Clinical Trials

Date: 2017-09-08

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the European Society for Medical Oncology (ESMO) 2017 Congress

Company: Erytech Pharma (France)

Product: Ery-asp®/Graspa® (eryaspase - L-asparaginase loaded erythrocytes)

Action mechanism:

• enzyme. Eryasp® (eryaspase) is a  L-asparaginase encapsulated in red blood cells, with a safer and broader range of clinical use than existing forms due to the entrapment and protection of the enzyme inside red blood cells.

Disease: pancreatic cancer

Therapeutic area: Cancer - Oncology

Country: France

Trial details:

• The ERY-ASP pancreatic cancer Phase II study is a multicenter, randomized trial for the second-line treatment of patients with progressive metastatic pancreatic cancer. In a study of approximately 90 patients, conducted in France, ERY-ASP in addition to the standard of care (Gemcitabine or Folfox) is being compared to the standard of care alone in a 2-to-1 randomization. Approximately 90% of patients received gemcitabine. Baseline characteristics and patient demographics were similar between the two treatment groups.
• The primary endpoint is progression-free survival (PFS) at 4 months. The primary endpoint will be progression free survival (PFS) at 4 months. Patients will be stratified according to the expression of asparaginase synthetase  of their primary tumor. Low expression of ASNS is believed to be an indicator of tumor sensitivity to asparaginase. (NCT02195180)

Latest news:

• • On September 8, 2017, Erytech Pharma announced the presentation of the full data from its Phase 2b study evaluating eryaspase (Graspa®) in combination with chemotherapy for the treatment of metastatic pancreatic cancer. The study met its co-primary endpoints and demonstrated significant improvement in both overall survival (OS) and progression-free survival (PFS). The results have been presented during the European Society for Medical Oncology (ESMO) Annual Meeting.
• The study evaluated eryaspase as a second-line treatment in combination with chemotherapy in 141 patients suffering from metastatic pancreatic cancer. It met its co-primary endpoints of OS and PFS with Hazard Ratios (HR) below 0.85 in patients with no or low asparagine synthetase expression (ASNS 0/1), approximately 70% of the study population, and demonstrated statistically significant improvements of OS and PFS in the entire patient population. The associated sensitivity analyses and subgroup evaluations indicate the consistent treatment benefit with eryaspase across the treated populations.
• Highlights of the study results include:
• – Co-primary endpoints met: HR of 0.65 for OS and 0.72 for PFS in the ASNS 0/1 patient population
• – Statistically significant improvement of OS and PFS in the entire patient population:
• ¤ HR of 0.60 for OS (95% CI; 0.40, 0.88) (p=0.009)
• median OS of 26.1 weeks (95% CI; 21.0, 28.4) in the eryaspase arm vs. 19.0 weeks (95% CI; 12.3, 26.3) in the standard of care arm
• one-year survival of 14.8% vs. 3.0%, respectively
• ¤ HR of 0.59 for PFS (95% CI; 0.40, 0.89) (p=0.011)
• median PFS of 8.6 weeks (95% CI; 7.6, 14.6) in the eryaspase arm vs. 7.0 weeks (95% CI; 6.1, 7.6) in the standard of care arm
• 16.9% of patients without disease progression at 24 weeks vs. 5.8%, respectively
• ¤ Improved objective response rate (ORR) and disease control rate (DCR) in the entire patient population:
• ORR of 11.6% in the eryaspase arm vs. 6.5% in the standard of care arm
• DCR of 47.4% in the eryaspase arm vs. 23.9% in the standard of care arm
• ¤ Patients with high ASNS-expressing tumors (ASNS2/3) had a worse prognosis, but also a better relative treatment benefit:
• HR of 0.45 for OS and 0.38 for PFS
• DCR of 51.7% in the eryaspase arm vs. 7.1% in the standard of care arm
• ¤ The toxicity profile was similar in the two treatment arms:
• The percentage of patients with at least one Grade 3 or 4 adverse event (AE) was 77% in the eryaspase-treated arm compared to 86% in the control arm. The most common Grade 3 or 4 AEs were: increased gamma-glutamyl transferase (17% vs. 25%), neutropenia (13% vs. 11%), general health deterioration (13% vs. 2%), and thrombocytopenia (10% vs. 7%), respectively.
• The percentage of patients with at least one serious adverse events (SAE) was 45% in the eryaspase-treated arm compared to 50% in the control arm. The most common SAEs were: general health deterioration (9% each), gastro-intestinal hemorrhage (2% vs. 7%, respectively).
• • On September 26, 2016, Erytech Pharma announced the final patient has been enrolled in its Phase 2 trial of eryaspase for the treatment of pancreatic cancer.  The trial has completed enrollment of 139 patients and the company expects to report primary results from this trial by early 2017.
• • On July 20, 2015, Erytech Pharma announced a positive DSMB safety review following the treatment of the first twenty-four patients with eryaspase  in its Phase 2 study in pancreatic cancer. The DSMB raised no safety concerns, and recommended the continuation of enrollment in the study. Two earlier DSMB reviews recommended proceeding with the combination of eryaspase  with gemcitabine and FOLFOX after safety evaluation of the first three patients in each treatment regimen.
• • On June 22, 2015, Erytech Pharma announced positive safety reviews following the treatment of the first three patients with eryaspase  in combination with Folfox in its Phase II study in pancreatic cancer.
• • On July 28, 2014, Erytech Pharma announced the enrollment of the first patient in its Phase II study with eryaspase  in second line treatment of patients affected by pancreatic cancer. Three months after its authorization by the ANSM, the French authority for drug safety, a first patient has been enrolled. In a study of about 90 patients, ERY-ASP in addition to the standard of care will be compared to the standard of care alone in a 2-to-1 randomization. The primary endpoint will be progression-free survival (PFS) at 4 months.
• • On May 6, 2014, Erytech Pharma has announced that the ANSM, French healthcare agency, has granted the authorization to start a Phase II study in second line treatment of patients affected by pancreatic cancer. The company has already successfully completed a Phase I study in late stage pancreas cancer, in which the tolerability of ERY-ASP has been confirmed in this very fragile patient population. Erytech has decided to continue the development in solid tumors by performing a Phase II study in second-line therapy for patients with progressive metastatic pancreas cancer. Scientific advice had been obtained at the end of last year from the European Medicines Agency (EMA) and a clinical trial application (CTA) was subsequently submitted to the ANSM (Agence Nationale de Sécurité du Médicament, the French healthcare agency), who now gave its green light for the study. Patient enrollment is expected to start in Q2 2014. Professor Pascal Hammel, gastroenterologist specialized in digestive oncology at Hôpital Beaujon (Clichy-Paris, France), is the principal investigator of the study.
• * On January 7, 2014,  Erytech Pharma has provided an update on its development plans to broaden the scope of Eryasp® into the large field of solid tumors and has announced the launch of a Phase II study in pancreatic cancer. After having performed multiple clinical studies in acute leukemia, the research and development teams of Erytech Pharma have, in collaboration with researchers at the world renowned MD Anderson Cancer Center in Houston, worked at confirming the mode of action and the potential of Eryasp® in other cancer indications. In extensive testing on a large number of tumor samples, it was found and published in a high ranking peer reviewed journal2 that 50% to 90% of known solid tumors are eligible for treatment through the concept of tumor starvation by administration of asparaginase.

Is general: Yes