A phase IIb of eryaspase in combination with gemcitabine or FOLFOX as second-line therapy in patients with metastatic pancreatic adenocarcinoma (NCT02195180).

Abstract

e15718 Background: L-asparaginase (L-ASP) hydrolyses asparagine (ASN) leading to depletion of this amino acid. While normal cells are protected from ASN requirement due to their ability to produce ASN,.leukemic lymphoblasts and most cancer cells have a very low level or even lack of L-asparagine synthetase (ASNS), and thus depend on serum ASN for their proliferation and survival. L-ASP depletes serum ASN, which in turn inhibits the protein synthesis, resulting in cell cycle arrest and apoptosis in susceptible cancer cells, especially pancreatic cancer cells Eryaspase, which is L-ASP encapsulated in red blood cells, recently showed an encouraging activity and improved safety profile compared to L-ASP in patients (pts) with relapsed ALL. Knowing that up to 70% of pancreatic adenocarcinomas (PC) have low or null ASNS expression (Bachet Pancreas 2015), prompted us to evaluate the efficacy and safety of eryaspase in combination with chemo in PC. Methods: This open label, multicenter phase II randomized study (2:1) enrolled pts with second-line metastatic PC. Pts eligible to gemcitabine or FOLFOX regimen (according to first line chemo) were randomized to chemo +/- eryaspase (100 IU/Kg D3 and D17 of 4-wk regimen) until disease progression Primary end point: progression free survival in pts with ASNS negative tumors (0/1+). ASNS expression was measured using immunohistochemistry and optical density. Key secondary endpoints: PFS in ASNS positive pts (2+/3+), overall survival, biomarkers ( KRASmutation, cell free DNA), and safety. Results: 141 pts were enrolled. Treatment was generally well tolerated, with no safety concerns based on IDMC reviews. ASNS expression was negative in 69%, and positive in 31% of the pts At the time of submission, PFS and OS analysis and the correlation of ASNS expression with clinical outcomes were not yet available but will be presented at the meeting. Conclusions: This is the largest set of PC pts tested for the expression of ASNS and treated in second line with an asparaginase combined with chemotherapy. The ASNS expression levels may be a potential therapeutic target and therefore predictive of response to eryaspase for the treatment of advanced PC. Clinical trial information: NCT02195180.