Abstract B22: Trybeca-1: A randomized, phase 3 study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441)
Authors: Hammel Pascal , Berardi Rosanna , Cutsem Eric Van , Feliu Jaime , Greil Richard , Wasan Harpreet , Metges Jean-Philippe , Nygren Peter , Österlund Pia , Noel Marcus , Seufferlein Thomas , Creemers Geert-Jan , Gupta Anu , Salesse Sophie , Biswas-Baldwin Nigel , Dion Hedy , Youssoufian Hagop , El-Hariry Iman , Hidalgo Manuel 
Published: March 2020

Abstract
Background: Second-line treatment options for advanced pancreatic adenocarcinoma are currently limited. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs), is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. We have recently reported the outcome of a randomized phase 2b study in patients with advanced pancreatic cancer whose disease progressed following first-line treatment (NCT02195180). Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression-free survival (PFS). The safety profile of eryaspase was acceptable. The results of this phase 2b study provided a rationale for initiating this confirmatory phase 3 pivotal trial (TRYbeCA-1).
Methods: TRYbeCA-1 is an international, randomized, open-label phase 3 trial (N= ~500) of eryaspase combined with chemotherapy in patients with adenocarcinoma of the pancreas who have failed only one prior line of systemic anticancer therapy for advanced pancreatic cancer and have measurable disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or irinotecan liposome injection/5-fluorouracil/leucovorin) with or without eryaspase, administered as IV infusion on Day 1 and Day 15 of each 4-week cycle. Key eligibility criteria include performance status 0 or 1, stage IV disease, documented evidence of disease progression, available tumor tissue, and adequate organ function. The primary endpoint is OS. Key secondary endpoints include PFS and objective response rate, safety, quality of life, pharmacokinetics and pharmacodynamics, and biomarker research. A hazard ratio in OS of 0.725 is being targeted, which represents a conservative estimate based on the phase 2b data and is viewed as being highly clinically relevant. An IDMC will be established to review safety at regular intervals and to review efficacy data at the planned interim and final analyses.
Citation Format: Pascal Hammel, Rosanna Berardi, Eric Van Cutsem, Jaime Feliu, Richard Greil, Harpreet Wasan, Jean-Philippe Metges, Peter Nygren, Pia Österlund, Marcus Noel, Thomas Seufferlein, Geert-Jan Creemers, Anu Gupta, Sophie Salesse, Nigel Biswas-Baldwin, Hedy Dion, Hagop Youssoufian, Iman El-Hariry, Manuel Hidalgo. Trybeca-1: A randomized, phase 3 study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with pancreatic adenocarcinoma (NCT03665441) [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B22.