Early data with a novel investigational agent have shown positive results in patients with metastatic pancreatic cancer, which has a dismal prognosis.
The product is L-asparaginase encapsulated in red blood cells and is known as eryaspase (Graspa, Erytech Pharma).
L-asparaginase is already used in the treatment of acute lymphoblastic leukemia, but toxicity has limited its use in solid tumors; the manufacturer says that encapsulating the product in red blood cells by using its proprietary technology makes the drug less toxic.
The new results in pancreatic cancer come from a phase 2 trial in 140 patients with metastatic disease being treated with standard of care (gemcitabine or the chemotherapy combination of fluorouracil, leucovorin, and oxaliplatin [FOLFOX]) and randomly assigned to also receive eryaspase or not. Patients received six cycles of treatment over a period of 4 weeks.
Top-line results released by the manufacturer show that eryaspase, used in combination with chemotherapy in the second-line setting, reduced the risk for death by 43%.
The median overall survival (OS) for patients receiving eryaspase was 26.1 weeks compared with 19 weeks for patients receiving the standard of care.
"These results generated by eryaspase in combination with the standard of care are highly encouraging and compare favorably to gemcitabine or FOLFOX treatment administered alone," commented principal investigator, Pascal Hammel, MD, PhD, gastroenterologist-oncologist at Beaujon Hospital in Paris, France, in a statement.
Asparagine synthetase (ASNS) expression status is believed to play a role in determining sensitivity to asparaginase treatment in several tumor types, including leukemia, lymphoma, and pancreatic cancer. In the current study, the primary objective was to evaluate the effect of eryaspase on both progression-free survival (PFS) and OS in patients with low ASNS, with a prespecified hazard ratio (HR) below 0.85 for either endpoint.
About 70% of the cohort had low ASNS (0/1), and in this prespecified result was met, showing an HR of 0.73 for PFS and 0.62 for OS.
However, the study authors found that eryaspase was effective regardless of ASNS expression. For the entire cohort, an HR of 0.57 was achieved for OS (P = .034).
Similar results were observed for PFS.
While ASNS expression does not appear to be predictive based on these results, it does seem to be predictive based on other studies, and so its role will be further explored in future clinical studies, according to the manufacturer.
The full results will be presented at an upcoming medical conference, and discussions will also be initiated with regulatory agencies, the company said. "We have been studying the metabolic pathways for the past decade with the aim to develop effective treatments for patients with metabolically-driven tumors," commented Gil Beyen, chairman and CEO of Erytech in a statement.
"We are very excited by these new positive data," he continued. "They provide further important clinical proof of concept supporting the development of eryaspase as a potential treatment in one of the most aggressive tumor types."