Final report of a phase I study of 2-hydroxyoleic acid (2OHOA) a novel sphingomyelin synthase activator in patients (pt) with advanced solid tumors (AST) including recurrent high grade gliomas (rHGG).

2554Background: 2OHOA is an orally bioavailable, first-in-class synthetic hydroxylated fatty acid, that activates SGMS1 and modulates the lipid content of cancer cell membranes. This regulates the localization of key signaling proteins, including Ras and PKC at the plasma membrane, leading to inactivation of Ras/MAPK, PI3K/Akt and PKC/cyclin/CDK signaling pathways. A dose escalation (DE) and partial expansion cohorts (EC) results of the phase 1 study have previously been reported. We now present the final results of the study. Methods: 2OHOA was evaluated in a 3+3 DE design (7 cohorts from 500mg/d to 16000mg/d) and 2 EC at 4000mg TID in 21 days cycles. PK profiles were determined after single dose (fasted [D-7] or fed [D1]) and multiple doses (fed [D21]) during DE phase and only on D1 throughout EC.Safety assessments were based on CTCAEv4.Tumor response was measured by RECIST and RANO every 6 weeks. Results: Overall 54 pt (DE: 32 pt; 21AST/11rHGG; EC: 22 pt; 12 AST/10 rHGG) were treated (median age 60, ra...