Phase Ib Trial Of Adi-Peg 20 (A) Plus Nab-Paclitaxel (Nab-P) And Gemcitabine (Gem) In Patients With Advanced Pancreatic Cancer (Pc)

295Background: ADI-PEG 20 (A) is a pegylated form of arginine depleting enzyme, arginine deaminase. Normal cells synthesise arginine using the enzyme argininosuccinate synthetase (ASS). A selectively targets malignant cells which lack ASS. A has shown encouraging pre clinical activity as monotherapy in PC, and synergistic activity with gem and taxanes. Methods: Eligibility: Metastatic PC, up to one line of prior treatment (dose escalation cohort:ct) no prior treatment (expansion ct), ECOG 0-1.Treatment: gem 1,000 mg/m2, nab-P 125mg/m2 3 out of 4 weeks, A 18 mg IM weekly (ct 1), A 36mg weekly (ct 2 and expansion ct). Primary endpoint: determine MTD of A in combination with nab-P and gem. Statistical plan: Single arm, non-randomized, open-label, phase IB, standard 3 + 3 dose escalation with expansion ct of 9 patients at MTD. Secondary endpoints: progression-free survival (PFS), response rate, overall survival (OS), safety, tolerability, blood and archival tumor analyses for ASS expression and immunogenicity...