Although the addition of eryaspase to chemotherapy improved overall survival over chemotherapy alone in patients with metastatic pancreatic cancer, the difference in benefit was not found to be statistically significant, missing the primary end point of the phase 3 TRYbeCA-1 trial.
Although the addition of eryaspase to chemotherapy improved overall survival (OS) over chemotherapy alone in patients with metastatic pancreatic cancer, the difference in benefit was not found to be statistically significant, missing the primary end point of the phase 3 TRYbeCA-1 trial (NCT03665441).1
Top-line data demonstrated that the median OS in the intent-to-treat population was 7.5 months (95% CI, 6.5-8.3) with eryaspase and chemotherapy vs 6.7 months (95% CI, 5.4-7.5) with chemotherapy alone (HR, 0.92; 95% CI, 0.76-1.11; P = .375).
Notably, the addition of eryaspase to gemcitabine and nab-paclitaxel (Abraxane) did not produce a survival benefit in this population, but when the agent was added to an irinotecan-based chemotherapy regimen, a nominal benefit was reported compared with chemotherapy alone (HR, 0.77; 95% CI, 5.7-1.05). The median OS in this prespecified subset was 8.0 months with the eryaspase combination vs 7.5 months with the control regimen.
Moreover, findings regarding progression-free survival (PFS), disease control rate (DCR), and objective response rate (ORR) were all found to be in favor of the addition of eryaspase to chemotherapy vs chemotherapy alone. The toxicity of the agent proved to be consistent with prior findings.
“While the results are disappointing, we congratulate the company for a very well managed trial in this difficult disease,” Pascal Hammel, MD, PhD, professor and gastroenterologist oncologist at Beaujon Hospital and co-principal of TRYbeCA-1, stated in a press release. “With a median survival of 7.5 months, Erytech has created a new reference standard for clinical evaluation in second-line pancreatic cancer.”
In prior studies, eryaspase has been found to have acceptable tolerability and to be an effective chemotherapy partner in patients with acute lymphoblastic leukemia and pancreatic adenocarcinoma.2 Results from a previous phase 2 trial (NCT02195180) showed that the addition of the agent to chemotherapy resulted in a clinically meaningful improvement in OS in patients with advanced pancreatic adenocarcinoma whose disease progressed after frontline treatment, resulting in a 40% reduction in the risk of death vs the control (HR, 0.60; P = .008).
These data provided the rationale to launch the confirmatory phase 3 TRYbeCA-1 trial, which set out to enroll approximately 500 patients with stage III or IV pancreatic cancer who received 1 prior therapy in the advanced setting and who had an ECOG performance status of 0 or 1.
To be eligible for enrollment, patients needed to be at least 18 years of age, have histologically confirmed pancreatic adenocarcinoma, acceptable organ function, and a life expectancy of more than 12 weeks. Notably, those with brain metastases were permitted, if they were stable.
On the trial, patients who had received frontline gemcitabine-based chemotherapy were randomized 1:1 to receive second-line FOLFIRI or NALIRI with or without eryaspase. Those who received first-line fluoropyrimidine-based chemotherapy were randomized 1:1 to receive gemcitabine or abraxane with or without eryaspase.
Intravenous eryaspase was given every 2 weeks at a dose of 100 U/kg on day 1 and 15 of each 4-week cycle; this was followed by chemotherapy. Gemcitabine was given at a dose of 1000 mg/m2 and nab-paclitaxel was given at a dose of 125 mg/m2 on days 1, 8, and 15 of each 4-week cycle.
Irinotecan was given at 70 mg/m2, 5-fluorouracil at 2400 mg/m2 over 46 hours, and leucovorin at 400 mg/m2 on days 1 and 15 of each 4-week cycle, or patients received irinotecan at 180 mg/m2, 5-FU at 400 mg/m2 bolus followed by 2400 mg/m2 infusion over 46 hours, and leucovorin at 400 mg/m2 on days 1 and 15 of every 4-week cycle.
Treatment was administered until progressive disease or intolerable toxicity.
Stratification factors included performance status, choice of chemotherapy, and time since diagnosis of advanced disease.
The primary objective of the research was OS, and key secondary objectives were PFS, ORR, duration of response, and DCR. Investigators also set out to examine safety and tolerability, quality of life, pharmacokinetics and pharmacodynamics, immunogenicity, and biomarkers.
“Pancreatic cancer is a very challenging, heterogenous disease, and the results of the TRYbeCA-1 phase 3 trial have now also encountered this significant hurdle,” Iman El-Hariry, MD, PhD, chief medical officer of Erytech, stated in a press release. “It is very disappointing that the clinical benefit of eryaspase demonstrated in the phase 2 trial was not confirmed; however, the study has addressed important questions in the management of [patients with] pancreatic cancer.”
Manuel Hidalgo, MD, PhD, of Weill Cornell Medicine/NewYork-Presbyterian Hospital and co-principal investigator of TRYbeCA-1, added that the results observed in the subgroup of patients who received fluoropyrimidine-based treatment warrant further investigation.
Erytech Pharma, the developer of eryaspase, shared that further analysis of the findings will be done and full findings will be shared at an upcoming medical meeting.