Background: HM95573 is a novel and selective RAF kinase inhibitor which showed potent anti-tumor activities in BRAF, KRAS and NRAS mutant model in vitro and in vivo. This phase 1 trial evaluated the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of HM95573 in patients with solid tumors. Interim results from the phase 1 study are presented here. Methods: Patients who had solid tumor with BRAF, KRAS or NRAS mutation were enrolled. HM95573 was administered everyday with 21-day cycle and treatment cycle has been repeated until disease progression or dose-limiting toxicity (DLT). Dose escalation was performed with PK-guided dose escalation method until target AUC achieved or the first DLT observed. Safety assessments include adverse events (AE), laboratory test, ophthalmologic and dermatological assessments, physical examination, vital signs, and ECG. Serial blood samples were collected on Cycle1Day1, Cycle2Day1, and Cycle3Day1 for PK analysis. Tumor responses were assessed every 6 weeks. Results: Total 31 patients were enrolled in 5 cohorts and doses of each cohort were 50mg QD, 100mg QD, 200mg QD, 200mg BID and 300mg BID. Mean terminal half-life of HM95573 was within the range of 50 to 80 hours after single dosing. However, dose regimen was changed from QD to BID to maximize drug exposure with current formulation. Tumor types from 31 patients were colorectal cancer (68%), melanoma (23%), lung cancer (3%), GIST (3%) and bladder cancer (3%); the BRAF (45%), KRAS (45%) or NRAS (10%) mutation. One patient at 200mg BID experienced grade 3 skin rash as a DLT and up to 300 BID, the maximum tolerated dose was not reached. HM95573 was well tolerated up to 300mg BID; Most of AEs were generally Grade 1 or 2 and most frequent drug-related AE was rash (17%). One patient with NRAS mutant melanoma (200mg QD) experienced an unconfirmed partial response at 12 weeks, and 9 patients had stable disease. Conclusions: Overall, HM95573 was well tolerated up to 300 BID as exposure increased. Preliminary evidence of anti-tumor activity has been observed from 200mg QD, however, current phase 1 study will explore higher doses to evaluate the therapeutic potential of HM95573 further. Clinical trial information: NCT02405065