A phase I trial of PEGylated glutaminase (PEG-PGA) in combination with 6-diazo-5-oxo-L-norleucine (DON) in advanced, refractory, solid tumors

14040 Background: Tumor cells are avid glutamine consumers and highly dependent on extracellular glutamine supply. Based on a competitive mechanism, the effectiveness of the glutamine analogue DON is enhanced if the available pool of glutamine is significantly (below 10% of baseline) depleted by PEG-PGA. Methods: The study was designed to determine the maximal tolerable dose (MTD) of DON in combination with PEG-PGA. The patients received intravenous PEG-PGA 120 I.U./m2 in combination with DON twice weekly for six weeks followed by a tumor assessment according to RECIST. DON dose was escalated from 5 to 185 mg/m2 using modified Fibonacci design and traditional 3-patient cohorts. Results: Fifty-eight pts (23f/35m) received at least 1 drug administration and were evaluable for the analysis. Median age was 62 (range 43–79) and median Karnofsky PS was 90% (range 70%-100%). Median treatment duration was 29 days (range 1–106). Nausea and vomiting represented the most common non-hematological grade 3 toxicities, ...