Eryaspase Demonstrates No Survival Benefit for Patients With Advanced PDAC: Phase 3 TRYBECA-1 Trial
Key Clinical Summary
- Population and Design: Phase 3 TRYBECA-1 trial evaluated eryaspase (100 U/kg IV, days 1 and 15 q4wk) plus chemotherapy vs chemotherapy alone in advanced PDAC after first-line progression (n = NR).
- Efficacy: Median OS 7.5 vs 6.7 mo (HR 0.92; 95% CI, 0.76–1.11; P = .374); PFS 3.7 vs 3.4 mo (HR 0.88; 95% CI, 0.73–1.07; P = .196); ORR 16.1% vs 12.5% (OR 1.35; 95% CI, 0.81–2.24)—no significant improvement with eryaspase.
- Safety: Grade ≥3 AEs were more frequent with eryaspase—neutropenia 25.4%, anemia 17.3%, asthenia 16.9%—but consistent with known chemotherapy profiles; results do not support further eryaspase development in PDAC.
The addition of eryaspase to standard chemotherapy did not improve survival outcomes among patients with advanced pancreatic ductal adenocarcinoma (PDAC) who progressed on first-line treatment, according to results from the phase 3 TRYBECA-1 trial published in the Journal of Clinical Oncology.
Researchers conducted a phase 3 clinical trial to evaluate the efficacy and safety of eryaspase combined with chemotherapy compared with chemotherapy alone as a second line treatment for patients with advanced PDAC. Chemotherapy regimens included gemcitabine/nab-paclitaxel or a fluoropyrimidine-based triplet (5-FU, leucovorin, and either irinotecan or nanoliposomal irinotecan). Eryaspase (100 U/kg IV) was administered on days 1 and 15 of each 4-week cycle.
The primary end point was overall survival (OS) and secondary end points included progression-free survival (PFS), objective response rate (ORR) and safety.
At the time of analysis, 420 deaths had occurred. The median overall survival (OS) was 7.5 months in the eryaspase group compared to 6.7 months in the chemotherapy alone group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.76 to 1.11; P = 0.374). The median PFS was 3.7 months in the eryaspase group compared to 3.4 months in the chemotherapy alone group (HR, 0.88; 95% CI, 0.73–1.07; P = 0.196), and the objective response rate (ORR) was 16.1% vs. 12.5% (odds ratio [OR], 1.35; 95% CI, 0.81 to 2.24), respectively.
In terms of safety, grade ≥ 3 adverse events were more frequent among the eryaspase group than the chemotherapy along group, including higher rates of neutropenia (25.4% vs. 20.3%), asthenia (16.9% vs. 13.8%), and anemia (17.3% vs. 12.2%).
The researchers concluded, “The addition of eryaspase to chemotherapy did not improve OS, PFS, or ORR. AEs were generally consistent with previous reports of chemotherapy.”
They added, “These results do not support additional development of eryaspase in PDAC.”
Source:
Hammel P, Metges JP, Macarulla Mercade T, et al. TRYBECA-1: A Randomized Phase III Study of Eryaspase Combined With Chemotherapy Versus Chemotherapy as Second-Line Treatment in Patients With Advanced Pancreatic Adenocarcinoma. Journal of Clinical Oncology. Published online November 4, 2025. doi:https://doi.org/10.1200/jco-25-00872
