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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

Oxaliplatin

Folfirinox

Immunosuppressive Agents

Immunologic Factors

Eryaspase will be administered on day 1 and 15 of a 4 week cycle (intravenous infusion) in dose escalating/reduction depending on the cohort the patient is assigned to

mFOLFIRINOX dosing will include 5-fluorouracil 2400 mg/m² over 46 hours, oxaliplatin 85 mg/m², Irinotecan 150 mg/m² (intravenous infusion) on Day 1 and 15 of the 4 weeks cycle for a maximum of 12 cycles.

intravenous administration of Eryaspase, starting dose 75 units/kg, dose escalation to 100 units/kg, dose reduction 50 units/kg and 25 units/kg

FOLFIRINOX

Marcus S Noel, MD

This will be a single-arm, multi-center, open-label phase 1 study. The standard 3+3 design will be used to determine the maximum tolerated dose (MTD) from 4 possible dose levels of Eryaspase in combination with mFOLFIRINOX. We hypothesize that the addition of Eryaspase to FOLFIRINOX (5-fluorouracil \[5-FU\], leucovorin, irinotecan, and oxaliplatin) will be safe and demonstrate preliminary signs of efficacy in patients with advanced pancreatic cancer. Safety assessments include adverse events, physical examination abnormalities, vital signs, and clinical laboratory tests (including blood chemistry, hematology, and coagulation panel).

This is an open-label, multicenter, Phase 1 study of Eryaspase combination with FOLFIRINOX in patients with locally advanced or metastatic pancreatic adenocarcinoma. Subjects will undergo screening in order to determine eligibility.

The study will use a standard 3+3 method of dose escalation. Patients will be enrolled in cohorts of 3. Four dose levels are planned and include 25, 50, 75, and 100 mg of Eryaspase with reduced dose irinotecan. Subjects will be assigned to a dose level in the order of study entry with at least a 3-day stagger in enrollment between individual subjects. With the 3+3 design to be employed, doses are not escalated unless all patients receiving the current dose have been observed for at least 6 weeks and dose-limiting toxicities (DLTs) have been reported. The MTD is defined as the highest dose level where at most 1 of 6 patients experience a dose limiting toxicity (DLT). Three patients will be treated at dose level 0. If 0/3 experience a DLT, 3 new patients will be enrolled at the next higher dose level. If 1/3 experience a DLT, 3 additional patients will be enrolled at the same dose level. If 1/6 patients experience a DLT at any dose level except the highest dose level, 3 new patients will be enrolled at the next higher dose level; if 1/6 patients at the highest dose level experience a DLT, it will be deemed the MTD and the trial will stop. As soon as 2 patients experience a DLT at a given dose level, that dose will be concluded to be above the MTD, dose escalation will cease and 3 new patients will be enrolled at the next lower dose level. If 6 patients were previously treated at that lower dose, the study will halt and that lower dose will be declared the MTD. A subject who withdraws from the escalation phase of the study for reasons other than a DLT will be replaced.

FOLFIRINOX treatment will be given on Day 1 and 15 of the 4 weeks cycle and continued until unacceptable toxicity or disease progression, for a maximum of 12 cycles. Subjects will receive a single intravenous administration of Eryaspase on Day 1 and 15 of 4-weeks cycle.

The study visits are day 1, 8, 15, 22, during cycle 1 and day 1 and 15 during subsequent cycles with a 4-week follow-up period after the end of treatment. Subjects who show at least stable disease based on RECIST 1.1 at the end of the 12-week period (Day 85) are eligible for the continuation of FOLFIRINOX plus eryaspase treatment until disease progression or unacceptable toxicity.

Dose escalation of Eryaspase in combination with FOLFIRINOX

Eryaspase With Modified FOLFIRINOX in Advanced Pancreatic Ductal Adenocarcinoma

A Phase I Dose Escalation Study of Eryaspase in Combination With Modified FOLFIRINOX in Locally Advanced and Metastatic Pancreatic Ductal Adenocarcinoma

The number and percentage of all subjects who experience adverse events (AEs), serious adverse events (SAEs), or abnormal laboratory results according to NCI CTCAE Version 5.0, that occur after Cycle 1, Day 1 will be reported.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment in PAC	NCT03665441	Pancreatic Aden...	eryaspase Gemcitabine plu... Irinotecan plus...	18 Years -	ERYtech Pharma
Eryaspase With Modified FOLFIRINOX in Advanced Pancreatic Ductal Adenocarcinoma	NCT04292743	Locally Advance... Metastatic Panc...	Eryaspase FOLFIRINOX	18 Years -	Georgetown University
Eryaspase With Modified FOLFIRINOX in Advanced Pancreatic Ductal Adenocarcinoma	NCT04292743	Locally Advance... Metastatic Panc...	Eryaspase FOLFIRINOX	18 Years -	Georgetown University

Spots Global Cancer Trial Database for eryaspase

Every month we try and update this database with for eryaspase cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for eryaspase

Every month we try and update this database with for eryaspase cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for eryaspase cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.