Trial Outcomes & Findings for Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment in PAC (NCT NCT03665441)

NCT ID: NCT03665441

Last Updated: 2022-10-18

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

512 participants

Primary outcome timeframe

~12 months

Results posted on

2022-10-18

Participant Flow

Participant milestones

Participant milestones
Measure	Eryaspase Plus Chemotherapy 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	Chemotherapy Alone 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
Overall Study STARTED	255	257
Overall Study COMPLETED	216	240
Overall Study NOT COMPLETED	39	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Eryaspase Plus Chemotherapy 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	Chemotherapy Alone 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
Overall Study survival follow up ongoing	23	0
Overall Study Patients ongoing on treatment	9	6
Overall Study Randomized but not treated	7	11

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eryaspase Plus Chemotherapy n=255 Participants 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	Chemotherapy Alone n=257 Participants 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	Total n=512 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	140 Participants n=99 Participants	142 Participants n=107 Participants	282 Participants n=206 Participants
Age, Categorical >=65 years	115 Participants n=99 Participants	115 Participants n=107 Participants	230 Participants n=206 Participants
Age, Continuous	62.0 years STANDARD_DEVIATION 10.29 • n=99 Participants	62.5 years STANDARD_DEVIATION 9.72 • n=107 Participants	62.2 years STANDARD_DEVIATION 10 • n=206 Participants
Sex: Female, Male Female	121 Participants n=99 Participants	124 Participants n=107 Participants	245 Participants n=206 Participants
Sex: Female, Male Male	134 Participants n=99 Participants	133 Participants n=107 Participants	267 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants	3 Participants n=107 Participants	4 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	6 Participants n=99 Participants	1 Participants n=107 Participants	7 Participants n=206 Participants
Race (NIH/OMB) White	235 Participants n=99 Participants	248 Participants n=107 Participants	483 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	12 Participants n=99 Participants	5 Participants n=107 Participants	17 Participants n=206 Participants
Region of Enrollment United States	19 participants n=99 Participants	20 participants n=107 Participants	39 participants n=206 Participants
Region of Enrollment Europe	236 participants n=99 Participants	237 participants n=107 Participants	473 participants n=206 Participants
ECOG PS ECOG 0	107 participants n=99 Participants	105 participants n=107 Participants	212 participants n=206 Participants
ECOG PS ECOG 1	148 participants n=99 Participants	152 participants n=107 Participants	300 participants n=206 Participants
Time from initial diagnosis of advanced disease to randomization <6 months	79 Participants n=99 Participants	74 Participants n=107 Participants	153 Participants n=206 Participants
Time from initial diagnosis of advanced disease to randomization >=6 months	176 Participants n=99 Participants	183 Participants n=107 Participants	359 Participants n=206 Participants

PRIMARY outcome

Timeframe: ~12 months

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

Outcome measures

Outcome measures
Measure	Eryaspase Plus Chemotherapy n=255 Participants 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	Chemotherapy Alone n=257 Participants 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
Overall Survival (OS)	7.5 months Interval 6.5 to 8.3	6.7 months Interval 5.4 to 7.5

SECONDARY outcome

Timeframe: ~24 weeks

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.

Outcome measures

Outcome measures
Measure	Eryaspase Plus Chemotherapy n=255 Participants 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	Chemotherapy Alone n=257 Participants 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
Progression Free Survival (PFS)	3.7 months Interval 3.4 to 4.1	3.4 months Interval 2.0 to 3.7

SECONDARY outcome

Timeframe: ~24 weeks

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.

Outcome measures

Outcome measures
Measure	Eryaspase Plus Chemotherapy n=255 Participants 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	Chemotherapy Alone n=257 Participants 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
Objective Response Rate (ORR)	41 Participants	32 Participants

SECONDARY outcome

Timeframe: ~24 weeks

To compare the DoR between the 2 treatment arms

Outcome measures

Outcome measures
Measure	Eryaspase Plus Chemotherapy n=255 Participants 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	Chemotherapy Alone n=257 Participants 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
Duration of Response (DoR)	5.7 months Interval 3.9 to 7.4	6.8 months Interval 2.8 to 7.4

SECONDARY outcome

Timeframe: ~24 weeks

To compare the between the 2 treatment arms

Outcome measures

Outcome measures
Measure	Eryaspase Plus Chemotherapy n=255 Participants 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	Chemotherapy Alone n=257 Participants 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
Disease Control Rate (DCR)	147 Participants	126 Participants

SECONDARY outcome

Timeframe: ~9 months

Population: 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.

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

Outcome measures

Outcome measures
Measure	Eryaspase Plus Chemotherapy n=248 Participants 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	Chemotherapy Alone n=246 Participants 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
Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v5.0 Number of patients with treatment emergent adverse events (TEAE)	248 participants	246 participants
Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v5.0 number of patients with TEAE >= Grade 3	195 participants	176 participants
Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v5.0 Number of patients with TE SAE	122 participants	105 participants
Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v5.0 Number of patients with TEAEs leading to study drug discontinuation	46 participants	41 participants
Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v5.0 Number of patients with TE SAE with outcome of death	14 participants	9 participants

SECONDARY outcome

Timeframe: ~1 year

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Eryaspase Plus Chemotherapy n=228 Participants 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	Chemotherapy Alone n=229 Participants 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
Time to Quality of Life Questionnaire EORTC QLQ-C30 First Worsening in Global Health Status Analysis	4.0 months Interval 3.1 to 5.1	3.6 months Interval 2.8 to 4.7

Adverse Events

Eryaspase Plus Chemotherapy

Serious events: 122 serious events

Other events: 248 other events

Deaths: 209 deaths

Chemotherapy Alone

Serious events: 105 serious events

Other events: 244 other events

Deaths: 211 deaths

Serious adverse events

Other adverse events

Additional Information

Anu Gupta, Senior Study Team Lead

Erytech Pharma Inc

Phone: 7327424937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has rights to the first publication for up to 18 months after study completion or termination, or until sponsor determines it does not plan to publish the study results. Following this the Institution and/or Principal Investigator may publish data or results generated at Institution; provided, the proposed publication or presentation is submitted to the Sponsor at least 45 days prior to the date of the proposed publication or presentation for review and approval.
Publication restrictions are in place

Restriction type: OTHER

Measure	Eryaspase Plus Chemotherapy n=248 participants at risk 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	Chemotherapy Alone n=246 participants at risk 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
General disorders Asthenia	75.0% 186/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	29.7% 73/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Gastrointestinal disorders Diarrhoea	53.2% 132/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	43.5% 107/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Blood and lymphatic system disorders Anaemia	51.6% 128/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	39.4% 97/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Gastrointestinal disorders Nausea	53.2% 132/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	36.2% 89/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Blood and lymphatic system disorders Neutropenia	43.5% 108/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	37.8% 93/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Gastrointestinal disorders Abdominal pain	38.7% 96/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	34.1% 84/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Blood and lymphatic system disorders Thrombocytopenia	30.2% 75/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	29.3% 72/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
General disorders Pyrexia	29.4% 73/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	22.8% 56/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Gastrointestinal disorders Decreased appetite	31.0% 77/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	25.2% 62/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Nervous system disorders Neuropathy peripheral	27.8% 69/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	25.2% 62/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Gastrointestinal disorders Constipation	27.8% 69/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	25.2% 62/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Gastrointestinal disorders Vomiting	27.8% 69/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	23.2% 57/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Gastrointestinal disorders Oral disorder	23.4% 58/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	24.4% 60/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Skin and subcutaneous tissue disorders Alopecia	25.8% 64/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	20.7% 51/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Musculoskeletal and connective tissue disorders Back pain	14.9% 37/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	9.8% 24/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.7% 34/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	9.8% 24/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Metabolism and nutrition disorders Hypokalaemia	11.7% 29/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	10.6% 26/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Investigations Weight decreased	14.1% 35/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	5.7% 14/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
General disorders Oedema	26.2% 65/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	19.1% 47/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Investigations Transaminases increased	12.1% 30/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	7.3% 18/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Blood and lymphatic system disorders Leukopenia	11.3% 28/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	6.5% 16/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Musculoskeletal and connective tissue disorders Arthralgia	8.9% 22/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	8.5% 21/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Nervous system disorders Headache	11.7% 29/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	5.7% 14/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Musculoskeletal and connective tissue disorders Myalgia	10.1% 25/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	6.5% 16/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Respiratory, thoracic and mediastinal disorders Epistaxis	8.5% 21/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	6.5% 16/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Psychiatric disorders Sleep disorder	6.5% 16/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	7.7% 19/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Nervous system disorders Dysgeusia	8.1% 20/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	5.7% 14/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Investigations Blood albumin decreased	6.0% 15/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	6.5% 16/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Hepatobiliary disorders Hyperbilirubinaemia	7.3% 18/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	4.1% 10/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Investigations Gamma-glutamyltransferase increased	6.5% 16/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	5.3% 13/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Blood and lymphatic system disorders Lymphopenia	7.7% 19/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	4.1% 10/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Skin and subcutaneous tissue disorders Rash	7.3% 18/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	4.1% 10/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Infections and infestations Urinary tract infection	5.2% 13/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	6.1% 15/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Gastrointestinal disorders Flatulence	7.7% 19/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	3.3% 8/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Psychiatric disorders Anxiety	5.2% 13/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	5.3% 13/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Investigations Blood alkaline phosphatase increased	6.0% 15/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	4.1% 10/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Respiratory, thoracic and mediastinal disorders Cough	5.6% 14/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	4.5% 11/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
General disorders General physical health deterioration	6.9% 17/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	2.8% 7/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Skin and subcutaneous tissue disorders Pruritus	4.4% 11/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	5.3% 13/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
General disorders Chills	6.9% 17/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	2.4% 6/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Gastrointestinal disorders Ascites	6.0% 15/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	2.8% 7/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Nervous system disorders Dizziness	4.8% 12/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	4.1% 10/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Skin and subcutaneous tissue disorders Dry skin	6.0% 15/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	2.8% 7/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Musculoskeletal and connective tissue disorders Pain in extremity	4.8% 12/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	4.1% 10/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	4.8% 12/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	4.1% 10/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Gastrointestinal disorders Gastroesophageal reflux	6.0% 15/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	2.4% 6/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)
Gastrointestinal disorders Dyspepsia	4.8% 12/248 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)	2.8% 7/246 • 9 months (Adverse events were monitored for approximately 9 months and mortality assessed for approximately 12 months.)