2024 World Conference on Lung Cancer (WCLC) - Posters-P3.12D.01 A Phase Ib Study of Osimertinib and Tegavivint as First-Line Therapy in Patients with Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)

P3.12D.01 A Phase Ib Study of Osimertinib and Tegavivint as First-Line Therapy in Patients with Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)

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This document outlines a Phase Ib clinical trial examining the combination of osimertinib and tegavivint as a first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). The study is based on the challenge that EGFR tyrosine kinase inhibitors (TKIs), while initially effective, fail to cure metastatic cancer due to the persistence of drug-tolerant cancer cells influenced by transcriptional changes, notably involving β-catenin.<br /><br />Osimertinib, an EGFR TKI, is combined with tegavivint, which inhibits β-catenin transcriptional activity. The trial follows a single-arm, dose-escalation format using Bayesian optimal interval design, testing four dose levels of tegavivint administered weekly. After initial combined treatment cycles, patients are maintained on osimertinib alone. The dose expansion phase will enroll up to 12 patients at the recommended phase 2 dose.<br /><br />Thirteen patients have been treated without dose-limiting toxicities or serious adverse events related to the drugs. Common mild to moderate side effects include anemia, lymphocytopenia, diarrhea, nausea, and rash, likely attributed to osimertinib.<br /><br />Eligibility criteria include patients with metastatic nonsquamous NSCLC, a classical EGFR mutation, who have not received prior EGFR TKI treatment, and an ECOG performance status of 0-2. Both treated and untreated brain metastases are permitted if the patient is asymptomatic.<br /><br />The trial's primary goals are to assess the safety, tolerability, and recommended phase 2 dose of tegavivint in combination with osimertinib. Secondary and exploratory objectives include evaluating response rates, progression-free survival, pharmacokinetics, and the β-catenin pathway's activity.<br /><br />The study is ongoing at The Ohio State University Comprehensive Cancer Center and is supported by Iterion Therapeutics.

Asset Subtitle

Regan Memmott

Meta Tag

Speaker Regan Memmott

Topic Metastatic NSCLC – Targeted Therapy

Keywords

Phase Ib clinical trial

osimertinib

tegavivint

EGFR-mutant NSCLC

β-catenin

dose-escalation

Bayesian optimal interval design

safety and tolerability

response rates

Ohio State University Comprehensive Cancer Center