TRYBECA-1: A Randomized Phase III Study of Eryaspase Combined With Chemotherapy Versus Chemotherapy as Second-Line Treatment in Patients With Advanced Pancreatic Adenocarcinoma

Abstract

PURPOSE This phase III (ClinicalTrials.gov identifier: NCT03665441 ) study evaluated eryaspase in combination with chemotherapy as second-line treatment in advanced pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS TRYBECA-1 enrolled patients 18 years and older whose disease progressed on or after 1L chemotherapy. Patients were randomly assigned to eryaspase plus chemotherapy (gemcitabine/nab-paclitaxel or fluorouracil [5-FU], leucovorin [LV], and irinotecan/nanoliposomal irinotecan) or chemotherapy. Treatment was administered in a 4-week cycle for each of the following drugs until disease progression or unacceptable toxicity: eryaspase 100 U/kg intravenously on days 1 and 15; gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 intravenously on days 1, 8 and 15; irinotecan 180 mg/m 2 (or nanoliposomal irinotecan 70 mg/m 2 ) intravenously on days 1 and 15; 5-FU 2,400 mg/m 2 as one 46-hour infusion (with a bolus of 400 mg/m 2 ); and LV 400 mg/m 2 intravenously on days 1 and 15. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. RESULTS A total of 512 patients were randomly assigned (n = 255 for eryaspase and n = 257 for chemotherapy alone). Baseline characteristics were balanced between the two groups. There were 420 deaths, with a median OS of 7.5 months for eryaspase and chemotherapy versus 6.7 months for chemotherapy (hazard ratio [HR], 0.92 [95% CI, 0.76 to 1.11]; P = .374); the median PFS was 3.7 months versus 3.4 months (HR, 0.88 [95% CI, 0.73 to 1.07]; P = .196), and the ORR was 16.1% versus 12.5% (odds ratio, 1.35; [95% CI, 0.81 to 2.24]), respectively. Grade ≥3 adverse events (AEs) included neutropenia (25.4% v 20.3%), asthenia (16.9% v 13.8%), and anemia (17.3% v 12.2%) in the experimental versus control arms, respectively. CONCLUSION The addition of eryaspase to chemotherapy did not improve OS, PFS, or ORR. AEs were generally consistent with previous reports of chemotherapy. These results do not support additional development of eryaspase in PDAC.