way of gastroduodenoscopy. . All patients must be willing to use contraception during the study to be eligible for inclusion.
Key information on exlusion of patients in the REVERT-Liver Cancer study shows that patients undergoing treatment for another malignancy are ineligible, as are those previously treated with chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 28 days of the start of study treatment. Patients with certain disease history or active illness may be excluded from the study to avoid interference with the efficacy and safety of the experimental agent, TTI-101.
"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," said Imran Alibhai, PhD, CEO of Tvardi Therapeutics, in a press release.1 "This is the second of three phase 2 trials Tvardi has initiated to address diseases driven by STAT3."
REFERENCES:
1. Tvardi Therapeutics announces first patients dosed in its phase 2 liver cancer trial using TTI-101, a novel STAT3 inhibitor. News release. Tvardi Therapeutics, Inc. June 22, 2023. Accessed June 23, 2023. https://tinyurl.com/5n6c5zbs
2. Jung KH, Yoo W, Stevenson HL, et al. Multifunctional effects of a small-molecule STAT3 inhibitor on NASH and hepatocellular carcinoma in mice. Clin Cancer Res. 2017;15;23(18):5537-5546. doi:10.1158/1078-0432.CCR-16-2253.
3. Tsimberidou AM, Vining DJ, Patel VS, et al. Phase 1 trial evaluating TTI-101, a first-in-class, orally bioavailable, small molecule, inhibitor of STAT3, in patients with advanced solid tumors. J Clin Oncol. 2023;41 (suppl 16):3018. doi:10.1200/JCO.2023.41.16_suppl.3018
4. A study of TTI-101 as monotherapy and in combination in participants with locally advanced or metastatic, and unresectable hepatocellular carcinoma. ClincialTrials.gov. Updated April 26, 2023. Accessed June 23, 2023. https://clinicaltrials.gov/ct2/show/NCT05440708
