Phase 1:The primary objective of the dose escalation portion of this study was to assess the safety and tolerability of ADI-PEG 20 in combination with folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin (mFOLFOX6) in advanced GI malignancies. The primary objective of the maximum tolerated dose (MTD) expansion phase (recommended phase 2 dose [RP2D]) of this study was to determine preliminary estimates of efficacy, measured by RECIST 1.1 criteria, for ADI-PEG 20 in combination with FOLFOX in hepatocellular carcinoma (HCC), gastro-esophageal cancer (GEC), and colorectal cancer (CRC).~Phase 2: The primary objective of this single arm trial is ORR. Based on a two-sided exact test of a one-sample proportion with an alpha of 0.05, under a presumed ORR of 22%, there is 80% power to yield 95% confidence interval of 15-26%, which will require 46 objective responses in 225 subjects. A futility analysis will be described in the Statistical Analysis Plan.
Phase 1: Assessment of safety and tolerability of ADI-PEG 20 in combination with folinic acid (leucovorin), fluorouracil and oxaliplatin (FOLFOX) in advanced GI malignancies.~Phase 2: Assessment of the objective response rate (ORR), measured by RECIST 1.1 criteria as assessed by blinded independent central review (BICR).