Preliminary Phase 1 clinical data for OP-3136, a potent lysine acetyltransferase 6 (KAT6) inhibitor, demonstrated acceptable tolerability and promising anti-tumor activity. The study evaluated OP-3136 monotherapy in 32 heavily pretreated patients with ER+/HER2advanced breast cancer (ABC), metastatic castration-resistant prostate cancer (mCRPC), and metastatic non-small cell lung cancer (mNSCLC). OP-3136 monotherapy was well-tolerated with no dose-limiting toxicities observed across daily doses up to 45 mg. Most treatment-related adverse events (TRAEs) were Grade 1 or 2, with no Grade 4 or 5 TRAEs, and no treatment discontinuations occurred due to TRAEs. Tumor shrinkage was observed in 13 out of 19 response-evaluable patients, with 3 partial responses (2 confirmed, 1 unconfirmed) in patients with measurable disease. The longest duration of treatment was 62 weeks, and 11 patients remain on treatment, including 9 with ABC and 2 with mCRPC. OP-3136 demonstrated rapid, sustained, and significant reduction in levels of lysine 23 of histone H3, consistent with on-target KAT6 inhibition. Pharmacokinetics showed predictable, dose-proportional plasma exposure, with steady-state concentrations exceeding efficacy targets based on preclinical models at doses of 6 mg and above.