Patients treated with eryaspase for second line advanced pancreatic cancer did not meet the primary end point of overall survival in the TRYbeCA-1 trial.
Treatment with eryaspase plus chemotherapy in a population of patients with second-line advanced pancreatic cancer did not result in a significant improvement of overall survival (OS), according to a press release from the drugs developer ERYTECH on the phase 3 TRYbeCA-1 trial (NCT03665441). However, investigators noted that the regimen yielded superior disease control in the study.
Although the eryaspase regimen did demonstrate an improvement in OS compared with chemotherapy alone in the intent-to-treat population, it was notably not statistically significant (HR, 0.92; 95% CI, 0.76-1.11; P = .375). The median OS was 7.5 months (95% CI, 6.5-8.3) for patients treated with the eryaspase combination compared with 6.7 months (95% CI, 5.4-7.5) for patients treated with chemotherapy.
Despite not experiencing a survival benefit when eryaspase was added to gemcitabine plus nabpaclitaxel, patients who received eryaspase and an irinotecan-based chemotherapy regimen experienced a nominal survival benefit versus chemotherapy alone (HR, 0.77; 95% CI, 5.7-1.05). The cohort also had a median OS of 8.0 months compared with 5.7 months in the chemotherapy arm.
“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,” co-principal investigator Pascal Hammel, MD, PhD, a professor and gastroenterologist-oncologist at Beaujon Hospital in Paris, said in a press release.
Eryaspase is an L-asparaginase encapsulated inside donor-derived red blood cells, which target cancer cells capable of alter asparagine and glutamine metabolism.
The TRYbeCA-1 trial enrolled 512 patients with metastatic disease to receive treatment with second-line eryaspase every 2 weeks with a 100 U/kg dose. Patients in the trial were also given a chemotherapy backbone consisting of gemcitabine plus abraxane on days 1, 8, and 15 of each 4-week cycle. Alternatively, irinotecan plus 5-fluorouracil and leucovorin could be used as the chemotherapy backbone on days 1 and 15.
To be eligible for this trial, patients needed to have histologically confirmed stage III or IV pancreatic adenocarcinoma and have received 1 line of systemic chemotherapy in the advanced setting. Additionally, radiological evidence of disease progression following the most recent treatment was required.
Secondary end points for the study included progression-free survival, disease control rate, and objective response rate. All secondary end points highlighted a nominal clinical benefit among those treated with eryaspase.
Moving forward, ERYTECH will continue focusing on developing eryaspase for patients with acute lymphoblastic leukemia (ALL). Eryaspase was previously given fast track designation by the FDA in July of 2021 based off the results from the phase 2 NOR-GRASPALL-2016 trial (NCT03267030), which assessed the use of asparaginase encapsulated in erythrocytes in patients with Philadelphia chromosome–positive ALL with a hypersensitivity to pegylated asparaginase.
“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. 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,” Iman El Hariry, MD, chief medical officer at ERYTECH, concluded.
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 28, 2021. https://yhoo.it/2XTYSWF