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Asparagine

eryaspase 100 U/kg dosed every 2 weeks in combination with

Gemcitabine plus abraxane (albumin-bound paclitaxel) administered on Days 1, 8, and 15 of each 4 week cycle as follows:

* Abraxane (125 mg/m2) IV
* Gemcitabine (1000 mg/m2) IV

Or

Irinotecan plus 5-FU plus leucovorin administered on Days 1 and 15 of each 4 week cycle as follows:

* Onivyde 70 mg/m2 (irinotecan freebase) IV (recommended dose in patients homozygous for UGT1A1\*28 is 50 mg/m2)
* Leucovorin 400 mg/m2 IV
* 5 FU 2400 mg/m2

Or

* FOLFIRI: Irinotecan 180 mg/m2 IV
* Leucovorin 400 mg/m² IV
* 5 FU 400 mg/m² IV bolus
* 5 FU 2400 mg/m² IV continuous infusion over 46 hours immediately following bolus 5 FU

Standard treatment: Gemcitabine plus abraxane (albumin-bound paclitaxel) administered on Days 1, 8, and 15 of each 4 week cycle Or Irinotecan plus 5-FU plus leucovorin administered on Days 1 and 15 of each 4 week cycle

L-asparaginase encapsulated in erythrocytes (red blood cells)

eryaspase

Gemcitabine plus Abraxane

Irinotecan plus 5-FU plus leucovorin

Manuel Hidalgo, MD, PhD

Pascal Hammel, MD, PhD

This is an open-label, multicenter, randomized, Phase 3 study in patients with ductal adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease.

Patients who meet all inclusion and exclusion criteria will be randomized in a 1:1 ratio to one of the following treatment arms (see figure below):

* Arm A (investigational arm): eryaspase in combination with either gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI \[FOLinic acid-Fluorouracil-IRInotecan regimen\] or Onivyde®/5 fluorouracil/leucovorin), or
* Arm B (control arm): gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI or Onivyde/5-FU/leucovorin)

The chemotherapy will be investigator's choice and based on what patient has received in first line treatment. Treatment will continue until disease progression, unacceptable toxicity, or the patient's withdrawal of consent.

An End of Treatment visit should occur within approximately 30 days from last dose of eryaspase or chemotherapy regimen.

A survival follow-up period will include the collection of survival, progression of disease if applicable, treatment updates, and quality of life assessments every 8 weeks.

Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment in PAC

A Randomized, Phase 3 Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment of Patients With Pancreatic Adenocarcinoma

To determine whether the addition of eryaspase to chemotherapy improves OS when compared to chemotherapy alone

To compare PFS between the 2 treatment arm. Progression is determined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

To compare the ORR between the 2 treatment arms. ORR is defined as the proportion of patients who achieve objective tumor response (CR or PR) per modified RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.

To compare the DoR between the 2 treatment arms

To compare the between the 2 treatment arms

To evaluate the safety and tolerability of eryaspase in combination with chemotherapy versus chemotherapy alone by assessing the number of patients with with treatment emergent adverse events per CTCAE v5.0

The time to first Worsening was defined as the date of randomization to the date of first Worsening occurred in patient score on their global health status. Patients who did not have any worsening were censored at date of last measurement or at baseline if no measurement is available post-baseline.

ERYtech Pharma

eryaspase 100 U/kg dosed every 2 weeks in combination with

Gemcitabine plus abraxane (albumin-bound paclitaxel) administered on Days 1, 8, and 15 of each 4 week cycle as follows:

* Abraxane (125 mg/m2) IV
* Gemcitabine (1000 mg/m2) IV

Or

Irinotecan plus 5-FU plus leucovorin administered on Days 1 and 15 of each 4 week cycle as follows:

* Onivyde 70 mg/m2 (irinotecan freebase) IV (recommended dose in patients homozygous for UGT1A1\*28 is 50 mg/m2)
* Leucovorin 400 mg/m2 IV
* 5 FU 2400 mg/m2

Or

* FOLFIRI: Irinotecan 180 mg/m2 IV
* Leucovorin 400 mg/m² IV
* 5 FU 400 mg/m² IV bolus
* 5 FU 2400 mg/m² IV continuous infusion over 46 hours immediately following bolus 5 FU

eryaspase: L-asparaginase encapsulated in erythrocytes (red blood cells)

Gemcitabine plus Abraxane: gemcitabine, Abraxane

Irinotecan plus 5-FU plus leucovorin: irinotecan, 5-FU, leucovorin

Eryaspase Plus Chemotherapy

Standard treatment: Gemcitabine plus abraxane (albumin-bound paclitaxel) administered on Days 1, 8, and 15 of each 4 week cycle Or Irinotecan plus 5-FU plus leucovorin administered on Days 1 and 15 of each 4 week cycle

Gemcitabine plus Abraxane: gemcitabine, Abraxane

Irinotecan plus 5-FU plus leucovorin: irinotecan, 5-FU, leucovorin

Chemotherapy Alone

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Europe

Region of Enrollment

ECOG 0

ECOG 1

ECOG Performance Status (PS) assesses patient's level of functioning Grade 0 to 4 in terms of their ability to care for themselves, daily activity, and physical ability:

Grade 0=Fully active, able to carry on all pre-disease performance without restriction; Grade 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.

Patients with Grades 2 to 5 were not included.

ECOG PS

<6 months

>=6 months

Time from initial diagnosis of advanced disease to randomization

Anu Gupta, Senior Study Team Lead

Overall Survival (OS)

Progression Free Survival (PFS)

Objective Response Rate (ORR)

Duration of Response (DoR)

Disease Control Rate (DCR)

Number of patients with treatment emergent adverse events (TEAE)

number of patients with TEAE >= Grade 3

Number of patients with TE SAE

Number of patients with TEAEs leading to study drug discontinuation

Number of patients with TE SAE with outcome of death

Analysis set includes only patients who were treated on study (Safety Population). 7 patients in the eryaspase plus chemotherapy arm and 11 patients in the chemotherapy alone arm discontinued study prior to initiation of first dose.

Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v5.0

The number of participants in this section consist of all patients who receive at least one dose of the study treatment and provide answers to at least some items of the EORTC QLQ-C30 at Cycle 1 Day 1 (i.e, baseline) and a time point after the date of first dose of study treatment.

Time to Quality of Life Questionnaire EORTC QLQ-C30 First Worsening in Global Health Status Analysis

Overall Study

Spots Global Cancer Trial Database for asparagine depletion