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NewsResearchers are targeting the "persister cells" that survive standard EGFR-targeted therapy in non-small cell lung cancer (NSCLC). A phase 1b trial found that adding tegavivint — a β-catenin pathway inhibitor — to the standard drug osimertinib produced a 79% response rate with a favorable safety profile, offering early hope for deeper, more durable remissions in first-line EGFR-mutated NSCLC.
One of the biggest frustrations in treating EGFR-mutated non-small cell lung cancer (NSCLC) is that even when targeted therapies work, some tumor cells survive in a dormant "persister" state — eventually fueling resistance and relapse. A new phase 1b trial is testing whether blocking the β-catenin signaling pathway, which drives this persistence, can change that story.
The study combined tegavivint (a selective β-catenin inhibitor) with osimertinib (the standard first-line EGFR inhibitor) in 19 patients with metastatic EGFR-mutated NSCLC. Results presented at the 2026 ASCO Annual Meeting showed an objective response rate of 79%, including complete responses in 3 patients. Notably, the enrolled population had higher rates of CNS and liver metastases and greater tumor burden than typical phase 3 trial populations — making the results even more striking. The combination was well tolerated, with no dose-limiting toxicities or drug-related serious adverse events.
By the Numbers:
Why it matters: Drug-tolerant persister cells are a key driver of treatment failure in targeted cancer therapy. If tegavivint can reliably eliminate these cells alongside osimertinib, it could meaningfully extend remission durations for NSCLC patients — a population that currently faces near-certain disease progression on standard therapy.
