Abstract OT1-08-02: TRYbeCA-2: A randomized phase 2/3 study of eryaspase in combination with gemcitabine and carboplatin chemotherapy versus chemotherapy alone as first-line treatment in patients with metastatic or locally recurrent triple-negative breast cancer (NCT03674242)
Authors: Awada Ahmad , Cortes Javier , Slater Sarah , MacPherson Iain , Csoszi Tibor , Bertrand Jean-Baptiste , Clermont Anne-Sophie , Pollard Rachel , Chrestia-Blanchine Romain , Biswas-Baldwin Nigel , Youssoufian Hagop , El-Hariry Iman 
Published: March 2020

Abstract
Background: Triple Negative Breast Cancer (TNBC) represents approximately 15% of all breast cancer. It confers a poorer prognosis relative to the other breast cancer subtypes, with an increased likelihood of recurrence and death within 5 years of diagnosis. There is no standard of care specifically for patients presenting with TNBC.
Altered amino acid metabolism have been shown to play a role in TNBC. 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. In a recent randomized Phase 2b study, eryaspase has demonstrated evidence of improved overall survival (OS) and progression free survival (PFS) and acceptable safety when combined with gemcitabine or FOLFOX therapy in patients with advanced pancreatic cancer whose disease progressed following first-line treatment (NCT02195180). The demonstration of ASNase activity of eryaspase in combination with chemotherapy including DNA-damaging agents in both preclinical and clinical settings provide a rationale to further test combination in TNBC.
Methods: TRYbeCA-2 is an international, randomized, open-label Phase 2/3 trial (N=64 for Phase 2) of eryaspase combined with chemotherapy in patients with locally recurrent or metastatic TNBC who have not received prior systemic therapy for locally recurrent or metastatic disease. Patients are randomized in a 1:1 ratio to receive gemcitabine/carboplatin with or without eryaspase, administered as IV infusion on Day 1 and Day 8 of each 3-week cycle.
Key eligibility criteria include measurable lesion(s), performance status 0 or 1, and adequate organ function. The primary endpoint is the objective response rate (ORR) as determined by an independent radiological review. Key secondary endpoints include ORR as determined by the investigator’s assessment, clinical benefit rate, overall survival, progression-free survival, safety, biomarker research, pharmacokinetics and pharmacodynamics.
A steering committee will be established to review safety at regular intervals and to review safety and efficacy data at the end of the Phase 2 to determine whether or not to proceed to Phase 3. The study is planned in European countries. Several sites have already been initiated and at least one patient was enrolled at the time of submitting this abstract.
Citation Format: Ahmad Awada, Javier Cortes, Sarah Slater, Iain MacPherson, Tibor Csoszi, Jean-Baptiste Bertrand, Anne-Sophie Clermont, Rachel Pollard, Romain Chrestia-Blanchine, Nigel Biswas-Baldwin, Hagop Youssoufian, Iman El-Hariry. TRYbeCA-2: A randomized phase 2/3 study of eryaspase in combination with gemcitabine and carboplatin chemotherapy versus chemotherapy alone as first-line treatment in patients with metastatic or locally recurrent triple-negative breast cancer (NCT03674242) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-08-02.