A phase 2 study of ARQ 501 in combination with gemcitabine in adult patients with treatment naïve, unresectable pancreatic adenocarcinoma

15017 Background: ARQ 501 is a DNA damage checkpoint pathway activator whose effect is to induce selective cell death in cancer cells, independent of the tumor cell’s p53 status. Current evidence implicates a rapid and sustained increase of the pro-apoptotic protein E2F-1 by ARQ 501 as the mechanism of action. Cancer cells are selectively affected due to their pre-existing DNA damage. Induction of E2F-1 in combination with gemcitabine demonstrated potent anti-tumor activity in xenografts of human pancreatic cancer (PACA-2). A recommended phase 2 dose of 400 mg/m 2 of ARQ 501 and 800 mg/m 2 gemcitabine was identified. Methods: A Phase 2 study in adult patients with treatment naïve, non-resectable adenocarcinoma of the pancreas was initiated to assess the effect of ARQ 501 and gemcitabine on ORR in approximately 66 patients. Cycles consisting of weekly ARQ 501 (400mg/m 2 ) and gemcitabine (800 mg/m 2 were repeated every 4 weeks until progression, unacceptable toxicity, or another discontinuation criterion was met. Results: 73 patients were enrolled, with 58 treated to date with at least one infusion. Data is available for 27 patients (16M/11F, median age, 63 years). Of these 27, 5 did not reach a post baseline assessment (3 deaths, 2 PD prior to week 8), 20 are evaluable for response at eight weeks (1 PR, 12 SD of 8–24+ weeks), 7 PD) and 2 have yet to be assessed but are active. Tumor regressions have been observed in 6/20 patients assessed to date. This includes 1 PR, 4 MR (14.3% - 24%) and 1 patient with significant reduction (29.6%) in pancreatic lesions although new superficial liver lesions were observed. Adverse events (N=235) the most common being: anemia (54, 22%), hemolysis (17, 7%), fatigue (15, 6%), edema (7, 3%), and nausea (5, 2%). Conclusions: ARQ 501 has been administered to 58 patients with treatment-naïve, non-resectable adenocarcinoma of the pancreas. Enrollment is complete and early efficacy data is encouraging. A high proportion of patients (13/20) have achieved a minimum SD at the first tumor evaluation. In addition, objective tumor regressions has been observed in this study, providing preliminary confirmation of the utility of induction of E2F-1 in combination with gemcitabine. [Table: see text]