Pelitrexol

Abstract: 3075 Background: AG2037 is a rationally designed, novel inhibitor of GARFT, which is an essential enzyme in the de novo synthesis of purines, a critical process for cell growth. Methods: The primary objectives of these studies were to determine the maximum-tolerated dose (MTD) and recommended safe dose of AG2037 for Phase II studies (RP2D). AG2037 was given by bolus or slow iv push (every 3 weeks in Study-002 and weekly for 3 consecutive weeks every 4 weeks in Study-003) to pts with advanced solid tumors in cohorts of at least 3 patients at each dose level. The dose for the next cohort was increased by 100% if no drug related Grade 3 or worse toxicity was encountered, and by ∼50% if Grade 2 toxicity was observed. Results: 45 pts in Study-002 were treated at doses ranging from 1 to 576 mg/m2 and 49 were treated in Study-003 at doses ranging from 1 to 760 mg/m2. Study-002 was terminated before MTD was determined since mechanism-based toxicities appeared to correlate to drug exposure and not to peak concentr...