Tegavivint Phase 1b/2a Trial Begins for Advanced Liver Cancer Patients After Treatment Failure

Iterion Therapeutics, a biopharmaceutical company specializing in cancer treatment, has initiated a Phase 1b/2a clinical trial for its lead drug candidate, tegavivint. The trial is designed to test the drug's efficacy in treating patients with advanced hepatocellular carcinoma (HCC) who have not responded to at least one systemic treatment. Tegavivint targets Transducin beta-like protein 1 (TBL1), a crucial component in the Wnt/beta-catenin signaling pathway, which is often hyperactivated in various cancers, including HCC.
The Wnt/beta-catenin pathway is known for its role in tumor development and progression. Tegavivint's mechanism of action involves binding to TBL1, which leads to the displacement of beta-catenin, a protein that, when stabilized, can activate cancerous genes. By disrupting this interaction, tegavivint aims to degrade free nuclear beta-catenin, thereby inhibiting the transcription of oncogenes and potentially offering a new therapeutic approach for HCC patients with limited treatment options.
Rahul Aras, Ph.D., President and CEO of Iterion Therapeutics, highlighted the drug's potential to inhibit oncogenic activity without causing the toxicities associated with other Wnt-pathway targeting drugs. Hepatocellular carcinoma is a prevalent and aggressive form of cancer, with a 5-year survival rate of 21.6%, according to the National Cancer Institute (NCI). The Wnt pathway is particularly significant in HCC, as it can initiate tumor growth, promote metastasis, and create an immunosuppressive environment within the tumor.
The clinical trial is expected to enroll approximately 35 patients with unresectable locally advanced or metastatic HCC. The study's objectives include assessing the drug's safety, clinical efficacy, pharmacokinetics, and pharmacodynamics to establish a recommended dose for Phase 2 trials. Tegavivint has previously shown safety and activity in a Phase 1 study involving patients with desmoid tumors.
Casey Cunningham, M.D., Chief Medical Officer of Iterion Therapeutics, emphasized the urgent need for new therapies to address the significant unmet medical need in HCC, particularly for patients with Wnt-activated tumors. The ongoing trial aims to provide valuable insights into the drug's potential as a targeted treatment for this patient population.
Iterion Therapeutics is a clinical-stage company focused on developing innovative cancer therapeutics, with tegavivint as its lead product. The company is advancing clinical programs for tegavivint in various cancer indications where nuclear beta-catenin overexpression is a factor, including HCC, non-small cell lung cancer (NSCLC), diffuse large B-cell lymphomas (DLBCL), and pediatric solid tumors. Iterion has received significant funding from the Cancer Prevention and Research Institute of Texas (CPRIT) to support its product development efforts.