Iterion Therapeutics, a Houston-based clinical-stage oncology company, announced that the first patient has been dosed in a Phase I/II clinical trial evaluating tegavivint in metastatic colorectal cancer, according to a company press release issued March 25. Tegavivint is a small-molecule inhibitor of TBL1, a transcriptional co-factor involved in β-catenin signaling, and is described by the company as a first-in-class Wnt/β-catenin inhibitor. No clinical data from the colorectal cancer trial were reported; the announcement pertains solely to the first patient dosing milestone.
The company disclosed no efficacy data, safety data, dosing details, enrollment targets, or study design specifics for the mCRC trial. Iterion stated that the expansion into colorectal cancer builds on what it described as monotherapy activity and a favorable tolerability profile observed in earlier trials in advanced hepatocellular carcinoma and desmoid tumors, including partial responses and disease control in heavily pretreated patients. However, no numerical results from those prior studies were provided in the announcement. Rahul Aras, the company's CEO, characterized the monotherapy activity observed with tegavivint in solid tumors as "unprecedented for a Wnt/β-catenin pathway inhibitor," though the company did not supply supporting data in the release.
The Phase I/II trial (NCT07463599) is being conducted at HonorHealth Research Institute. The patient population consists of individuals with metastatic colorectal cancer, a disease in which the company notes greater than 90% of patients harbor Wnt-pathway activating mutations. No information was provided regarding randomization, blinding, comparator arms, primary endpoints, or planned interim analyses. The trial size, expected duration, and data readout timeline were not disclosed. As only first-patient dosing has occurred, no clinical conclusions can be drawn from this announcement.
Tegavivint inhibits TBL1 to disrupt the TBL1/β-catenin transcriptional complex, promoting degradation of nuclear β-catenin. There are currently no FDA-approved therapies targeting the Wnt/β-catenin pathway in colorectal cancer. In the adjacent indication of advanced hepatocellular carcinoma, established treatments include sorafenib, a multi-kinase inhibitor that demonstrated median overall survival of 10.7 months versus 7.9 months for placebo in the SHARP trial, and the combination of atezolizumab plus bevacizumab, which showed a 12-month overall survival rate of 67.2% versus 54.6% for sorafenib in the IMbrave150 trial. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.
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