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Clinical Trial Results:
A Study of the Safety and Efficacy of the Combination of Gemcitabine and Docetaxel with MORAb-004 in Metastatic Soft Tissue Sarcoma

Summary
EudraCT number	2012-001399-12
Trial protocol	BE NL
Global end of trial date	02 Aug 2016

Results information
Results version number	v2(current)
This version publication date	17 Aug 2019
First version publication date	20 Apr 2019
Other versions	v1
Version creation reason	Correction of full data set Added description in the "Adverse events" section of "Adverse event reporting additional description".

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

MORAb-004-203-STS

ISRCTN number

US NCT number

NCT01574716

WHO universal trial number (UTN)

Sponsor organisation name

Morphotek (a subsidiary of Eisai Inc.)

Sponsor organisation address

210 Welsh Pool Road, Exton, United States, 19341

Public contact

Medical Information, Eisai Europe Ltd., +44 20 8600 1400, LMedInfo@eisai.net

Scientific contact

Medical Information, Eisai Europe Ltd., +44 20 8600 1400, LMedInfo@eisai.net

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

02 Aug 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

02 Aug 2016

Was the trial ended prematurely?

Main objective of the trial

To evaluate the radiologic progression-free survival (PFS) of subjects treated with the combination of gemcitabine/docetaxel plus MORAb-004 versus gemcitabine/docetaxel plus placebo in subjects with metastatic soft tissue sarcoma (mSTS) in 4 defined subgroups: 1. Liposarcoma (excluding pure, well-differentiated sarcoma) 2. Leiomyosarcoma 3. Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (UPS previously characterized as MFH) 4. Other STS, that is, subjects with a histologic diagnosis of high grade sarcoma not otherwise specified (NOS), angiosarcoma, synovial sarcoma, rhabdomyosarcoma, hemagiopericytoma/ solitary fibrous tumor, or other liposarcoma.

Protection of trial subjects

This study was conducted in accordance with standard operating procedures (SOPs) of the sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as required by the following: - Principles of the World Medical Association Declaration of Helsinki (World Medical Association, 2008) - International Council on Harmonisation (ICH) E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - Title 21 of the United States (US) Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and Institutional Review Board (IRB) regulations and applicable sections of US 21 CFR Part 312 - European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country. All suspected unexpected serious adverse reactions were reported, as required, to the Competent Authorities of all involved EU member states. - Article 14, Paragraph 3, and Article 80-2 of the Pharmaceutical Affairs Law (Law No. 145, 1960) for studies conducted in Japan, in addition to Japan’s GCP Subject Information and Informed Consent.

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Aug 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 3

Country: Number of subjects enrolled

Belgium: 10

Country: Number of subjects enrolled

France: 8

Country: Number of subjects enrolled

Italy: 2

Country: Number of subjects enrolled

United States: 186

Country: Number of subjects enrolled

Australia: 16

Worldwide total number of subjects

225

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

166

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Subjects took part in the study at 31 investigative sites in the United States, Australia, Italy, Netherlands, France and Belgium from 07 August 2012 to 02 August 2016.

Screening details

In Part 1, a total of 16 subjects were enrolled and treated in the study. A total of 225 subjects were screened for entry into Part 2 of the study. Of these 225 subjects, 46 were screen failures and 209 were randomized into the study, of which 207 subjects were treated.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer

Blinding implementation details

Part 1 of the study was an open-label, standard 3-plus-3 dose escalation of MORAb-004 (4, 6, and 8 milligram per kilogram [mg/kg]) in combination with gemcitabine/docetaxel (900 milligram per square meter [mg/m^2] and 75 mg/m^2, respectively) infusion. Part 2 of the study was a randomized, double-blind, placebo-controlled study of 8 mg/kg MORAb-004 in combination with gemcitabine/docetaxel infusion versus placebo in combination with gemcitabine/docetaxel infusion.

Are arms mutually exclusive

Yes

Part 1: MORAb-004 4.0 mg/kg + Gemcitabine/Docetaxel

Arm description

Subjects received MORAb-004 4 mg/kg, infusion, intravenously on Days 1 and 8 in combination with gemcitabine 900 mg/m^2, infusion, intravenously on Days 1 and 8 and docetaxel, infusion, intravenously on Day 8 of each 21-day treatment cycle until disease progression (approximately 28 cycles). MORAb-004 was administered after the administration of gemcitabine on Day 1 and after the administration of gemcitabine/docetaxel on Day 8 in each 21-day treatment cycle.

Arm type

Experimental

Investigational medicinal product name

MORAb-004

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received MORAb-004 4 mg/kg, infusion, intravenously on Days 1 and 8 of each 21-day treatment cycle, until disease progression (approximately 28 cycles). MORAb-004 was administered after the administration of gemcitabine on Day 1 and after the administration of gemcitabine/docetaxel on Day 8 in each 21-day treatment cycle.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received gemcitabine 900 mg/m^2, infusion, intravenously on Days 1 and 8 of each 21-day treatment cycle, until disease progression (approximately 28 cycles).

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received docetaxel 75 mg/m^2, infusion, intravenously on Day 8 of each 21-day treatment cycle, until disease progression (approximately 28 cycles).

Part 1: MORAb-004 6.0 mg/kg + Gemcitabine/Docetaxel

Arm description

Subjects received MORAb-004 6 mg/kg, infusion, intravenously on Days 1 and 8 in combination with gemcitabine 900 mg/m^2, infusion, intravenously on Days 1 and 8 and docetaxel 75 mg/m^2, infusion, intravenously on Day 8 of each 21-day treatment cycle until disease progression (approximately 28 cycles). MORAb-004 was administered after the administration of gemcitabine on Day 1 and after the administration of gemcitabine/docetaxel on Day 8 in each 21-day treatment cycle.

Arm type

Experimental

Investigational medicinal product name

MORAb-004

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received MORAb-004 6 mg/kg, infusion, intravenously on Days 1 and 8 of each 21-day treatment cycle, until disease progression (approximately 28 cycles). MORAb-004 was administered after the administration of gemcitabine on Day 1 and after the administration of gemcitabine/docetaxel on Day 8 in each 21-day treatment cycle.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received gemcitabine 900 mg/m^2, infusion, intravenously on Days 1 and 8 of each 21-day treatment cycle, until disease progression (approximately 28 cycles).

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received docetaxel 75 mg/m^2, infusion, intravenously on Day 8 of each 21-day treatment cycle, until disease progression (approximately 28 cycles).

Part 1: MORAb-004 8.0 mg/kg + Gemcitabine/Docetaxel

Arm description

Subjects received MORAb-004 8 mg/kg, infusion, intravenously on Days 1 and 8 in combination with gemcitabine 900 mg/m^2, infusion, intravenously on Days 1 and 8 and docetaxel 75 mg/m^2, infusion, intravenously on Day 8 of each 21-day treatment cycle until disease progression (approximately 28 cycles). MORAb-004 was administered after the administration of gemcitabine on Day 1 and after the administration of gemcitabine/docetaxel on Day 8 in each 21-day treatment cycle.

Arm type

Experimental

Investigational medicinal product name

MORAb-004

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received MORAb-004 8 mg/kg, infusion, intravenously on Days 1 and 8 of each 21-day treatment cycle, until disease progression (approximately 28 cycles). MORAb-004 was administered after the administration of gemcitabine on Day 1 and after the administration of gemcitabine/docetaxel on Day 8 in each 21-day treatment cycle.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received gemcitabine 900 mg/m^2, infusion, intravenously on Days 1 and 8 of each 21-day treatment cycle, until disease progression (approximately 28 cycles).

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received docetaxel 75 mg/m^2, infusion, intravenously on Day 8 of each 21-day treatment cycle, until disease progression (approximately 28 cycles).

Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel

Arm description

Subjects received MORAb-004 8.0 mg/kg, infusion, intravenously on Days 1 and 8 in combination with gemcitabine 900 mg/m^2, infusion, intravenously on Days 1 and 8 and docetaxel 75 mg/m^2, infusion, intravenously on Day 8 of each 21-day treatment cycle for until disease progression (approximately 31 cycles). MORAb-004 was administered after the administration of gemcitabine on Day 1 and after the administration of gemcitabine/docetaxel on Day 8 in each 21-day treatment cycle.

Arm type

Experimental

Investigational medicinal product name

MORAb-004

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received gemcitabine 900 mg/m^2, infusion, intravenously on Days 1 and 8 of each 21-day treatment cycle, until disease progression (approximately 28 cycles).

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received docetaxel 75 mg/m^2, infusion, intravenously on Day 8 of each 21-day treatment cycle, until disease progression (approximately 28 cycles).

Part 2: Placebo + Gemcitabine/Docetaxel

Arm description

Subjects received normal saline (0.9 percent [%] sodium chloride), infusion, intravenously on Days 1 and 8 in combination with gemcitabine 900 mg/m^2, infusion, intravenously on Days 1 and 8 and docetaxel 75 mg/m^2, infusion, intravenously on Day 8 of each 21-day treatment cycle for until disease progression (approximately 31 cycles). Normal saline (0.9% sodium chloride) was administered after the administration of gemcitabine on Day 1 and after the administration of gemcitabine/docetaxel on Day 8 in each 21-day treatment cycle.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravascular use

Dosage and administration details

Subjects received normal saline (0.9% sodium chloride), infusion, intravenously on Days 1 and 8 of each 21-day treatment cycle, until disease progression (approximately 28 cycles). Normal saline (0.9% sodium chloride) was administered after the administration of gemcitabine on Day 1 and after the administration of gemcitabine/docetaxel on Day 8 in each 21-day treatment cycle.

Investigational medicinal product name

Gemcitabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received gemcitabine 900 mg/m^2, infusion, intravenously on Days 1 and 8 of each 21-day treatment cycle.

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received docetaxel 75 mg/m^2, infusion, intravenously on Day 8 of each 21-day treatment cycle.

Number of subjects in period 1	Part 1: MORAb-004 4.0 mg/kg + Gemcitabine/Docetaxel	Part 1: MORAb-004 6.0 mg/kg + Gemcitabine/Docetaxel	Part 1: MORAb-004 8.0 mg/kg + Gemcitabine/Docetaxel	Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel	Part 2: Placebo + Gemcitabine/Docetaxel
Started	3	4	9	139	70
Completed	0	0	0	2	0
Not completed	3	4	9	137	70
Consent withdrawn by subject	-	2	-	5	4
Brain metastases	-	-	-	1	-
Death	3	1	8	76	35
Discontinuation by study sponsor	-	-	1	51	31
Lost to follow-up	-	1	-	3	-
Progressive disease	-	-	-	1	-

Baseline characteristics

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Reporting group title

Part 1: MORAb-004 4.0 mg/kg + Gemcitabine/Docetaxel

Reporting group description

Reporting group title

Part 1: MORAb-004 6.0 mg/kg + Gemcitabine/Docetaxel

Reporting group description

Reporting group title

Part 1: MORAb-004 8.0 mg/kg + Gemcitabine/Docetaxel

Reporting group description

Reporting group title

Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel

Reporting group description

Reporting group title

Part 2: Placebo + Gemcitabine/Docetaxel

Reporting group description

Reporting group values	Part 1: MORAb-004 4.0 mg/kg + Gemcitabine/Docetaxel	Part 1: MORAb-004 6.0 mg/kg + Gemcitabine/Docetaxel	Part 1: MORAb-004 8.0 mg/kg + Gemcitabine/Docetaxel	Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel	Part 2: Placebo + Gemcitabine/Docetaxel	Total
Number of subjects	3	4	9	139	70	225
Age categorical
Units: Subjects
Adults (18-64 years)	3	3	8	103	49	166
From 65-84 years	0	1	1	36	21	59
Gender categorical
Units: Subjects
Female	2	2	3	63	32	102
Male	1	2	6	76	38	123
Race characteristic
Units: Subjects
White	1	3	8	116	57	185
Black or African American	1	1	0	12	9	23
Asian	1	0	1	7	2	11
Chinese	0	0	0	0	2	2
American Indian or Alaskan Native	0	0	0	1	0	1
Other	0	0	0	3	0	3
Ethnicity characteristic
Units: Subjects
Hispanic or Latino	1	0	2	18	8	29
Non-Hispanic or Non-Latino	2	4	7	119	61	193
Not Permitted by Regulatory Authority	0	0	0	2	1	3

End points

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Reporting group title

Part 1: MORAb-004 4.0 mg/kg + Gemcitabine/Docetaxel

Reporting group description

Reporting group title

Part 1: MORAb-004 6.0 mg/kg + Gemcitabine/Docetaxel

Reporting group description

Reporting group title

Part 1: MORAb-004 8.0 mg/kg + Gemcitabine/Docetaxel

Reporting group description

Reporting group title

Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel

Reporting group description

Reporting group title

Part 2: Placebo + Gemcitabine/Docetaxel

Reporting group description

Primary: Part 2: Radiologic Progression-free Survival (PFS)

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End point title

Part 2: Radiologic Progression-free Survival (PFS) ^[1]

End point description

PFS was defined as the time (in weeks) from the date of randomization to the date of first observation of disease progression according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or date of death, regardless of the cause. The intention-to-treat (ITT) population consisted of all randomized subjects and were analyzed according to the treatment assigned by the interactive randomization system (IxRS).

End point type

Primary

End point timeframe

From date of first dose until date of first observation of disease progression, or death due to any cause (up to approximately 3 years)

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be analyzed for the following reporting groups: Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel and Part 2: Placebo +Gemcitabine/Docetaxel.

End point values	Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel	Part 2: Placebo + Gemcitabine/Docetaxel
Number of subjects analysed	139	70
Units: Weeks
median (confidence interval 95%)	18.7 (11.6 to 27.4)	24.1 (11.1 to 36.1)

Part 2: Radiologic Progression-free Survival (PFS)

Comparison groups

Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel v Part 2: Placebo + Gemcitabine/Docetaxel

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6562 ^[2]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.5

Notes
[2] - Two-sided log-rank test.

Secondary: Part 2: Symptomatic Progression-free Survival

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End point title

Part 2: Symptomatic Progression-free Survival ^[3]

End point description

PFS including symptomatic progression was defined as the time (in weeks) from the date of randomization to the date of the first observation of disease progression according to RECIST 1.1, symptomatic progression, or death due to any cause. The ITT population consisted of all randomized subjects and were analyzed according to treatment assigned by the IxRS.

End point type

Secondary

End point timeframe

From date of first dose until date of first observation of disease progression, symptomatic progression, or death due to any cause (up to approximately 3 years)

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be analyzed for the following reporting groups: Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel and Part 2: Placebo +Gemcitabine/Docetaxel.

End point values	Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel	Part 2: Placebo + Gemcitabine/Docetaxel
Number of subjects analysed	139	70
Units: Weeks
median (confidence interval 95%)	18.1 (11.3 to 24)	24 (10.7 to 36.1)

Symptomatic Progression-free Survival

Comparison groups

Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel v Part 2: Placebo + Gemcitabine/Docetaxel

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4469 ^[4]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.57

Notes
[4] - Two-sided log-rank test.

Secondary: Part 2: Overall Survival (OS)

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End point title

Part 2: Overall Survival (OS) ^[5]

End point description

OS was defined as the time (in months) from the date of randomization to the date of death, regardless of the cause. The ITT Population consisted of all randomized subjects and were analyzed according to treatment assigned by the IxRS. Here “99999” refers to the upper limit of confidence interval (CI), which was not estimable since high number of subjects were censored from analysis and therefore we have added 99999 as space-fillers.

End point type

Secondary

End point timeframe

From date of first dose until date of death from any cause (up to approximately 3.5 years)

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be analyzed for the following reporting groups: Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel and Part 2: Placebo +Gemcitabine/Docetaxel.

End point values	Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel	Part 2: Placebo + Gemcitabine/Docetaxel
Number of subjects analysed	139	70
Units: Months
median (confidence interval 95%)	18.3 (16.2 to 21.1)	21.1 (14.2 to 99999)

Overall Survival

Comparison groups

Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel v Part 2: Placebo + Gemcitabine/Docetaxel

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3153 ^[6]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.83

Notes
[6] - Two-sided log-rank test.

Secondary: Part 2: Overall Response Rate (ORR)

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End point title

Part 2: Overall Response Rate (ORR) ^[7]

End point description

ORR was defined as the percentage of subjects with either a complete response (CR) or a partial response (PR) based on RECIST 1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (>) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. The ITT Population consisted of all randomized participants and were analyzed according to treatment assigned by the IxRS.

End point type

Secondary

End point timeframe

From date of first dose until disease progression (up to approximately 3.6 years)

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be analyzed for the following reporting groups: Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel and Part 2: Placebo +Gemcitabine/Docetaxel.

End point values	Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel	Part 2: Placebo + Gemcitabine/Docetaxel
Number of subjects analysed	139	70
Units: percentage of subjects
number (not applicable)	19.4	20.0

Part 2: ORR

Statistical analysis description

Difference = (MORAb 8.0 mg/kg + Gemcitabine/Docetaxel) minus (Placebo + Gemcitabine/Docetaxel). Confidence interval based on a normal approximation to the binomial distribution.

Comparison groups

Part 2: Placebo + Gemcitabine/Docetaxel v Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel

Number of subjects included in analysis

209

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1 ^[8]

Method

2-sided exact p-value

Parameter type

Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-12

upper limit

10.9

Notes
[8] - Two-sided log-rank test.

Secondary: Part 2: Radiologic Progression-free Survival Rate (PFR)

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End point title

Part 2: Radiologic Progression-free Survival Rate (PFR) ^[9]

End point description

Radiologic progression-free survival rate was defined as the percentage of subjects achieving radiologic PFS at the pre-specified time points. The ITT Population consisted of all randomized subjects and were analyzed according to treatment assigned by the IxRS.

End point type

Secondary

End point timeframe

Weeks 12, 24, 48 and 52

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be analyzed for the following reporting groups: Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel and Part 2: Placebo +Gemcitabine/Docetaxel.

End point values	Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel	Part 2: Placebo + Gemcitabine/Docetaxel
Number of subjects analysed	139	70
Units: percentage of subjects
number (not applicable)
12 weeks	57.6	61.8
24 weeks	43.3	51.0
48 weeks	24.5	25.2
52 weeks	20.8	21.4

No statistical analyses for this end point

Secondary: Part 2: Number of Subjects who had Relationship Between MORAb-004 Exposures and Biomarker Levels

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End point title

Part 2: Number of Subjects who had Relationship Between MORAb-004 Exposures and Biomarker Levels ^[10]

End point description

The ITT Population consisted of all randomized subjects and were analyzed according to treatment assigned by the IxRS.

End point type

Secondary

End point timeframe

Up to approximately 3 years

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be analyzed for the following reporting groups: Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel and Part 2: Placebo +Gemcitabine/Docetaxel.

End point values	Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel	Part 2: Placebo + Gemcitabine/Docetaxel
Number of subjects analysed	139	70
Units: subjects	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From date of first dose until 45 days after last dose of study drug (approximately up to 4 years).

Adverse event reporting additional description

Part 2, MORAb-004 8.0mg/kg + Gemcitabine/Docetaxel: 2 subjects discontinued prior to treatment. Part 2, Placebo + Gemcitabine/Docetaxel: 3 subjects randomized but received MORAb are counted in "Part 2, MORAb-004 8.0mg/kg + Gemcitabine/Docetaxel" arm.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

14.1

Reporting group title

Part 1: MORAb-004 4.0mg/kg + Gemcitabine/Docetaxel

Reporting group description

Subjects received MORAb-004 4 milligram per kilogram (mg/kg), infusion, intravenously on Days 1 and 8 in combination with gemcitabine 900 milligram per square meter (mg/m^2), infusion, intravenously on Days 1 and 8 and docetaxel 75 mg/m^2, infusion, intravenously on Day 8 of each 21-day treatment cycle until disease progression (approximately 28 cycles). MORAb-004 was administered after the administration of gemcitabine on Day 1 and after the administration of gemcitabine/docetaxel on Day 8 in each 21-day treatment cycle.

Reporting group title

Part 1: MORAb-004 6.0mg/kg + Gemcitabine/Docetaxel

Reporting group description

Reporting group title

Part 1: MORAb-004 8.0mg/kg + Gemcitabine/Docetaxel

Reporting group description

Reporting group title

Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel

Reporting group description

Reporting group title

Part 2: Placebo + Gemcitabine/Docetaxel

Reporting group description

Subjects received normal saline (0.9 % sodium chloride), infusion, intravenously on Days 1 and 8 in combination with gemcitabine 900 mg/m^2, infusion, intravenously on Days 1 and 8 and docetaxel 75 mg/m^2, infusion, intravenously on Day 8 of each 21-day treatment cycle for until disease progression (approximately 31 cycles). Normal saline (0.9% sodium chloride) was administered after the administration of gemcitabine on Day 1 and after the administration of gemcitabine/docetaxel on Day 8 in each 21-day treatment cycle.

Serious adverse events	Part 1: MORAb-004 4.0mg/kg + Gemcitabine/Docetaxel	Part 1: MORAb-004 6.0mg/kg + Gemcitabine/Docetaxel	Part 1: MORAb-004 8.0mg/kg + Gemcitabine/Docetaxel	Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel	Part 2: Placebo + Gemcitabine/Docetaxel
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	1 / 4 (25.00%)	9 / 9 (100.00%)	106 / 140 (75.71%)	45 / 67 (67.16%)
number of deaths (all causes)	3	1	1	76	35
number of deaths resulting from adverse events	0	0	0	4	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant Pleural Effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastases To Central Nervous System
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tumour Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vena cava thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Capillary leak syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 140 (1.43%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	7 / 140 (5.00%)	2 / 67 (2.99%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	7 / 10	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Systemic Inflammatory Response Syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 140 (1.43%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Generalised Oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infusion Site Extravasation
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mucosal Inflammation
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Non-Cardiac Chest Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oedema Peripheral
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chills
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Cytokine Release Syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypersensitivity
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Respiratory failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
Pulmonary oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	3 / 140 (2.14%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 140 (1.43%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	4 / 140 (2.86%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 140 (1.43%)	2 / 67 (2.99%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural Haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	3 / 140 (2.14%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	3 / 8	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemothorax
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 140 (1.43%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	6 / 140 (4.29%)	3 / 67 (4.48%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 6	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Mental status changes
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Confusional state
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
White Blood Cell Count Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 140 (1.43%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood Creatine Phosphokinase Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood Creatinine Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutrophil Count Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Platelet Count Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	3 / 67 (4.48%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	7 / 7	3 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Accidental Overdose
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clavicle Fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femur Fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hip Fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infusion Related Reaction
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rib Fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Pericardial Effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 140 (1.43%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial Flutter
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial Thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac Arrest
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
Diastolic Dysfunction
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sinus Tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac Failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Depressed level of consciousness
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Embolic stroke
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lethargy
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Memory impairment
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral motor neuropathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 140 (1.43%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transient global amnesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	5 / 140 (3.57%)	4 / 67 (5.97%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	3 / 9	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	3 / 140 (2.14%)	2 / 67 (2.99%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	1 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	2 / 140 (1.43%)	2 / 67 (2.99%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	1 / 3	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	3 / 9 (33.33%)	2 / 140 (1.43%)	3 / 67 (4.48%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 6	1 / 2	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemolytic Uraemic Syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leukocytosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Disseminated Intravascular Coagulation
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Nausea
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	4 / 140 (2.86%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 4	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	3 / 140 (2.14%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal Hernia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	2 / 67 (2.99%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
Constipation
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic Cyst
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	2 / 67 (2.99%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intussusception
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper Gastrointestinal Haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 140 (1.43%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatic Failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Hepatotoxicity
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Portal Vein Thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure acute
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 140 (1.43%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Pain In Extremity
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 140 (1.43%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthralgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Back Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	3 / 67 (4.48%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Groin Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myalgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myositis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal chest pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Cellulitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	8 / 140 (5.71%)	3 / 67 (4.48%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	1 / 8	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	7 / 140 (5.00%)	6 / 67 (8.96%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	2 / 7	1 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Lung Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	3 / 140 (2.14%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary Tract Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	3 / 140 (2.14%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 140 (1.43%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Campylobacter Gastroenteritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Corona Virus Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis Infectious
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia Sepsis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Liver Abscess
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lobar Pneumonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	2 / 67 (2.99%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Neutropenic Sepsis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumocystis Jiroveci Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumocystis Jiroveci Pneumonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Tract Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Soft Tissue Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper Respiratory Tract Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia Primary Atypical
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	6 / 140 (4.29%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 6	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypovolaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypophosphataemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	1 / 67 (1.49%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part 1: MORAb-004 4.0mg/kg + Gemcitabine/Docetaxel	Part 1: MORAb-004 6.0mg/kg + Gemcitabine/Docetaxel	Part 1: MORAb-004 8.0mg/kg + Gemcitabine/Docetaxel	Part 2: MORAb 8.0 mg/kg + Gemcitabine/Docetaxel	Part 2: Placebo + Gemcitabine/Docetaxel
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	4 / 4 (100.00%)	9 / 9 (100.00%)	140 / 140 (100.00%)	66 / 67 (98.51%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	1	0	0	0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	17 / 140 (12.14%)	2 / 67 (2.99%)
occurrences all number	0	0	0	32	3
Hot Flush
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	9 / 140 (6.43%)	0 / 67 (0.00%)
occurrences all number	0	2	0	11	0
Hypotension
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	7 / 140 (5.00%)	7 / 67 (10.45%)
occurrences all number	0	1	0	7	7
Flushing
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	1 / 9 (11.11%)	7 / 140 (5.00%)	4 / 67 (5.97%)
occurrences all number	1	0	1	7	6
General disorders and administration site conditions
Fatigue
subjects affected / exposed	3 / 3 (100.00%)	3 / 4 (75.00%)	6 / 9 (66.67%)	103 / 140 (73.57%)	44 / 67 (65.67%)
occurrences all number	3	6	7	154	64
Pyrexia
subjects affected / exposed	2 / 3 (66.67%)	1 / 4 (25.00%)	4 / 9 (44.44%)	51 / 140 (36.43%)	17 / 67 (25.37%)
occurrences all number	2	1	6	85	27
Oedema peripheral
subjects affected / exposed	1 / 3 (33.33%)	2 / 4 (50.00%)	2 / 9 (22.22%)	59 / 140 (42.14%)	29 / 67 (43.28%)
occurrences all number	1	5	6	100	44
Chills
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	28 / 140 (20.00%)	3 / 67 (4.48%)
occurrences all number	0	1	0	42	4
Influenza like illness
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	15 / 140 (10.71%)	2 / 67 (2.99%)
occurrences all number	0	0	0	20	4
Mucosal Inflammation
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	12 / 140 (8.57%)	6 / 67 (8.96%)
occurrences all number	0	0	0	16	7
Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	11 / 140 (7.86%)	4 / 67 (5.97%)
occurrences all number	0	0	0	19	5
Non-Cardiac Chest Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	7 / 140 (5.00%)	1 / 67 (1.49%)
occurrences all number	0	0	3	8	1
Asthenia
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	7 / 140 (5.00%)	4 / 67 (5.97%)
occurrences all number	0	1	0	16	4
Chest Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	7 / 140 (5.00%)	2 / 67 (2.99%)
occurrences all number	0	0	0	9	3
Catheter Site Rash
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	1	0	0	0
Early satiety
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	2 / 9 (22.22%)	11 / 140 (7.86%)	5 / 67 (7.46%)
occurrences all number	1	0	2	11	5
Dyspnoea
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	41 / 140 (29.29%)	18 / 67 (26.87%)
occurrences all number	0	0	1	56	23
Cough
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	42 / 140 (30.00%)	23 / 67 (34.33%)
occurrences all number	0	0	2	56	27
Epistaxis
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	2 / 9 (22.22%)	18 / 140 (12.86%)	10 / 67 (14.93%)
occurrences all number	0	1	2	22	14
Pleural effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	10 / 140 (7.14%)	3 / 67 (4.48%)
occurrences all number	0	0	2	10	3
Dyspnoea Exertional
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	12 / 140 (8.57%)	7 / 67 (10.45%)
occurrences all number	0	1	0	12	7
Haemoptysis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	2	0	0
Hiccups
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	1	1	0	0	0
Hypoxia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Nasal congestion
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	4 / 140 (2.86%)	5 / 67 (7.46%)
occurrences all number	0	0	1	6	5
Oropharyngeal discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Rhinitis allergic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Wheezing
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	1 / 9 (11.11%)	24 / 140 (17.14%)	12 / 67 (17.91%)
occurrences all number	1	0	1	25	12
Anxiety
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	7 / 140 (5.00%)	2 / 67 (2.99%)
occurrences all number	0	0	1	7	2
Depression
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	7 / 140 (5.00%)	2 / 67 (2.99%)
occurrences all number	0	0	0	7	3
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	3 / 9 (33.33%)	31 / 140 (22.14%)	12 / 67 (17.91%)
occurrences all number	0	0	4	43	20
Platelet Count Decreased
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 9 (0.00%)	20 / 140 (14.29%)	15 / 67 (22.39%)
occurrences all number	1	0	0	41	67
Aspartate Aminotransferase Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	16 / 140 (11.43%)	8 / 67 (11.94%)
occurrences all number	0	0	2	18	15
Blood Alkaline Phosphatase Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	13 / 140 (9.29%)	7 / 67 (10.45%)
occurrences all number	0	0	0	16	8
Neutrophil Count Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	13 / 140 (9.29%)	9 / 67 (13.43%)
occurrences all number	0	0	0	14	31
White Blood Cell Count Decreased
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 9 (0.00%)	11 / 140 (7.86%)	10 / 67 (14.93%)
occurrences all number	1	0	0	33	17
Blood Creatinine Increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	10 / 140 (7.14%)	4 / 67 (5.97%)
occurrences all number	0	0	0	11	7
Blood Albumin Decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	8 / 140 (5.71%)	4 / 67 (5.97%)
occurrences all number	0	0	0	9	5
Lymphocyte count decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	8 / 140 (5.71%)	8 / 67 (11.94%)
occurrences all number	0	0	0	24	28
Weight decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	8 / 140 (5.71%)	2 / 67 (2.99%)
occurrences all number	0	0	2	9	2
Blood calcium decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	7 / 140 (5.00%)	2 / 67 (2.99%)
occurrences all number	0	0	0	9	2
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 9 (0.00%)	10 / 140 (7.14%)	1 / 67 (1.49%)
occurrences all number	1	0	0	10	11
Contusion
subjects affected / exposed	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	2	0	0	0
Tooth fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Nervous system disorders
Headache
subjects affected / exposed	1 / 3 (33.33%)	2 / 4 (50.00%)	3 / 9 (33.33%)	57 / 140 (40.71%)	13 / 67 (19.40%)
occurrences all number	1	2	3	78	20
Dysgeusia
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	31 / 140 (22.14%)	15 / 67 (22.39%)
occurrences all number	0	1	0	44	17
Dizziness
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	16 / 140 (11.43%)	10 / 67 (14.93%)
occurrences all number	0	1	1	19	12
Neuropathy peripheral
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	16 / 140 (11.43%)	16 / 67 (23.88%)
occurrences all number	0	1	2	20	16
Paraesthesia
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	14 / 140 (10.00%)	7 / 67 (10.45%)
occurrences all number	0	1	0	21	7
Peripheral sensory neuropathy
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 9 (0.00%)	8 / 140 (5.71%)	5 / 67 (7.46%)
occurrences all number	1	0	0	8	5
Loss of consciousness
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Neuralgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Hyperaesthesia
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	1	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 3 (66.67%)	1 / 4 (25.00%)	8 / 9 (88.89%)	85 / 140 (60.71%)	37 / 67 (55.22%)
occurrences all number	3	2	20	138	55
Thrombocytopenia
subjects affected / exposed	3 / 3 (100.00%)	0 / 4 (0.00%)	8 / 9 (88.89%)	56 / 140 (40.00%)	28 / 67 (41.79%)
occurrences all number	8	0	29	151	80
Neutropenia
subjects affected / exposed	1 / 3 (33.33%)	2 / 4 (50.00%)	4 / 9 (44.44%)	32 / 140 (22.86%)	15 / 67 (22.39%)
occurrences all number	4	6	10	56	28
Leukopenia
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 9 (0.00%)	20 / 140 (14.29%)	11 / 67 (16.42%)
occurrences all number	3	0	0	30	23
Ear and labyrinth disorders
Deafness Unilateral
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Ear Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Tinnitus
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Eye disorders
Lacrimation increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	8 / 140 (5.71%)	6 / 67 (8.96%)
occurrences all number	0	0	1	10	6
Conjunctivitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	2	0	0
Dry eye
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Vision Blurred
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	1	0	0	0	0
Gastrointestinal disorders
Nausea
subjects affected / exposed	2 / 3 (66.67%)	1 / 4 (25.00%)	5 / 9 (55.56%)	75 / 140 (53.57%)	34 / 67 (50.75%)
occurrences all number	3	1	5	125	49
Constipation
subjects affected / exposed	2 / 3 (66.67%)	1 / 4 (25.00%)	2 / 9 (22.22%)	54 / 140 (38.57%)	25 / 67 (37.31%)
occurrences all number	2	1	3	73	34
Abdominal pain
subjects affected / exposed	1 / 3 (33.33%)	2 / 4 (50.00%)	1 / 9 (11.11%)	11 / 140 (7.86%)	15 / 67 (22.39%)
occurrences all number	1	2	1	12	17
Diarrhoea
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	2 / 9 (22.22%)	61 / 140 (43.57%)	24 / 67 (35.82%)
occurrences all number	1	0	2	112	36
Vomiting
subjects affected / exposed	1 / 3 (33.33%)	2 / 4 (50.00%)	0 / 9 (0.00%)	38 / 140 (27.14%)	11 / 67 (16.42%)
occurrences all number	1	2	0	50	17
Stomatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	17 / 140 (12.14%)	5 / 67 (7.46%)
occurrences all number	0	0	0	24	6
Dyspepsia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	10 / 140 (7.14%)	2 / 67 (2.99%)
occurrences all number	0	0	0	15	2
Abdominal Pain Upper
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	9 / 140 (6.43%)	6 / 67 (8.96%)
occurrences all number	0	2	0	13	6
Dry mouth
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	8 / 140 (5.71%)	5 / 67 (7.46%)
occurrences all number	0	0	0	8	8
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 9 (0.00%)	8 / 140 (5.71%)	4 / 67 (5.97%)
occurrences all number	1	1	0	8	4
Dental Caries
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Flatulence
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	1	0	0	0	0
Frequent bowel movements
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	1	0	0	0
Oral pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	4 / 67 (5.97%)
occurrences all number	0	0	0	2	4
Peptic ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Hepatobiliary disorders
Hyperbilirubinaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	2 / 3 (66.67%)	0 / 4 (0.00%)	2 / 9 (22.22%)	48 / 140 (34.29%)	21 / 67 (31.34%)
occurrences all number	2	0	2	52	21
Rash
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	30 / 140 (21.43%)	23 / 67 (34.33%)
occurrences all number	0	1	1	46	33
Pruritus
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	20 / 140 (14.29%)	3 / 67 (4.48%)
occurrences all number	0	0	0	24	3
Rash Maculo-Papular
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	12 / 140 (8.57%)	1 / 67 (1.49%)
occurrences all number	0	0	0	14	1
Dry Skin
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	10 / 140 (7.14%)	5 / 67 (7.46%)
occurrences all number	0	0	0	11	5
Erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	10 / 140 (7.14%)	4 / 67 (5.97%)
occurrences all number	0	0	0	12	5
Hyperhidrosis
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	1	0	1	0	0
Nail disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Night sweats
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	1	1	0	0
Rash pruritic
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Skin exfoliation
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	1	0	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Urinary tract obstruction
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	1	0	0	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 3 (33.33%)	3 / 4 (75.00%)	1 / 9 (11.11%)	21 / 140 (15.00%)	13 / 67 (19.40%)
occurrences all number	1	3	1	26	14
Pain in extremity
subjects affected / exposed	1 / 3 (33.33%)	2 / 4 (50.00%)	1 / 9 (11.11%)	25 / 140 (17.86%)	13 / 67 (19.40%)
occurrences all number	1	2	1	29	14
Arthralgia
subjects affected / exposed	0 / 3 (0.00%)	3 / 4 (75.00%)	0 / 9 (0.00%)	21 / 140 (15.00%)	15 / 67 (22.39%)
occurrences all number	0	4	0	25	26
Myalgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	34 / 140 (24.29%)	13 / 67 (19.40%)
occurrences all number	0	0	0	48	18
Bone Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	20 / 140 (14.29%)	10 / 67 (14.93%)
occurrences all number	0	0	0	21	10
Musculoskeletal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	14 / 140 (10.00%)	5 / 67 (7.46%)
occurrences all number	0	0	1	16	6
Musculoskeletal chest pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	8 / 140 (5.71%)	2 / 67 (2.99%)
occurrences all number	0	0	0	9	2
Groin pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Metatarsalgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Muscle twitching
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Musculoskeletal stiffness
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Pain in jaw
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Infections and infestations
Cellulitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	9 / 140 (6.43%)	4 / 67 (5.97%)
occurrences all number	0	1	0	10	4
Upper Respiratory Tract Infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	17 / 140 (12.14%)	3 / 67 (4.48%)
occurrences all number	0	0	1	21	3
Urinary tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	13 / 140 (9.29%)	4 / 67 (5.97%)
occurrences all number	0	0	1	17	6
Pneumonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	7 / 140 (5.00%)	2 / 67 (2.99%)
occurrences all number	0	0	0	7	2
Nasopharyngitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	7 / 140 (5.00%)	3 / 67 (4.48%)
occurrences all number	0	0	0	10	3
Sinusitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	7 / 140 (5.00%)	2 / 67 (2.99%)
occurrences all number	0	0	0	8	2
Diverticulitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	1	0	0	0
Gastrointestinal viral infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Lower respiratory tract infection viral
subjects affected / exposed	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	1	0	0	0
Oral Candidiasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	3	0	0
Staphylococcal skin infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 140 (0.00%)	0 / 67 (0.00%)
occurrences all number	0	0	1	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	2 / 3 (66.67%)	0 / 4 (0.00%)	2 / 9 (22.22%)	43 / 140 (30.71%)	16 / 67 (23.88%)
occurrences all number	2	0	2	62	20
Hypokalaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	3 / 9 (33.33%)	19 / 140 (13.57%)	7 / 67 (10.45%)
occurrences all number	0	0	3	27	8
Hyperglycaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	22 / 140 (15.71%)	4 / 67 (5.97%)
occurrences all number	0	0	3	34	6
Dehydration
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	12 / 140 (8.57%)	4 / 67 (5.97%)
occurrences all number	0	0	1	17	5
Hypoalbuminaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	10 / 140 (7.14%)	2 / 67 (2.99%)
occurrences all number	0	0	2	13	2
Hypomagnesaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	8 / 140 (5.71%)	2 / 67 (2.99%)
occurrences all number	0	0	0	10	2
Hyponatraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	8 / 140 (5.71%)	1 / 67 (1.49%)
occurrences all number	0	0	0	11	1
Hypocalcaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	7 / 140 (5.00%)	5 / 67 (7.46%)
occurrences all number	0	0	0	8	6
Increased appetite
subjects affected / exposed	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 140 (0.71%)	0 / 67 (0.00%)
occurrences all number	1	0	0	1	0

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Were there any global substantial amendments to the protocol? Yes

12 Jun 2012

Updated the inclusion and exclusion criteria, specified subjects with prior pelvic irradiation were to begin G/D therapy with a 25% dose reduction (per FDA recommendation), clarified that the MRP2D dose administration, added language to define the circumstances under which an extension of the study would be implemented.

19 Apr 2013

Added additional cohort (Cohort 4) of subjects to re-escalate to 8 mg/kg in Part 1 of the study, amended dose modifications in response to gemcitabine- or docetaxel-related adverse reactions.

20 Aug 2013

Updated the secondary objective and exploratory objectives, updated the inclusion criteria, updated the cohort status to indicate that a fourth cohort was opened and reescalated to 8 mg/kg, updated the enrollment number, updated the biomarker.

06 May 2014

Updated assay for serum drug concentrations was changed from enzyme-linked immunosorbent assay to ECLIA, updated the definition of DLT, updated premedication language and concomitant medication guidance and clarified dosing language of the study drug.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Study of the Safety and Efficacy of the Combination of Gemcitabine and Docetaxel with MORAb-004 in Metastatic Soft Tissue Sarcoma

Trial information

Trial information

Subject disposition

Subject disposition

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Baseline characteristics

End points

End points

Primary: Part 2: Radiologic Progression-free Survival (PFS)

Primary: Part 2: Radiologic Progression-free Survival (PFS)

Secondary: Part 2: Symptomatic Progression-free Survival

Secondary: Part 2: Symptomatic Progression-free Survival

Secondary: Part 2: Overall Survival (OS)

Secondary: Part 2: Overall Survival (OS)

Secondary: Part 2: Overall Response Rate (ORR)

Secondary: Part 2: Overall Response Rate (ORR)

Secondary: Part 2: Radiologic Progression-free Survival Rate (PFR)

Secondary: Part 2: Radiologic Progression-free Survival Rate (PFR)

Secondary: Part 2: Number of Subjects who had Relationship Between MORAb-004 Exposures and Biomarker Levels

Secondary: Part 2: Number of Subjects who had Relationship Between MORAb-004 Exposures and Biomarker Levels

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Substantial protocol amendments (globally)

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Clinical trials

Clinical Trial Results: A Study of the Safety and Efficacy of the Combination of Gemcitabine and Docetaxel with MORAb-004 in Metastatic Soft Tissue Sarcoma

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part 2: Radiologic Progression-free Survival (PFS)

Primary: Part 2: Radiologic Progression-free Survival (PFS)

Secondary: Part 2: Symptomatic Progression-free Survival

Secondary: Part 2: Symptomatic Progression-free Survival

Secondary: Part 2: Overall Survival (OS)

Secondary: Part 2: Overall Survival (OS)

Secondary: Part 2: Overall Response Rate (ORR)

Secondary: Part 2: Overall Response Rate (ORR)

Secondary: Part 2: Radiologic Progression-free Survival Rate (PFR)

Secondary: Part 2: Radiologic Progression-free Survival Rate (PFR)

Secondary: Part 2: Number of Subjects who had Relationship Between MORAb-004 Exposures and Biomarker Levels

Secondary: Part 2: Number of Subjects who had Relationship Between MORAb-004 Exposures and Biomarker Levels

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Study of the Safety and Efficacy of the Combination of Gemcitabine and Docetaxel with MORAb-004 in Metastatic Soft Tissue Sarcoma