Investigational Drug
Tegavivint
TrialFetch AI Analysis
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Overview
Tegavivint (tegatrabetan; APL-121; BC-2059) is an investigational, intravenously administered small molecule targeting aberrant Wnt/β-catenin signaling. Early clinical studies have evaluated it in desmoid tumors, advanced hepatocellular carcinoma (HCC), pediatric solid tumors and hematologic malignancies, and in combination with osimertinib for EGFR-mutated non–small-cell lung cancer (NSCLC). Available efficacy evidence is preliminary and comes primarily from small, nonrandomized phase 1/2 studies reported as conference abstracts.
Mechanism of action
Tegavivint binds transducin β-like protein 1 (TBL1/TBL1X and TBL1XR1), disrupting the TBL1–β-catenin transcriptional complex. This selectively promotes degradation of nuclear β-catenin and suppresses β-catenin-dependent oncogenic transcription, while aiming to preserve β-catenin’s cytoplasmic and membrane functions. Preclinical activity has been reported across several Wnt/β-catenin-driven tumor models. (aacrjournals.org)
Efficacy
- Desmoid tumors: In a phase 1 study of 24 adults with progressive, unresectable disease, the objective response rate (ORR) was 17% across all doses and 25% at the recommended phase 2 dose of 5 mg/kg. Median response duration was 8.1 months, with responses ongoing at data cutoff. Nine-month progression-free survival was 76% overall and 79% at the recommended dose. (openalex.org)
- Advanced HCC: In an ongoing phase 1/2 monotherapy study, 39 previously treated patients had been enrolled as of January 21, 2026. Among 18 efficacy-evaluable patients with Wnt-pathway mutations treated within the recommended dose range, those with no more than three previous treatment lines had an ORR of 22%, disease-control rate of 89%, and median progression-free survival of 8 months. No objective responses were reported among more heavily pretreated patients, and no significant benefit was observed in patients without Wnt-pathway mutations. (asco.org)
- EGFR-mutated NSCLC: In a 15-patient phase 1b study of first-line tegavivint plus osimertinib, the ORR was 73%, including complete responses in 2 patients (13%); median progression-free survival was 20.6 months. Because the trial was small and lacked a control arm, the contribution of tegavivint beyond osimertinib cannot yet be established. (asco.org)
Safety
In the desmoid-tumor study, common treatment-related adverse events included fatigue (71%), headache (38%), nausea (33%), constipation, decreased appetite and dysgeusia. Five patients experienced separate grade 3 events; no grade 4–5 events or dose-limiting toxicities were reported. (openalex.org)
In HCC, dose-limiting grade 3 anemia occurred in 2 of 5 patients at 8 mg/kg, leading to a recommended range of 3–6.5 mg/kg. Frequent treatment-related events included fatigue, reversible hyperbilirubinemia, reversible anemia, myalgia and decreased appetite. (asco.org)
No dose-limiting toxicities or drug-related serious adverse events were reported with tegavivint plus osimertinib; observed hematologic, dermatologic and gastrointestinal toxicities were described as consistent with osimertinib’s established profile. (asco.org)
Further reading
- Phase 1 desmoid-tumor results
- Phase 1/2 advanced-HCC results
- Phase 1b osimertinib combination results
- Mechanistic study of TBL1 targeting
- Peer-reviewed osteosarcoma preclinical study
Last updated: Sep 2026
Active trials using Tegavivint
Found 4 active trials using this drug:
TrialFetch AI summary: Adults with measurable metastatic colorectal adenocarcinoma that has progressed after, or is intolerant to, at least two systemic therapy lines receive IV tegavivint alone or with unspecified standard-of-care regimens. Tegavivint inhibits Wnt/β-catenin signaling by binding TBL1 proteins and disrupting β-catenin-dependent transcription.
ClinicalTrials.gov ID: NCT07463599
TrialFetch AI summary: Patients with relapsed or refractory osteosarcoma previously treated with at least three standard agents receive intravenous tegavivint plus gemcitabine; the expansion cohort also permits patients with no imaging evidence of disease after pulmonary metastasectomy. Tegavivint inhibits TBL1, disrupting its interaction with β-catenin to suppress oncogenic transcription.
ClinicalTrials.gov ID: NCT07144254
TrialFetch AI summary: Adults with metastatic EGFR exon 19 deletion– or L858R-mutant NSCLC who have not received an EGFR tyrosine kinase inhibitor receive first-line osimertinib plus investigational tegavivint, followed by osimertinib alone. Tegavivint inhibits Wnt/β-catenin signaling by binding TBL1 proteins.
ClinicalTrials.gov ID: NCT04780568
TrialFetch AI summary: This single-arm study enrolls patients aged 1–21 with recurrent or refractory solid tumors, non-Hodgkin lymphoma, or desmoid tumors, with expansion cohorts for selected tumors and Wnt-pathway aberrations extending eligibility to age 30. Patients receive IV tegavivint on days 1, 8, and 15 of each 28-day cycle; it targets TBL1 to disrupt β-catenin–dependent Wnt signaling.
ClinicalTrials.gov ID: NCT04851119
