Lunbotinib (A400/EP0031) selective RET inhibitor posts 81–87% ORR and 27.5-mo mPFS in RET-fusion NSCLC

Lunbotinib is an oral, brain-penetrant next-generation selective RET inhibitor designed to inhibit RET fusion and mutant proteins, evaluated in a pivotal Phase II, two-cohort, single-arm study in China (NCT05265091) at 90 mg QD in previously treated (post platinum + immunotherapy) and treatment-naïve advanced RET fusion–positive NSCLC. At the Oct 29, 2025 cutoff, IRC-confirmed ORR was 87.1% in pre-treated patients (n=70 FAS) with mDoR 25.7 months and mPFS 27.5 months, while ORR was 81.3% in treatment-naïve patients (n=91 FAS) with mDoR not reached and mPFS not reached (lower CI 19.4 months); these efficacy figures land at/above the top end of the established selective RET TKI benchmarks in this setting (e.g., selpercatinib ORR ~64–85% with mPFS ~19–22 months across key LIBRETTO-001 datasets; pralsetinib ORR ~64% with mPFS ~16 months in ARROW). Safety showed near-universal TRAEs (98.8%) with grade ≥3 TRAEs in 40.5% and discontinuations in 1.2%; common TRAEs included transaminitis (AST 72.4%, ALT 68.1%), anemia (63.2%), urinary retention (45.4%), dry eye (43.6%), and creatinine increase (42.9%), and no fatal TRAEs were reported—while SOC selective RET TKIs are guideline-preferred, this particular urinary retention/dry eye signal stands out as a potential differentiator to watch versus the established class toxicity mix (hypertension/transaminitis/QT).