Background: Trametinib (T), an orally available MEK 1/2 inhibitor, is FDA approved for BRAF^V600E/K mutant advanced melanoma, at the single agent RP2D of 2 mg QD. Its clinical development has involved a variety of refractory cancers. A phase I study was conducted to establish the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and pharmacokinetic (PK) profile of T in advanced solid tumor patients (pts) with varying degrees of hepatic dysfunction (HD). Methods: Advanced cancer pts with ECOG ≤2, adequate renal and bone marrow functions, were stratified (NCI ODWG Criteria) into 4 HD groups: normal (NO), mild (ML), moderate (MD), severe (SV). T was given QD on a 28-days cycle, with dose escalation occurring in sequential cohorts of pts within each HD group (starting dose: NO, ML: 2mg; MD: 1.5 mg; SV: 1mg). PK samples were collected at days 15-16 in cycle 1. Results: Between Mar '14-Nov '15, 30 (17 NO, 7 ML, 3 MD, 3SV) pts were treated. Median age 60, male 43%, ECOG≤1: 97%. Common tumor types: GI non-CRC 17%, NSCLC 17%, uveal melanoma 13%. All cohorts drug-related AEs (All Grades/Grade 3-4): skin rash 73%/7%, increased transaminases 43%/7%, fatigue 40%/7%. No DLTs so far occurred in ML, MD and SV groups. Dose delay and dose reduction occurred in 47% and 20% of all pts respectively. PK data were available in 10 NO and 6 ML HD cohort pts (Table). Of 23 pts evaluable for response, 13 (56%) had stable disease and 2 (9%) pts partial response (NSCLC; ovarian). Median duration of response was 3.6 months (range 1-13.7+). Conclusions: The RP2D for trametinib in ML group, which has completed accrual, is 2 mg QD. The PK profile in NO and ML groups is comparable. Thus far, T appeared to be tolerated within all groups. Accrual in MD and SV groups is ongoing at 1.5 mg QD and 1 mg QD respectively. Clinical trial information: NCT02070549