Topline results show that the addition of eryaspase to chemotherapy does not prolong survival in the general advanced pancreatic cancer population, but there may be benefit for those treated with irinotecan.
Second-line treatment with erythrocyte-encapsulated asparaginase (eryaspase) combined with chemotherapy did not prolong overall survival (OS) compared with chemotherapy alone in patients with advanced pancreatic cancer, missing the primary end point of the phase 3 TRYbeCA-1 clinical trial, according to topline results announced in a press release by ERTECH Pharma.1
Despite being negative for the primary end point, the irinotecan and eryaspase treated subgroup in the TRYbeCA-1 had a trend toward survival benefit, meeting a key secondary end point.
“…The results in the subgroup of fluoropyrimidine-based treatments are, with a median survival of 8 months, really remarkable and merit further investigation. Especially since this was also the better subgroup in the phase 2b trial, said Manuel Hidalgo Medina, MD, PhD, chief of the Division of Hematology and Medical Oncology at Weill Cornell Medicine/NewYork-Presbyterian Hospital, and co-investigator of TRYbeCA-1, in a press release.
In TRYbeCA-1, 500 patients were enrolled and randomly assigned 1:1 to receive eryaspase in combination with a gemcitabine- or irinotecan-based chemotherapy combination in the experimental arm or chemotherapy alone in the control arm. Eryaspase was administered at 100 U/kg every 2 weeks. Gemcitabine was dosed at 1000 mg/m2 combination with paclitaxel 125 mg/m2 as another chemotherapy combination option. Patients could also receive the FOLFIRI regimen with irinotecan 70 mg/m2 plus fluorouracil (5-FU) 2400 mg/m2 plus leucovorin 400 mg/m2 or FOLFIRI with a higher dose of irinotecan (180 mg/m2).2
In addition to OS, progression-free survival, objective response rate, duration of response, disease control rate, the incidence of treatment-related adverse events, and quality of life were investigated as secondary end points.
The median OS observed with eryaspase plus chemotherapy in the intent-to-treat population was 8.0 months versus 5.7 months in the chemotherapy-only arm (HR, 0.77; 95% CI, 5.5-1.05). The result was nominal, according to ERTECH Pharma. In terms of safety, the profile of eryaspase was consistent with prior reports provided by the independent data monitoring committee.
“While the results are disappointing, we congratulate the company for a very well-managed trial in this difficult disease. With a median survival of 7.5 months, ERYTECH has created a new reference standard for clinical evaluation in second-line pancreatic cancer,” said Pascal Hammel, Md, PhD, professor, and gastroenterologist-oncologist at Beaujon Hospital in Paris and co-principal investigator of the study, in the press release.1
Patients eligible to be included in the study were those aged 18 years or older with histologically confirmed stage III or IV pancreatic adenocarcinoma. Patients were required to have received at least 1 prior line of systemic chemotherapy in the advanced setting. All patients must have also had radiographic evidence of disease progression, ECOG performance status of 0 or Karnofsky Performance Status ≥ 80, a life expectancy of at least 12 weeks, tissue for biopsy, and adequate laboratory test results at baseline.2
“Pancreatic cancer is a very challenging, heterogeneous disease, and the results of the TRYbeCA-1 phase 3 trial have now also encountered this significant hurdle.” said Iman El Hariry, MD, PhD, chief medical officer of ERYTECH, in a press release. “It is very disappointing that the clinical benefit eryaspase demonstrated in the phase 2 trial was not confirmed; however, the study has addressed important questions in the management of pancreatic cancer patients.1”
1. ERYTECH announces results from TRYbeCA-1 phase 3 trial of eryaspase in patients with second-line advanced pancreatic cancer. News release. October 25, 2021. Accessed October 25, 2021. https://bit.ly/3beFrL6
2. Study of eryaspase in combination with chemotherapy versus chemotherapy alone as 2nd-line treatment in PAC (Trybeca-1). Clinicaltrials.gov. Accessed October 25, 2021. https://bit.ly/3bgkS0R