Pancreatic cancer is a particularly aggressive type of cancer, with a five-year survival rate of less than 10%. It is also one of the fastest growing cancer indications. With approximately 185,000 new cases diagnosed each year in Europe and the United States annually, pancreatic cancer represents an important unmet medical need.
In 2017, we reported positive Phase 2b clinical trial data of eryaspase in combination with chemotherapy for the second-line treatment of patients with metastatic pancreatic cancer. The open-label, randomized, multi-center clinical trial in 141 patients met its co-primary endpoints and demonstrated significant improvement in both overall survival (OS) and progression-free survival (PFS). The hazard ratio for overall survival in the entire patient population was 0.60 (nominal p-value = 0.008), meaning that treatment with eryaspase reduced the risk of death rate by 40% compared to treatment with chemotherapy alone.
This clinical trial represents the first time an asparaginase-based therapy has been reported to have a survival benefit in a solid tumor indication. This trial formed the basis for our strategy to explore the further development of eryaspase for the treatment of pancreatic cancer and other solid tumor indications.
In 2018, we launched the Phase 3 TRYbeCA-1 trial which enrolled 512 second-line metastatic pancreatic cancer patients at approximately 90 clinical sites in 11 countries in Europe and the United States. In this trial, eligible patients were randomized 1-to-1 to receive eryaspase in combination with standard chemotherapy (gemcitabine/nab-paclitaxel or an irinotecan-based regimen) or chemotherapy alone.
Top-line results for the TRYbeCA-1 trial were released in October 2021. Though the study did not meet its primary endpoint of overall survival (OS) in the intent-to-treat population, a positive trend towards improved OS in patients who received eryaspase and irinotecan-based therapy (FOLFIRI) compared to irinotecan-based therapy alone was observed.
Final study results was presented at ASCO-GI in 2022.
Additional clinical experience for the combination of eryaspase and irinotecan-based chemotherapy in pancreatic cancer is being gained through an ongoing investigator sponsored Phase 1 trial evaluating eryaspase in combination with modified FOLFIRINOX as part of first-line treatment for locally advanced and metastatic pancreatic cancer. Sponsored by Georgetown University (Washington DC, US), rESPECT is a single-arm, open-label dose escalation Phase 1 trial which is expected to enroll approximately 18 patients. After the first two dose cohorts in the trial, the maximum tolerated dose of eryaspase in combination with mFOLFIRINOX has been determined at 100 U/kg with no dose limiting toxicities and initial encouraging signs of efficacy observed.