Iterion Therapeutics Reports Positive Tegavivint Phase 1b Data

Houston, Texas, U.S., September 22, 2026

Tegavivint Shows Early Antitumor Activity

The Phase 1b study, designated NCT04780568, was conducted at The Ohio State University Comprehensive Cancer Center and enrolled patients with metastatic EGFR-mutated NSCLC who had not previously received an EGFR tyrosine kinase inhibitor. The dose-escalation portion included 15 evaluable patients, while four additional patients were enrolled in a dose-expansion cohort at the highest dose. Participants received osimertinib 80 mg once daily together with weekly intravenous tegavivint at doses ranging from 3 to 8 mg/kg during the initial treatment period. The recommended Phase 2 dose was identified as 8 mg/kg.

Across all evaluable patients, the combination generated an ORR of 79%, including complete responses in 3 of 19 patients (16%). In the dose-escalation cohort, the reported median progression-free survival (PFS) was 19.9 months, while median overall survival (OS) was 48.8 months, although the OS analysis remains limited by the small number of events. Earlier ASCO 2026 data from the dose-escalation population reported an ORR of 73%, two complete responses among 15 evaluable patients and median PFS of 20.6 months, illustrating that the dataset has continued to mature as additional patients were evaluated.

Targeting Drug-Tolerant Cancer Cells

The scientific rationale for combining tegavivint with osimertinib centers on a persistent challenge in EGFR-mutated NSCLC. Although EGFR tyrosine kinase inhibitors can produce substantial tumor responses, some cancer cells can enter a drug-tolerant persister state, allowing them to survive treatment and potentially contribute to subsequent disease progression and resistance. Preclinical research has implicated increased β-catenin transcriptional activity in this persistent state.

Tegavivint is designed to inhibit β-catenin transcriptional activity by binding to TBL1, a protein involved in nuclear β-catenin signaling. By disrupting this pathway, the investigational therapy is intended to suppress genes involved in tumor growth, cancer-cell survival and treatment resistance. The combination strategy therefore aims to complement osimertinib’s EGFR inhibition by targeting a biological mechanism that may allow residual tumor cells to persist despite EGFR blockade. Preclinical studies reported by the investigators showed deeper and longer-lasting responses when an EGFR inhibitor was combined with β-catenin pathway inhibition.

Combination Demonstrates Favorable Tolerability

The Phase 1b combination was reported to have a favorable safety profile, with no dose-limiting toxicities, drug-related serious adverse events, Grade 4 or 5 adverse events, or pneumonitis of any grade. The most frequently reported drug-related adverse events included diarrhea, maculopapular rash, anemia and fatigue, with most events being Grade 1 or Grade 2. Pharmacokinetic analyses showed dose-proportional exposure to tegavivint and no evidence of a clinically meaningful drug-drug interaction with osimertinib.

The findings provide early clinical evidence supporting the investigation of β-catenin pathway inhibition as a complementary strategy to EGFR-targeted treatment. However, the study is an early-stage, single-arm Phase 1b trial involving a relatively small number of patients, so the reported efficacy findings require confirmation in larger controlled studies. The companies and investigators will continue evaluating tegavivint’s potential in EGFR-mutated NSCLC and other cancers driven by abnormal Wnt/β-catenin signaling.

Source: Iterion Therapeutics press release