Phase I Study Of Adi-Peg 20 In Combination With Pemetrexed And Cisplatin (Trap) In Patients With Ass1-Deficient Mesothelioma And Non-Squamous Lung Cancer.

TPS2612 Background: Loss of the metabolic tumor suppressor, argininosuccinate synthetase (ASS1), a rate-limiting enzyme in arginine biosynthesis, sensitizes mesothelioma and lung carcinoma cells to apoptosis following arginine withdrawal. Recently, we showed potentiation of the cytotoxic effect of pemetrexed by the arginine depletor pegylated arginine deiminase (ADI-PEG 20) in ASS1-negative tumor cells, which was accompanied by suppression of de novo pyrimidine synthesis and the pyrimidine salvage pathway (Allen et al, Cancer Res 2014). Consequently, we have initiated a phase I study (NCT02029690) to assess the maximum tolerated dose (MTD), safety and toxicity, and preliminary efficacy of ADI-PEG 20 combined with first-line pemetrexed and cisplatin chemotherapy in patients with ASS1-deficient mesothelioma or non-squamous non-small cell lung cancer (NSCLC). Methods: Up to 47 good performance (ECOG 0-1) patients are being enrolled in a 3+3+3 phase 1 design using tumoral ASS1 loss as a selection biomarker. W...