Tegavivint May Be Safe and Tolerable for Treatment of Desmoid Tumors

Treatment with the novel, potent, and selective nuclear beta-catenin inhibitor, tegavivint (BC2059), did not lead to any dose-limiting toxicities (DLTs) or significant adverse events (AEs) in patients with desmoid tumors in a phase 1 study (NCT03459469), confirming the safety of the agent, according to a press release from Interion Therapeutics, Inc.

Based on the safety findings, tegavivint will be investigated in other diseases in which nuclear beta-catenin signaling has been identified as a potential therapeutic target, including acute myeloid leukemia, non–small cell lung cancer, and some pediatric cancers. The investigation will be initiated late in 2021. Investigators were also able to determine the recommended phase 2 dose (RP2D) of tegavivint as treatment of patients with desmid tumors based on the pharmacokinetic properties and clinical responses observed. The RP2D was then administered to 16 patients in the study.

"We have seen very good tolerability with no dose-limiting toxicities and no significant adverse events in escalating clinical doses," said Casey Cunningham, chief medical officer of Iterion, in a press release. "We are seeing a very strong safety signal in patients who have been on tegavivint for over a year and are also observing tumor activity in patients. We continue to follow the patients that are still receiving treatment and look forward to sharing efficacy results at an upcoming medical conference."

Tegavivint works by binding to a novel downstream target in the Wnt-signaling pathway known as TBL1. This stops Wnt pathway gene expression without affecting other Wnt/beta-catenin functions in the cell membrane and limits the toxicities often observed with drugs in the Wnt pathway.

For the purposes of the phase 1, open-label, non-randomized study, 24 patients were enrolled who met the requirements of being aged 18 years or older with a histologically proven primary or recurrent desmoid tumor that is measurable and unresectable, an ECOG performance status of 0-1, and adequate laboratory values at baseline. Patients were allowed entry into the study cohort if they had received prior local therapies such as surgery, radiation, radiofrequency ablation, or cryosurgery in the 4 weeks before the study. The study also allowed individuals who received systemic therapies such as cytotoxics, biologics or other unclassified experimental therapies 3 weeks prior to the study. Finally, those who were previously treated with immune therapies such as vaccines, dendritic or other whole-cell therapies, oncolytic, or other viral approaches within 12 months of the start of the study were eligible.

The study excluded patients who had not recovered from a grade 1 AE caused by a prior treatment, allergic reaction to drugs similar to tegavivint, and those with a personal history of malignancy with the exception of cervical intraepithelial neoplasia, Basal cell carcinoma, treated localized prostate carcinoma with prostate-specific antigen <1 ng/mL, or neoplasia treated with curative intent. In addition, those with other conditions that may interfere with study treatment were excluded. These conditions included metabolic bone disease, clinically significant, uncontrolled heart disease or cardiac abnormality, uncontrolled concurrent illness, psychiatric illness,human immunodeficiency virus, and familial adenomatous polyposis. Patients who did not have peripheral venous or central venous access or were pregnant or breastfeeding could not be treated in the clinical trial.

Patients in the study were administered the investigational agent intravenously according to a 3 + 3 dose-escalation design. The primary end point was the safety and tolerability of the agent determined by AEs, serious AE, and DLTs. The secondary end point was the duration of response to tegavivint in patients with desmoid tumors, which was determined after the achievement of a best response of either a complete response or partial response within a 12-month time frame.

_Reference:

_{Iterion Therapeutics confirms safety of tegavivint following completion of enrollment in phase 1/2a expansion study in patients with desmoid tumors. News release. Iterion Therapeutics, Inc. April 13, 2021. Accessed April 14, 2021.}