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Clinical Trial Results:
A double-blind, randomized, placebo-controlled, Phase I/II Study evaluating the safety, immunogenicity and clinical activity of neoadjuvant treatment with WT1-A10 + AS15 Antigen-Specific Cancer Immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II or III breast cancer.

Summary
EudraCT number	2010-019909-42
Trial protocol	BE DE GB DK
Global end of trial date	14 Nov 2014

Results information
Results version number	v2(current)
This version publication date	20 Jun 2021
First version publication date	05 Mar 2016
Other versions	v1
Version creation reason	Correction of full data set Results have been amended to account for consistency with other registries.

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

113172

ISRCTN number

US NCT number

NCT01220128

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

Rue de l’Institut 89, Rixensart, Belgium, B-1330

Public contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com

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

04 May 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

14 Nov 2014

Global end of trial reached?

Yes

Global end of trial date

14 Nov 2014

Was the trial ended prematurely?

Yes

Main objective of the trial

The study was conducted in 2 consecutive segments with specific objectives: Phase I Segment -Objectives concerning cohorts A, B, C and D: To evaluate the safety and immunogenicity of WT1 ASCI administration in combination with standard treatment. Phase II Segment -To further assess the safety, immunogenicity and the clinical activity of WT1 ASCI in combination with standard treatment per group and in the overall population (i.e., including the patients enrolled during the Phase I segment of the study).

Protection of trial subjects

The vaccine/placebo recipients were to be observed closely for at least 30 minutes with appropriate medical treatment readily available in case of a rare anaphylactic reaction following the administration of vaccine(s)/product(s). For patients in Cohort B and C, the study product administration had to be done at least 60 minutes prior to administration of chemotherapy. The patient was observed closely for at least 30 minutes following the administration of the study product with appropriate medical treatment readily available in case of a rare anaphylactic reaction.

Background therapy

Evidence for comparator

Actual start date of recruitment

11 Apr 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 3

Country: Number of subjects enrolled

Belgium: 9

Country: Number of subjects enrolled

France: 5

Country: Number of subjects enrolled

Germany: 35

Country: Number of subjects enrolled

Italy: 3

Country: Number of subjects enrolled

Russian Federation: 5

Country: Number of subjects enrolled

United States: 6

Worldwide total number of subjects

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)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Out of the 66 enrolled patients, 6 patients did not receive study product doses and were hence excluded prior to study start.

Screening details

During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Double-blind, randomized, placebo-controlled study including 2 segments, a Phase I segment and a Phase II segment. The Phase I segment was a randomized (2:1), double-blinded, placebo-controlled study for cohorts A, B and C and an open label, single treatment schedule study for Cohort D. The Phase II segment was a randomized (2:1), double-blinded, placebo-controlled study for cohorts A, B, C, and E.

Are arms mutually exclusive

Yes

Cohort A-WT1 Group

Arm description

This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of WT1 ASCI according to the treatment schedule.

Arm type

Experimental

Investigational medicinal product name

WT1-A10 + AS15

Investigational medicinal product code

WT1-A10 + AS15

Other name

WT1 ASCI - GSK2302024A

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 6 or 8 injections at 3 weeks apart of WT1 ASCI, injected intramuscularly in the deltoid or lateral region of the thigh.

Investigational medicinal product name

Aromatase inhibitor

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

This treatment consisted of any aromatase inhibitor (e.g. letrozole or exemestane), administered intravenously in Cohort A Groups daily for either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).

Cohort A-Placebo Group

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Placebo

Other name

Pharmaceutical forms

Concentrate and solvent for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 6 or 8 doses at 3 weeks apart of placebo (sucrose/mannitol-based formulation reconstituted with an oil-in-water emulsion), injected intramuscularly in the deltoid or lateral region of the thigh.

Investigational medicinal product name

Aromatase inhibitor

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Cohort B-WT1 Group

Arm description

This group included breast cancer patients who received WT1 ASCI, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Arm type

Experimental

Investigational medicinal product name

WT1-A10 + AS15

Investigational medicinal product code

WT1-A10 + AS15

Other name

WT1 ASCI

Pharmaceutical forms

Powder for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 6 or 8 injections at 3 weeks apart of WT1 ASCI, injected intramuscularly in the deltoid or lateral region of the thigh.

Investigational medicinal product name

5-Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered intravenously in Cohort B, C and D Groups: for the 6 WT1 ASCI/Placebo-dose schedule 3 doses at 3 weeks apart, and for the 8 WT1 ASCI/Placebo-dose schedule 4 doses at 3 weeks apart. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D Group, the administration was on Day 14 of each cycle.

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered intravenously in Cohort B, C and D Groups: for the 6 WT1 ASCI/Placebo-dose schedule 3 doses in Cohort C Groups and 6 doses 3 weeks apart in Cohort B and D Groups, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D Group, the administration was on Day 14 of each cycle.

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered intravenously in Cohort B, C and D Groups: for the 6 WT1 ASCI/placebo-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI/Placebo-dose schedule 4 doses at 3 weeks apart. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D Group, the administration was on Day 14 of each cycle.

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered intravenously in Cohort B, C and D Groups: for the 6 WT1 ASCI/Placebo-dose schedule 6 doses 3 weeks apart (Cohort C patients with this schedule did not receive this treatment), while for the 8 WT1 ASCI/Placebo-dose schedule 4 doses at 3 weeks apart. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D Group, the administration was on Day 14 of each cycle.

Investigational medicinal product name

Epirubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered intravenously in Cohort B, C and D Groups: for the 6 WT1 ASCI/Placebo-dose schedule 3 doses 3 weeks apart, while for the 8 WT1 ASCI/Placebo-dose schedule 4 doses at 3 weeks apart. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D Groups, the administration was on Day 14 of each cycle.

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered intravenously in Cohort B, C and D Groups: only in the 8 WT1 ASCI/Placebo-dose schedule patients received 4 at 3 weeks apart or 12 weekly doses. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D Group, the administration was on Day 14 of each cycle.

Cohort B-Placebo Group

Arm description

This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Placebo

Other name

Pharmaceutical forms

Concentrate and solvent for solution for injection

Routes of administration

Intraventricular use

Dosage and administration details

Subjects received 6 or 8 doses at 3 weeks apart of Placebo (sucrose/mannitol-based formulation reconstituted with an oil-in-water emulsion), injected intramuscularly in the deltoid or lateral region of the thigh.

Investigational medicinal product name

5-Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Epirubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Cohort C-WT1 Group

Arm description

This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of WT1-ASCI, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

Arm type

Experimental

Investigational medicinal product name

WT1-A10 + AS15

Investigational medicinal product code

WT1-A10 + AS15

Other name

WT1 ASCI

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 6 or 8 injections at 3 weeks apart of WT1-ASCI, injected intramuscularly in the deltoid or lateral region of the thigh .

Investigational medicinal product name

Trastuzumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered intravenously in Cohort C Groups: for the 6 WT1 ASCI/Placebo-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI/Placebo-dose schedule 4 doses at 3 weeks apart. The administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle).

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered intravenously in Cohort C Groups in 6 doses at 3 weeks apart, on the same day as WT1 ASCI/placebo administration (Day 1 of each cycle).

Investigational medicinal product name

5-Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Epirubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Cohort C-Placebo Group

Arm description

This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin AUC, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Placebo

Other name

Pharmaceutical forms

Concentrate and solvent for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered intravenously in Cohort C Groups in 6 doses at 3 weeks apart, on the same day as WT1 ASCI/placebo administration (Day 1 of each cycle).

Investigational medicinal product name

Trastuzumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

5-Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Epirubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Cohort D-WT1-D14 Group

Arm description

This group included patients with hormone receptor-positive and HER2 non-overexpressing breast cancer, who received WT1 ASCI, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

Arm type

Experimental

Investigational medicinal product name

WT1-A10 + AS15

Investigational medicinal product code

WT1-A10 + AS15

Other name

WT1 ASCI

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 6 or 8 injections at 3 weeks apart, of WT1 ASCI injected intramuscularly in the deltoid or lateral region of the thigh .

Investigational medicinal product name

5-Fluorouracil

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Epirubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 1 ^[1]	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Started	15	7	9	6	11	4	8
Completed	11	6	6	6	11	4	3
Not completed	4	1	3	0	0	0	5
Adverse event, serious fatal	2	-	-	-	-	-	1
Consent withdrawn by subject	1	-	-	-	-	-	-
Sponsor study termination	-	1	-	-	-	-	1
Adverse event, non-fatal	1	-	-	-	-	-	3
Unspecified	-	-	1	-	-	-	-
Progressive disease	-	-	2	-	-	-	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Out of the 66 enrolled patients, 6 patients did not receive study product doses and were hence excluded prior to study start.

Baseline characteristics

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Reporting group title

Cohort A-WT1 Group

Reporting group description

Reporting group title

Cohort A-Placebo Group

Reporting group description

Reporting group title

Cohort B-WT1 Group

Reporting group description

This group included breast cancer patients who received WT1 ASCI, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Reporting group title

Cohort B-Placebo Group

Reporting group description

This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

Reporting group title

Cohort C-WT1 Group

Reporting group description

Reporting group title

Cohort C-Placebo Group

Reporting group description

This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin AUC, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

Reporting group title

Cohort D-WT1-D14 Group

Reporting group description

Reporting group values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group	Total
Number of subjects	15	7	9	6	11	4	8	60
Age categorical
Units: Subjects
In utero								0
Preterm newborn infants (gestational age < 37 wks)								0
Newborns (0-27 days)								0
Infants and toddlers (28 days-23 months)								0
Children (2-11 years)								0
Adolescents (12-17 years)								0
Adults (18-64 years)								0
From 65-84 years								0
85 years and over								0
Age continuous
Units: years
arithmetic mean (standard deviation)	69.3 ( 10.4 )	70.9 ( 7.1 )	49.3 ( 15.6 )	60.7 ( 9.8 )	52.9 ( 10.6 )	53.3 ( 6.2 )	49.6 ( 8.7 )	-
Gender categorical
Units: Subjects
Female	15	7	9	6	11	4	8	60
Male	0	0	0	0	0	0	0	0

End points

Top of page

Reporting group title

Cohort A-WT1 Group

Reporting group description

Reporting group title

Cohort A-Placebo Group

Reporting group description

Reporting group title

Cohort B-WT1 Group

Reporting group description

This group included breast cancer patients who received WT1 ASCI, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Reporting group title

Cohort B-Placebo Group

Reporting group description

This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

Reporting group title

Cohort C-WT1 Group

Reporting group description

Reporting group title

Cohort C-Placebo Group

Reporting group description

This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin AUC, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

Reporting group title

Cohort D-WT1-D14 Group

Reporting group description

Primary: Number of subjects with severe toxicities

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End point title

Number of subjects with severe toxicities ^[1]

End point description

Severe toxicity was defined as follows: − A Grade 3 or higher toxicity that is related or possibly related to the combined administration of standard treatment and GSK2302024A/placebo − A decrease in Left Ventricular Ejection Fraction (LVEF) from baseline with ≥ 10 points and at < 50% that is related or possibly related to the combined administration of treatment and that is confirmed by a second LVEF assessment within approximately 3 weeks. − A Grade 2 or higher cardiac ischemia/infarction that is related or possibly related to the combined administration of standard treatment and GSK2302024A /placebo. − A Grade 2 or higher allergic reaction occurring within 24 hours following the administration. − A Grade 3 or higher blood/bone marrow toxicity that was considered as related or possibly related to the combined Administration. − A decrease in renal function at the time of administration that was considered as related or possibly related.

End point type

Primary

End point timeframe

From Week 0 to Week 26/32 (period starting from WT1 ASCI/placebo treatment allocation and ending with the concluding Visit i.e.: Week 26 for patients receiving 6 injections and Week 32 for patients receiving 8 injections)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Any severe toxicity	0	0	1	0	1	0	0

No statistical analyses for this end point

Primary: Number of patients with an anti-WT1 humoral response

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End point title

Number of patients with an anti-WT1 humoral response ^[2]

End point description

For initially seronegative patients: post-administration antibody concentration ≥ 9 EU/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-administration antibody concentration.

End point type

Primary

End point timeframe

At post-WT1 ASCI/placebo Dose 4 (Week 13)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	10	4	8	6	11	3	3
Units: Subjects
Anti-WT1 response	10	0	0	0	6	0	2

No statistical analyses for this end point

Primary: Number of patients with adverse events (AEs)

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End point title

Number of patients with adverse events (AEs) ^[3]

End point description

An AE is any untoward medical occurrence in a clinical investigation patient, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse.

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Any AE(s)	15	5	9	6	11	4	7

No statistical analyses for this end point

Primary: Number of subjects with serious adverse events SAE(s)

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End point title

Number of subjects with serious adverse events SAE(s) ^[4]

End point description

A serious adverse event (SAE) is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of hospitalization, causes disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient. In this study, an event which was part of the natural course of the disease under study (i.e., disease progression/recurrence) was captured in the study/as an efficacy measure. Therefore it was not reported as an SAE. Progression/recurrence of the tumor was recorded in the clinical assessments in the electronic case report form (eCRF). Death due to progressive disease was recorded on a specific form in the eCRF but not as an SAE.

End point type

Primary

End point timeframe

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Any SAE(s)	3	0	4	2	5	1	5

No statistical analyses for this end point

Primary: Number of subjects with alanine aminotransferase increased abnormality, by CTCAE maximum grade

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End point title

Number of subjects with alanine aminotransferase increased abnormality, by CTCAE maximum grade ^[5]

End point description

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5)

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	12	5	8	4	6	2	1
Grade 1	2	1	1	2	5	2	2
Grade 2	0	0	0	0	0	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	1	1	0	0	0	0	5

No statistical analyses for this end point

Primary: Number of subjects with alkaline phosphatase increased abnormality, by CTCAE maximum grade

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End point title

Number of subjects with alkaline phosphatase increased abnormality, by CTCAE maximum grade ^[6]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	10	5	8	6	7	3	1
Grade 1	5	1	1	0	4	1	2
Grade 2	0	0	0	0	0	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	1	0	0	0	0	5

No statistical analyses for this end point

Primary: Number of subjects with anemia, by CTCAE maximum grade

Top of page

End point title

Number of subjects with anemia, by CTCAE maximum grade ^[7]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	12	7	1	0	0	0	2
Grade 1	2	0	7	4	7	3	2
Grade 2	1	0	0	0	4	1	0
Grade 3	0	0	1	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	0	0	0	0	0	4

No statistical analyses for this end point

Primary: Number of subjects with aspartate aminotransferase increased abnormality, by CTCAE maximum grade

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End point title

Number of subjects with aspartate aminotransferase increased abnormality, by CTCAE maximum grade ^[8]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	12	4	8	6	7	1	2
Grade 1	3	2	1	0	4	3	1
Grade 2	1	0	0	0	0	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	1	0	0	0	0	5

No statistical analyses for this end point

Primary: Number of subjects with blood bilirubin increased abnormality, by CTCAE maximum grade

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End point title

Number of subjects with blood bilirubin increased abnormality, by CTCAE maximum grade ^[9]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	15	5	9	6	11	2	3
Grade 1	0	1	0	0	0	0	0
Grade 2	0	0	0	0	0	1	0
Grade 3	0	0	0	0	0	1	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	1	0	0	0	0	5

No statistical analyses for this end point

Primary: Number of subjects with creatine increased abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with creatine increased abnormality, by CTCAE maximum grade ^[10]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	11	4	8	5	10	3	3
Grade 1	4	2	1	1	1	1	0
Grade 2	0	0	0	0	0	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	4	1	0	0	0	0	5

No statistical analyses for this end point

Primary: Number of subjects with hemoglobin increased abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with hemoglobin increased abnormality, by CTCAE maximum grade ^[11]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	15	6	9	6	11	4	4
Grade 1	0	1	0	0	0	0	0
Grade 2	0	0	0	0	0	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	0	0	0	0	0	4

No statistical analyses for this end point

Primary: Number of subjects with hypercalcemia abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with hypercalcemia abnormality, by CTCAE maximum grade ^[12]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	14	3	8	6	11	4	3
Grade 1	1	3	1	0	0	0	0
Grade 2	0	0	0	0	0	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	3	1	0	0	0	0	5

No statistical analyses for this end point

Primary: Number of subjects with hyperkalemia abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with hyperkalemia abnormality, by CTCAE maximum grade ^[13]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	15	5	7	6	10	4	3
Grade 1	0	1	1	0	1	0	0
Grade 2	0	0	1	0	0	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	1	0	0	0	0	5

No statistical analyses for this end point

Primary: Number of subjects with hypernatremia abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with hypernatremia abnormality, by CTCAE maximum grade ^[14]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	14	4	9	6	10	4	3
Grade 1	1	2	0	0	0	0	0
Grade 2	0	0	0	0	1	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	1	0	0	0	0	5

No statistical analyses for this end point

Primary: Number of subjects with hypoalbuminemia abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with hypoalbuminemia abnormality, by CTCAE maximum grade ^[15]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	13	6	9	5	9	3	3
Grade 1	1	0	0	1	2	1	0
Grade 2	1	0	0	0	0	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	1	0	0	0	0	5

No statistical analyses for this end point

Primary: Number of subjects with hypocalcemia abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with hypocalcemia abnormality, by CTCAE maximum grade ^[16]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	12	6	5	4	10	3	3
Grade 1	3	0	3	1	1	1	0
Grade 2	0	0	1	1	0	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	1	0	0	0	0	5

No statistical analyses for this end point

Primary: Number of subjects with hypokalemia abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with hypokalemia abnormality, by CTCAE maximum grade ^[17]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	15	6	9	6	10	4	3
Grade 1	0	0	0	0	1	0	0
Grade 2	0	0	1	0	0	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	1	0	0	0	0	5

No statistical analyses for this end point

Primary: Number of subjects with hyponatremia abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with hyponatremia abnormality, by CTCAE maximum grade ^[18]

End point description

End point type

Primary

End point timeframe

During the treatment period and post 30 days post last administration

Notes
[18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	15	6	5	6	11	4	3
Grade 1	0	0	4	0	0	0	0
Grade 2	0	0	0	0	0	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	1	0	0	0	0	5

No statistical analyses for this end point

Primary: Number of subjects with lymphocyte count decreased abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with lymphocyte count decreased abnormality, by CTCAE maximum grade ^[19]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	9	4	0	0	2	1	1
Grade 1	5	2	3	2	3	1	1
Grade 2	1	1	5	2	5	1	2
Grade 3	0	0	1	2	1	1	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	0	0	0	0	0	4

No statistical analyses for this end point

Primary: Number of subjects with lymphocyte count increased abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with lymphocyte count increased abnormality, by CTCAE maximum grade ^[20]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	15	7	9	6	11	4	4
Grade 1	0	0	0	0	0	0	0
Grade 2	0	0	0	0	0	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	0	0	0	0	0	4

No statistical analyses for this end point

Primary: Number of subjects with neutrophil count decreased abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with neutrophil count decreased abnormality, by CTCAE maximum grade ^[21]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	12	6	7	5	10	3	0
Grade 1	3	0	1	1	1	0	0
Grade 2	0	1	1	0	0	0	1
Grade 3	0	0	0	0	0	1	0
Grade 4	0	0	0	0	0	0	3
Grade Unknown	0	0	0	0	0	0	4

No statistical analyses for this end point

Primary: Number of subjects with platelet count decreased abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with platelet count decreased abnormality, by CTCAE maximum grade ^[22]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	14	6	8	5	5	2	2
Grade 1	1	1	1	1	5	2	2
Grade 2	0	0	0	0	1	0	0
Grade 3	0	0	0	0	0	0	0
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	0	0	0	0	0	4

No statistical analyses for this end point

Primary: Number of subjects with white blood cell decreased abnormality, by CTCAE maximum grade

Top of page

End point title

Number of subjects with white blood cell decreased abnormality, by CTCAE maximum grade ^[23]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Grade 0	13	7	6	3	7	2	0
Grade 1	2	0	2	2	4	1	1
Grade 2	0	0	1	1	0	1	0
Grade 3	0	0	0	0	0	0	3
Grade 4	0	0	0	0	0	0	0
Grade Unknown	0	0	0	0	0	0	4

No statistical analyses for this end point

Primary: Number of patients with adverse events (AEs), by CTCAE maximum grade reported

Top of page

End point title

Number of patients with adverse events (AEs), by CTCAE maximum grade reported ^[24]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Any AE(s) Grade 1	6	1	0	0	0	0	0
Any AE(s) Grade 2	6	4	6	0	4	3	2
Any AE(s) Grade 3	3	0	0	5	3	0	1
Any AE(s) Grade 4	0	0	2	1	4	1	4
Any AE(s) Grade 5	0	0	1	0	0	0	0
Any AE(s)	15	5	9	6	11	4	7

No statistical analyses for this end point

Primary: Number of subjects with serious adverse events (SAEs), by CTCAE maximum grade reported

Top of page

End point title

Number of subjects with serious adverse events (SAEs), by CTCAE maximum grade reported ^[25]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Any SAE(s) Grade 1	0	0	0	0	0	0	0
Any SAE(s) Grade 2	1	0	1	0	0	0	0
Any SAE(s) Grade 3	2	0	0	1	1	0	1
Any SAE(s) Grade 4	0	0	2	1	4	1	4
Any SAE(s) Grade 5	0	0	1	0	0	0	0
Any SAE(s)	3	0	4	2	5	1	5

No statistical analyses for this end point

Primary: Number of subjects with adverse events (AEs) assessed by the investigators as causally related to WT1 ASCI treatment, by CTCAE maximum grade reported

Top of page

End point title

Number of subjects with adverse events (AEs) assessed by the investigators as causally related to WT1 ASCI treatment, by CTCAE maximum grade reported ^[26]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Any related AE(s) Grade 1	7	2	0	0	5	0	2
Any related AE(s) Grade 2	4	0	3	0	1	1	4
Any related AE(s) Grade 3	1	0	0	0	1	0	0
Any related AE(s) Grade 4	0	0	0	0	0	0	0
Any related AE(s) Grade 5	0	0	0	0	0	0	0
Any related AE(s)	12	2	3	0	7	1	6

No statistical analyses for this end point

Primary: Number of subjects with serious adverse events (SAEs), assessed by the investigators as causally related to WT1 ASCI treatment, by CTCAE maximum grade reported

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End point title

Number of subjects with serious adverse events (SAEs), assessed by the investigators as causally related to WT1 ASCI treatment, by CTCAE maximum grade reported ^[27]

End point description

End point type

Primary

End point timeframe

During the treatment period and up to 30 days post last administration

Notes
[27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	15	7	9	6	11	4	8
Units: Subjects
Any related SAE(s) Grade 1	0	0	0	0	0	0	0
Any related SAE(s) Grade 2	1	0	0	0	0	0	0
Any related SAE(s) Grade 3	0	0	0	0	1	0	0
Any related SAE(s) Grade 4	0	0	0	0	0	0	0
Any related SAE(s) Grade 5	0	0	0	0	0	0	0
Any related SAE(s)	1	0	0	0	1	0	0

No statistical analyses for this end point

Primary: Number of subjects with breast cancer pathological response

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End point title

Number of subjects with breast cancer pathological response ^[28]

End point description

The pathological response in lymph nodes was evaluated by presence or absence of tumor cells by histopathological examination. Partial responses mark the disappearance of tumor cells, with only small clusters or dispersed cells remaining (more than 90% loss) while complete response indicate no identifiable malignant cells. However, ductal carcinoma in situ may be present.

End point type

Primary

End point timeframe

During the treatment period, up to Week 26/32

Notes
[28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Number of subjects analysed	13	6	9	6	11	4	4
Units: Subjects
Partial respose	4	3	5	3	3	1	3
Complete response	0	0	0	2	6	3	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs were reported during the treatment period and up to 30 days post last administration. SAEs during the entire study period (Week 0 to Week 26/32).

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Cohort A-WT1 Group

Reporting group description

This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy concurrently with administration of WT1 ASCI according to treatment schedule.

Reporting group title

Cohort A-Placebo Group

Reporting group description

Reporting group title

Cohort B-WT1 Group

Reporting group description

This group included breast cancer patients who received WT1-ASCI, Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Reporting group title

Cohort B-Placebo Group

Reporting group description

This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

Reporting group title

Cohort C-WT1 Group

Reporting group description

Reporting group title

Cohort C-Placebo Group

Reporting group description

This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

Reporting group title

Cohort D-WT1-D14 Group

Reporting group description

This group included patients with hormone receptor-positive and HER2 non-overexpressing breast cancer, who received WT1-ASCI, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

Serious adverse events	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 15 (20.00%)	0 / 7 (0.00%)	4 / 9 (44.44%)	2 / 6 (33.33%)	5 / 11 (45.45%)	1 / 4 (25.00%)	5 / 8 (62.50%)
number of deaths (all causes)	0	0	1	0	0	0	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
subjects affected / exposed	1 / 15 (6.67%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	1 / 9 (11.11%)	1 / 6 (16.67%)	4 / 11 (36.36%)	0 / 4 (0.00%)	3 / 8 (37.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 4	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	1 / 9 (11.11%)	1 / 6 (16.67%)	1 / 11 (9.09%)	1 / 4 (25.00%)	2 / 8 (25.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 4 (0.00%)	1 / 8 (12.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vestibular disorder
subjects affected / exposed	1 / 15 (6.67%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoidal haemorrhage
subjects affected / exposed	1 / 15 (6.67%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Polymyalgia rheumatica
subjects affected / exposed	1 / 15 (6.67%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Cohort A-WT1 Group	Cohort A-Placebo Group	Cohort B-WT1 Group	Cohort B-Placebo Group	Cohort C-WT1 Group	Cohort C-Placebo Group	Cohort D-WT1-D14 Group
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 15 (100.00%)	5 / 7 (71.43%)	9 / 9 (100.00%)	6 / 6 (100.00%)	11 / 11 (100.00%)	4 / 4 (100.00%)	7 / 8 (87.50%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
subjects affected / exposed	0 / 15 (0.00%)	1 / 7 (14.29%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Vascular disorders
Hot flush
subjects affected / exposed	2 / 15 (13.33%)	0 / 7 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)
occurrences all number	2	0	2	0	0	0	2
Flushing
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	2	0	0	0	0
General disorders and administration site conditions
Fatigue
alternative assessment type: Systematic
subjects affected / exposed	3 / 15 (20.00%)	1 / 7 (14.29%)	8 / 9 (88.89%)	4 / 6 (66.67%)	7 / 11 (63.64%)	4 / 4 (100.00%)	2 / 8 (25.00%)
occurrences all number	3	1	8	4	7	4	2
Injection site pain
subjects affected / exposed	4 / 15 (26.67%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	4 / 11 (36.36%)	0 / 4 (0.00%)	4 / 8 (50.00%)
occurrences all number	4	0	0	0	4	0	4
Injection site erythema
subjects affected / exposed	5 / 15 (33.33%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	3 / 11 (27.27%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	5	0	0	0	3	0	0
Mucosal inflammation
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	3 / 9 (33.33%)	0 / 6 (0.00%)	3 / 11 (27.27%)	2 / 4 (50.00%)	0 / 8 (0.00%)
occurrences all number	0	0	3	0	3	2	0
Injection site reaction
subjects affected / exposed	2 / 15 (13.33%)	0 / 7 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	2	0	0	0	0
Injection site swelling
subjects affected / exposed	2 / 15 (13.33%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	0	0	2	0	0
Oedema peripheral
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	3 / 9 (33.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	3	0	0	0	0
Chills
subjects affected / exposed	2 / 15 (13.33%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	0	0	0	0	0
Injection site discomfort
subjects affected / exposed	2 / 15 (13.33%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	0	0	0	0	0
Injection site haematoma
subjects affected / exposed	0 / 15 (0.00%)	1 / 7 (14.29%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	3 / 9 (33.33%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	3	0	2	0	0
Epistaxis
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	2	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	2 / 6 (33.33%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	2	2	0	0
Investigations
Weight decreased
subjects affected / exposed	2 / 15 (13.33%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	0	0	0	0	0
Injury, poisoning and procedural complications
Procedural pain
subjects affected / exposed	0 / 15 (0.00%)	1 / 7 (14.29%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	1	0	0	0	0	1
Cardiac disorders
Palpitations
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	2	0	0
Sinus tachycardia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	2	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	5 / 15 (33.33%)	1 / 7 (14.29%)	1 / 9 (11.11%)	0 / 6 (0.00%)	3 / 11 (27.27%)	0 / 4 (0.00%)	2 / 8 (25.00%)
occurrences all number	5	1	1	0	3	0	2
Peripheral sensory neuropathy
subjects affected / exposed	0 / 15 (0.00%)	1 / 7 (14.29%)	2 / 9 (22.22%)	0 / 6 (0.00%)	5 / 11 (45.45%)	2 / 4 (50.00%)	0 / 8 (0.00%)
occurrences all number	0	1	2	0	5	2	0
Dysgeusia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	2 / 9 (22.22%)	3 / 6 (50.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)
occurrences all number	0	0	2	3	0	0	2
Paraesthesia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	2	0	2	0	0
Neuropathy peripheral
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	2	0	0
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	2 / 6 (33.33%)	4 / 11 (36.36%)	0 / 4 (0.00%)	3 / 8 (37.50%)
occurrences all number	0	0	0	2	4	0	3
Anaemia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	2 / 6 (33.33%)	4 / 11 (36.36%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	2	4	0	0
Leukopenia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	3 / 6 (50.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)
occurrences all number	0	0	0	3	0	0	2
Febrile neutropenia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)
occurrences all number	0	0	0	0	0	0	2
Thrombocytopenia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	2	0	0
Gastrointestinal disorders
Nausea
subjects affected / exposed	2 / 15 (13.33%)	0 / 7 (0.00%)	6 / 9 (66.67%)	0 / 6 (0.00%)	8 / 11 (72.73%)	2 / 4 (50.00%)	3 / 8 (37.50%)
occurrences all number	2	0	6	0	8	2	3
Diarrhoea
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	3 / 9 (33.33%)	0 / 6 (0.00%)	3 / 11 (27.27%)	0 / 4 (0.00%)	2 / 8 (25.00%)
occurrences all number	0	0	3	0	3	0	2
Stomatitis
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	2 / 9 (22.22%)	2 / 6 (33.33%)	2 / 11 (18.18%)	0 / 4 (0.00%)	2 / 8 (25.00%)
occurrences all number	0	0	2	2	2	0	2
Constipation
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	4 / 11 (36.36%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	2	0	4	0	0
Vomiting
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	3 / 9 (33.33%)	2 / 6 (33.33%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	3	2	0	0	0
Abdominal pain upper
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	4 / 9 (44.44%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	4	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 15 (0.00%)	1 / 7 (14.29%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	9 / 9 (100.00%)	5 / 6 (83.33%)	8 / 11 (72.73%)	3 / 4 (75.00%)	3 / 8 (37.50%)
occurrences all number	0	0	9	5	8	3	3
Dry skin
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	2	0	0
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	2	0	0
Pruritus
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	2 / 4 (50.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	2	0
Renal and urinary disorders
Pollakiuria
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	2 / 6 (33.33%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	2	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	3 / 15 (20.00%)	2 / 7 (28.57%)	2 / 9 (22.22%)	0 / 6 (0.00%)	3 / 11 (27.27%)	2 / 4 (50.00%)	0 / 8 (0.00%)
occurrences all number	3	2	2	0	3	2	0
Myalgia
subjects affected / exposed	4 / 15 (26.67%)	0 / 7 (0.00%)	4 / 9 (44.44%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	2 / 8 (25.00%)
occurrences all number	4	0	4	0	2	0	2
Bone pain
subjects affected / exposed	2 / 15 (13.33%)	0 / 7 (0.00%)	3 / 9 (33.33%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	3	0	2	0	0
Back pain
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	2 / 9 (22.22%)	2 / 6 (33.33%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	2	2	0	0	0
Pain in extremity
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	3 / 11 (27.27%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	3	0	0
Infections and infestations
Conjunctivitis
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	2	0	0
Gingivitis
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	2	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	2 / 6 (33.33%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	2	0	0	0
Pharyngitis
subjects affected / exposed	0 / 15 (0.00%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	2	0	0
Influenza
subjects affected / exposed	0 / 15 (0.00%)	1 / 7 (14.29%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	2 / 15 (13.33%)	0 / 7 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	0	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

13 Jan 2011

1. Change in placebo from a lyophilized sucrose formulation reconstituted with a 1/500 dilution of SB62 oil-in-water emulsion to a lyophilized sucrose/mannitol formulation reconstituted with the same dilution of the SB62 oil-in-water emulsion. This change was implemented due to differences in cake height of the lyophilized sucrose formulation compared to lyophilized WT1-A10 and CpG 7909, which would compromise the double blinding of the study. 2. Extension of active follow-up of patients from one to three years. This was requested by the Agence Française de Sécurité Sanitaire des Produits the Santé. 3. In the safety Section (Section 9.1.3), the list of autoimmune diseases to be reported has been replaced by a list of potential immune-mediated diseases (pIMDs). pIMDs include autoimmune diseases and other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Moreover, it is specified that all pIMDs will be recorded in the eCRF and reported to GSK Biologicals within 24 hours using the Serious Adverse Event (SAE) screen, regardless of whether the pIMDs are AEs or SAEs. This ensures expedited reporting of all pIMDs. In addition, SAEs related to study treatment are introduced as a separate category of adverse events, to be recorded from receipt of the first study product until the end of follow –up. Contact information for an emergency unblinding request has also been updated. 4. In the sections describing the molecular and immunological read-outs and the translational research, the distinction between the use of fresh tumor samples or Formalin-Fixed, Paraffin Embedded (FFPE) samples for specific tests has been removed. This allows the use of any of these two types of samples in case updated technologies would be employed for specific analyses. Moreover, it is specified that if appropriate, plasma derived from Peripheral Blood Mononuclear Cell (PBMC) purification may be used as backup material for serum in some tests.

26 Aug 2011

• In case of cardiac assessment during treatment, it has been specified that for patients on 18-week regimens, this assessment should be done between Visit 3 and Visit 4, such that results are available at Visit 4. • Instructions for the processing of tissue samples collected from the resected tumor or tumor bed have been adapted. • Based on feedback from investigators during the investigators’ meeting the following additional changes were done: • The extension of a cohort into the Phase II part of the study depends on the outcome of an intermediate assessment of the immunogenicity of the investigational treatment. The serum sample to be used for this evaluation has been changed from a Post-dose 3 sample to a Post-dose 4 sample to ascertain that sufficient time is allowed for an immune response to develop. • The strict timings for screening tests/examinations are made less stringent. All assessments required for screening, except pregnancy testing can be performed within four weeks prior to randomization of the patient. • Exclusion criterion no 13 (Section 4.4) has been rephrased to make clear that only patients receiving therapeutic anticoagulation are excluded from the study. • In the context of postponement of study treatment in an individual patient, the parameters for blood/bone marrow disorders have been adapted for Cohort B and C, such as to avoid frequent postponement of study treatment administration due to side effects of standard treatment. • The tumor imaging at Visit 4 as well as the post-treatment systemic imaging during the presurgery period have been changed from being mandatory to being optional (according to the investigator’s discretion). The description of tumor imaging has been clarified.

08 Apr 2013

• The analysis of the immunogenicity results of the cohort B (unblinded data) evaluating the concurrent administration of the WT1-A10 + AS15 ASCI on day 1 of each cycle of neoadjuvant chemotherapy and during the corticosteroids treatment showed that the above criteria was not fulfilled. Therefore enrolment into the Phase II segment of cohort B has been stopped. But preliminary data has suggested the induction of an anti-WT1 humoral response by the WT1-A10 + AS01B ASCI in absence of concurrent administration of chemotherapy and corticosteroids in two other clinical studies in acute myeloid leukemia. So, the administration of the WT1-A10 + AS15 ASCI will also be evaluated on day 14 of each cycle of neoadjuvant chemotherapy in a new cohort of patients, in order to gain a better understanding of the role of the chemotherapy and corticosteroids on the immune response induced by the WT1-A10 + AS15 ASCI. • The patients in this new cohort, the cohort D, will receive the WT1-A10 + AS15 ASCI at day 14 (D14) of each cycle of the standard neoadjuvant chemotherapy in an open label, non-randomised design. In the absence of a safety signal and if the WT1-A10 + AS15 ASCI induces an adequate immune response according the same rules defined per protocol (see section 3.1.3.1), an additional group of patients with the same eligibility criteria may be recruited in a double blind, randomised phase II segment of the study (Cohort E). These patients will be randomised to receive either WT1-A10 + AS15 ASCI or placebo on D14 of each cycle of neoadjuvant chemotherapy. The patient population eligible for cohorts D and E is presenting a hormone receptor-positive and HER2 non-overexpressing breast cancer. • Also, the assessment of the anti-CpG7909 humoral response and the anti-WT1 T-cell immune response was moved to translational research section as these assessments are not part of the endpoints of the study and will have no direct impact on the study design, i.e. decision making process.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
18 Jul 2014	The study was terminated, based on scientific and medical relevance, due to negative Phase III studies which assessed another study product from same technology platform.	-

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

The Phase II segment was not completed with only 3 patients enrolled in Cohort A. Consequently, analysis for DFS and OS outcomes was cancelled and the collected clinical activity results are to be considered with caution and uninterpretable.

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of subjects with severe toxicities

Primary: Number of subjects with severe toxicities

Primary: Number of patients with an anti-WT1 humoral response

Primary: Number of patients with an anti-WT1 humoral response

Primary: Number of patients with adverse events (AEs)

Primary: Number of patients with adverse events (AEs)

Primary: Number of subjects with serious adverse events SAE(s)

Primary: Number of subjects with serious adverse events SAE(s)

Primary: Number of subjects with alanine aminotransferase increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with alanine aminotransferase increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with alkaline phosphatase increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with alkaline phosphatase increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with anemia, by CTCAE maximum grade

Primary: Number of subjects with anemia, by CTCAE maximum grade

Primary: Number of subjects with aspartate aminotransferase increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with aspartate aminotransferase increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with blood bilirubin increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with blood bilirubin increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with creatine increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with creatine increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with hemoglobin increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with hemoglobin increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with hypercalcemia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hypercalcemia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hyperkalemia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hyperkalemia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hypernatremia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hypernatremia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hypoalbuminemia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hypoalbuminemia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hypocalcemia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hypocalcemia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hypokalemia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hypokalemia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hyponatremia abnormality, by CTCAE maximum grade

Primary: Number of subjects with hyponatremia abnormality, by CTCAE maximum grade

Primary: Number of subjects with lymphocyte count decreased abnormality, by CTCAE maximum grade

Primary: Number of subjects with lymphocyte count decreased abnormality, by CTCAE maximum grade

Primary: Number of subjects with lymphocyte count increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with lymphocyte count increased abnormality, by CTCAE maximum grade

Primary: Number of subjects with neutrophil count decreased abnormality, by CTCAE maximum grade

Primary: Number of subjects with neutrophil count decreased abnormality, by CTCAE maximum grade

Primary: Number of subjects with platelet count decreased abnormality, by CTCAE maximum grade

Primary: Number of subjects with platelet count decreased abnormality, by CTCAE maximum grade

Primary: Number of subjects with white blood cell decreased abnormality, by CTCAE maximum grade

Primary: Number of subjects with white blood cell decreased abnormality, by CTCAE maximum grade

Primary: Number of patients with adverse events (AEs), by CTCAE maximum grade reported

Primary: Number of patients with adverse events (AEs), by CTCAE maximum grade reported

Primary: Number of subjects with serious adverse events (SAEs), by CTCAE maximum grade reported

Primary: Number of subjects with serious adverse events (SAEs), by CTCAE maximum grade reported

Primary: Number of subjects with adverse events (AEs) assessed by the investigators as causally related to WT1 ASCI treatment, by CTCAE maximum grade reported

Primary: Number of subjects with adverse events (AEs) assessed by the investigators as causally related to WT1 ASCI treatment, by CTCAE maximum grade reported

Primary: Number of subjects with serious adverse events (SAEs), assessed by the investigators as causally related to WT1 ASCI treatment, by CTCAE maximum grade reported

Primary: Number of subjects with serious adverse events (SAEs), assessed by the investigators as causally related to WT1 ASCI treatment, by CTCAE maximum grade reported

Primary: Number of subjects with breast cancer pathological response

Primary: Number of subjects with breast cancer pathological response

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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