L-asparaginase (L-ASP) hydrolyses asparagine, an amino acid essential for the survival and proliferation of cancer cells. Asparagine synthetase (ASNS) expression is believed to play a role in determining sensitivity to asparaginase treatment. Eryaspase, L-ASP encapsulated in erythrocytes, showed encouraging activity and improved safety profile compared to L-ASP in patients (pts) with relapsed ALL. This prompted us to evaluate eryaspase in combination with chemo in pancreatic cancer (PC).
This open label, multicenter phase 2b randomized study (2:1) enrolled pts with second-line metastatic PC. Pts eligible to gemcitabine or FOLFOX regimen were randomized to chemo +/- eryaspase (100 IU/Kg D3 and D17 of 4-wk regimen) until disease progression. The endpoint of the study was improvement in PFS or OS in pts with no or low ASNS (0/1) expression as determined by IHC, with a target Hazard ratio (HR) < 0.85. Secondary endpoints included OS, PFS, ORR, safety and QoL. The primary analysis took place after around 6 mo follow-up (FUP).
140 pts were enrolled. The baseline characteristics were well balanced across the 2 treatment arms. The ASNS 0/1 (n = 65 and 32 in eryaspase & control arms, respectively), demonstrated a HR of 0.73 for PFS and 0.62 for OS; therefore the trial met its primary endpoint. In the entire patient population, eryaspase led to improvement of OS (median 26.1 wks) compared to control (median 19 wks); HR of 0.57 (P = 0.03). Similarly, eryaspase led to significant improvement in PFS. The treatment effect in favor of eryaspase was comparable across various prognostic indicators. Overall, treatment was well tolerated, with asthenia, nausea and vomiting, and myelosuppression being the most frequent events in both arms. Final results with additional FUP on efficacy and safety outcome measures will be provided at the meeting.
In pts with PC receiving second-line chemotherapy treatment, the addition of eryaspase provided significant improvement in OS and PFS, irrespective of ASNS expression levels. The role of the ASNS expression will be further investigated. Further investigation of eryaspase in PC in a P3 study is warranted.
Clinical trial identification
Legal entity responsible for the study
P. Hammel: Advisory board: Astra Zeneca; Merck Serono, Celgene, Shire, Ipsen. Corporate-sponsored research: Roche, Celgene. L. Mineur: Advisory board: Sanofi, Bayer and Roche. C. Louvet: Advisory board: Celgene and Roche. D. Tougeron: Advisory board: Sanofi, Amgen and Celgene. W. Berlier, A. Gupta: Employee pf Erytech Pharma. T. André: Advisory board: BMS, Amgen and Roche. I. El-Hariry: Employee as Chief Medical Officer, own stocks, Board of Directors: Erytech Pharma. All other authors have declared no conflicts of interest.