Osimertinib + tegavivint (β-catenin/TBL1 transcription inhibitor) posts 73% ORR and 20.6-mo mPFS in 1L EGFR-mutant NSCLC

Osimertinib (3rd-gen EGFR TKI) was combined with tegavivint, an IV Wnt/β-catenin pathway inhibitor that blocks β-catenin transcriptional activity via TBL1 binding, in a single-arm Phase Ib dose-escalation trial in previously EGFR TKI–naïve metastatic EGFR exon 19 del/L858R NSCLC (n=15 evaluable; NCT04780568). The RP2D was tegavivint 8 mg/kg weekly IV for 16 weeks with osimertinib 80mg daily; no DLTs or drug-related SAEs were reported, and AEs were mainly hematologic/skin/GI consistent with known osimertinib toxicity. Efficacy showed ORR 73% with CR 13% and median PFS 20.6 months (95% CI 7–32), which lands in the same neighborhood as historical 1L osimertinib benchmarks (FLAURA: ORR ~80%, median PFS 18.9 months) rather than clearly exceeding them, though OS is immature.