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Clinical Trial Results:
An open-label, randomized, controlled, multicenter, phase II study evaluating safety and efficacy of intratumorally administered Intuvax pre-nephrectomy followed by Sunitinib post-nephrectomy, compared to Sunitinib post-nephrectomy in metastatic renal cell carcinoma patients

Summary
EudraCT number	2014-004510-28
Trial protocol	SE CZ HU LV GB ES
Global end of trial date	17 Jul 2019

Results information
Results version number	v2(current)
This version publication date	13 Nov 2021
First version publication date	24 May 2020
Other versions	v1
Version creation reason	New data added to full data set Correction of full data set Data added from survival follow-up and minor corrections of data.

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

IM-201

ISRCTN number

US NCT number

NCT02432846

WHO universal trial number (UTN)

Sponsor organisation name

Immunicum AB

Sponsor organisation address

Östermalmstorg 5, Stockholm, Sweden,

Public contact

Chief Medical Officer , Immunicum AB, +46 (0)8 732 84 00, info@immunicum.com

Scientific contact

Chief Medical Officer , Immunicum AB, +46 (0)8 732 84 00, info@immunicum.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

17 Jul 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

17 Jul 2019

Global end of trial reached?

Yes

Global end of trial date

17 Jul 2019

Was the trial ended prematurely?

Main objective of the trial

The primary objectives are: - To evaluate median overall survival (OS) from randomization in metastatic renal cell carcinoma (mRCC) patients overall and by subgroup, i.e. in high-risk and in intermediate-risk patients separately, receiving two (2) vaccine doses of Intuvax pre-nephrectomy, followed by sunitinib initiated five (5) to eight (8) weeks post-nephrectomy and in non-vaccinated mRCC patients receiving sunitinib initiated five (5) to eight (8) weeks post-nephrectomy - To evaluate 18-month survival rate from randomization in mRCC patients overall and by subgroup, i.e. in high-risk and in intermediaterisk patients separately, receiving two (2) vaccine doses of Intuvax prenephrectomy followed by sunitinib post-nephrectomy and in nonvaccinated patients receiving sunitinib post-nephrectomy

Protection of trial subjects

The final study protocol, including substantial amendments, and the final version of the subject information and consent form, were reviewed and approved by Independent Ethics Committee and Institutional Review board prior to inclusion of subjects. The study was conducted in compliance with the protocol, regulatory requirements, good clinical practice and the ethical principles of the latest revision of the Declaration of Helsinki as adopted by the World Medical Association. All subjects received written and verbal information regarding the study at a prior interview. The given information emphasized that participation in the study was voluntary and that the subject could withdraw from the study at any time and for any reason. All subjects were given the opportunity to ask questions about the study and were given sufficient time to decide whether to participate in the study.

Background therapy

Evidence for comparator

Actual start date of recruitment

28 Apr 2015

Long term follow-up planned

Yes

Long term follow-up rationale

Efficacy

Long term follow-up duration

5 Years

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 18

Country: Number of subjects enrolled

Sweden: 31

Country: Number of subjects enrolled

United Kingdom: 4

Country: Number of subjects enrolled

United States: 2

Country: Number of subjects enrolled

Czech Republic: 6

Country: Number of subjects enrolled

France: 4

Country: Number of subjects enrolled

Hungary: 5

Country: Number of subjects enrolled

Latvia: 6

Country: Number of subjects enrolled

Poland: 12

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

The first patient's first visit was 28 April 2015 and last patient's last visit was 17 June 2019. Patients were recruited from Sweden, France, United States, Czech Republic, Latvia, Poland, Spain, Hungary, United Kingdom.

Screening details

117 patients with newly diagnosed metastatic renal cell cancer were screened according to the inclusion and exclusion criteria. The 88 eligible patients were randomized to either of two treatments: intuvax + sunitinib or sunitinib-only. Patients were stratified according to Heng criteria, as either high-risk or intermediate-risk.

Period 1 title

Overall period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Intuvax + sunitinib, high-risk

Arm description

Intuvax + sunitinib, high-risk stratum

Arm type

Experimental

Investigational medicinal product name

Ilixadencel (formerly known as Intuvax)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intratumoral use

Dosage and administration details

Two (2) doses of ilixadencel (formerly known as Intuvax) cell suspension (10x10^6 DCs) administered intratumorally into the primary tumor 14 ±3 days apart followed by nephrectomy.

Investigational medicinal product name

Sunitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Treatment was initiated five (5) to eight (8) weeks after nephrectomy. Administered in accordance with SmPC / USPI.

Sunitinib-only, high-risk

Arm description

Sunitinib-only, high-risk stratum

Arm type

Active comparator

Investigational medicinal product name

Sunitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Treatment was initiated five (5) to eight (8) weeks after nephrectomy. Administered in accordance with SmPC / USPI.

Intuvax + sunitinib, intermediate-risk

Arm description

Intuvax + sunitinib, intermediate-risk stratum

Arm type

Experimental

Investigational medicinal product name

Sunitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Treatment was initiated five (5) to eight (8) weeks after nephrectomy. Administered in accordance with SmPC / USPI.

Investigational medicinal product name

Ilixadencel (formerly known as Intuvax)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intratumoral use

Dosage and administration details

Two (2) doses of ilixadencel (formerly known as Intuvax) cell suspension (10x10^6 DCs) administered intratumorally into the primary tumor 14 ±3 days apart followed by nephrectomy.

Sunitinib-only, intermediate-risk

Arm description

Sunitinib-only, intermediate-risk stratum

Arm type

Active comparator

Investigational medicinal product name

Sunitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Treatment was initiated five (5) to eight (8) weeks after nephrectomy. Administered in accordance with SmPC / USPI.

Intuvax + sunitinib, total (both strata)

Arm description

Intuvax + sunitinib, high and intermediate risk strata combined

Arm type

Experimental

Investigational medicinal product name

Sunitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Treatment was initiated five (5) to eight (8) weeks after nephrectomy. Administered in accordance with SmPC / USPI.

Investigational medicinal product name

Ilixadencel (formerly known as Intuvax)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intratumoral use

Dosage and administration details

Two (2) doses of ilixadencel (formerly known as Intuvax) cell suspension (10x10^6 DCs) administered intratumorally into the primary tumor 14 ±3 days apart followed by nephrectomy.

Sunitinib-only, total (both strata)

Arm description

Sunitinib-only, high and intermediate risk strata combined

Arm type

Active comparator

Investigational medicinal product name

Sunitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Treatment was initiated five (5) to eight (8) weeks after nephrectomy. Administered in accordance with SmPC / USPI.

Number of subjects in period 1	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)
Started	17	8	41	22	58	30
Completed	2	0	17	8	19	8
Not completed	15	8	24	14	39	22
Adverse event, serious fatal	3	2	4	3	7	5
Consent withdrawn by subject	2	-	1	1	3	1
Disease progression	8	5	15	9	23	14
Adverse event, non-fatal	-	1	1	-	1	1
Investigator's request	2	-	-	-	2	-
Other	-	-	2	1	2	1
Lost to follow-up	-	-	1	-	1	-

Baseline characteristics

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Reporting group title

Intuvax + sunitinib, high-risk

Reporting group description

Intuvax + sunitinib, high-risk stratum

Reporting group title

Sunitinib-only, high-risk

Reporting group description

Sunitinib-only, high-risk stratum

Reporting group title

Intuvax + sunitinib, intermediate-risk

Reporting group description

Intuvax + sunitinib, intermediate-risk stratum

Reporting group title

Sunitinib-only, intermediate-risk

Reporting group description

Sunitinib-only, intermediate-risk stratum

Reporting group title

Intuvax + sunitinib, total (both strata)

Reporting group description

Intuvax + sunitinib, high and intermediate risk strata combined

Reporting group title

Sunitinib-only, total (both strata)

Reporting group description

Sunitinib-only, high and intermediate risk strata combined

Reporting group values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	Total
Number of subjects	17	8	41	22	58	30
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
85 years and over
Age continuous
Age at Screening Visit
Units: years
arithmetic mean (standard deviation)	62.0 ± 9.6	60.5 ± 7.7	61.0 ± 8.4	65.5 ± 10.3	61.3 ± 8.7	64.2 ± 9.8	-
Gender categorical
Units: Subjects
Female	2	2	11	7	13	9	22
Male	15	6	30	15	45	21	66
Race
Units: Subjects
Unknown	1	2	0	0	1	2	3
White	16	6	41	22	57	28	85
Karnofsky Performance Status
Karnofsky Performance Status (KPS) at baseline
Units: Subjects
100%	2	1	17	9	19	10	29
90%	10	2	19	8	29	10	39
80%	5	3	5	5	10	8	18
70%	0	2	0	0	0	2	2
<70%	0	0	0	0	0	0	0
Primary Tumor Stage
Tumor stage defined by AJCC classification system. As given by the inclusion criterion 3, the primary tumor was for all patients at least 4 cm in the greatest dimension (T1b, or higher).
Units: Subjects
T1b	0	0	9	2	9	2	11
T2	0	0	1	0	1	0	1
T2a	4	0	5	3	9	3	12
T2b	1	0	4	0	5	0	5
T3	3	2	2	1	5	3	8
T3a	5	4	11	10	16	14	30
T3b	1	1	1	2	2	3	5
T4	3	1	8	4	11	5	16
Regional Lymph Node Tumor Stage
Tumor stage defined by AJCC classification system.
Units: Subjects
NX	3	1	7	4	10	5	15
N0	7	4	20	7	27	11	38
N1	7	3	14	11	21	14	35
Distant Metastasis Tumor Stage
Tumor stage defined by AJCC classification system.
Units: Subjects
M0	0	0	0	0	0	0	0
M1	17	8	41	22	58	30	88
Height
Height at baseline
Units: cm
arithmetic mean (standard deviation)	173.0 ± 12.8	177.1 ± 10.9	174.4 ± 9.4	170.3 ± 10.8	173.9 ± 10.4	172.1 ± 11.1	-
Weight
Weight at baseline
Units: kilogram(s)
arithmetic mean (standard deviation)	77.8 ± 13.8	78.6 ± 8.8	86.4 ± 20.3	84.4 ± 20.1	83.8 ± 18.9	82.9 ± 17.8	-
mRCC duration
Range from mRCC diagnosis to Screening Visit.
Units: days
median (full range (min-max))	20 (3 to 52)	20.0 (4 to 36)	18.0 (4 to 83)	26.5 (5 to 104)	18.5 (3 to 83)	25.0 (4 to 104)	-

Subject analysis set title

FAS

Subject analysis set type

Full analysis

Subject analysis set description

All patients randomized being evaluable for any high or intermediate stratum related efficacy endpoint.

Subject analysis set title

PPS

Subject analysis set type

Per protocol

Subject analysis set description

All patients randomized to Intuvax who had both doses of Intuvax administered or subject randomized to sunitinib alone, both having the nephrectomy and who continued the trial without any major protocol violations that could interfere with the objectives of this study. Analyses of primary endpoints related to each stratum were repeated using the PPS.

Subject analysis set title

SAF

Subject analysis set type

Safety analysis

Subject analysis set description

All randomized patients who had at least 1 assessment made at Screening. Safety summaries were performed on the safety set.

Subject analysis sets values	FAS	PPS	SAF
Number of subjects	86	73	88
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
85 years and over
Age continuous
Age at Screening Visit
Units: years
arithmetic mean (standard deviation)	±	±	62.3 ± 9.1
Gender categorical
Units: Subjects
Female			22
Male			66
Race
Units: Subjects
Unknown			3
White			85
Karnofsky Performance Status
Karnofsky Performance Status (KPS) at baseline
Units: Subjects
100%			29
90%			39
80%			18
70%			2
<70%			0
Primary Tumor Stage
Tumor stage defined by AJCC classification system. As given by the inclusion criterion 3, the primary tumor was for all patients at least 4 cm in the greatest dimension (T1b, or higher).
Units: Subjects
T1b			11
T2			1
T2a			12
T2b			5
T3			8
T3a			30
T3b			5
T4			16
Regional Lymph Node Tumor Stage
Tumor stage defined by AJCC classification system.
Units: Subjects
NX			15
N0			38
N1			35
Distant Metastasis Tumor Stage
Tumor stage defined by AJCC classification system.
Units: Subjects
M0			0
M1			88
Height
Height at baseline
Units: cm
arithmetic mean (standard deviation)	±	±	173.3 ± 10.6
Weight
Weight at baseline
Units: kilogram(s)
arithmetic mean (standard deviation)	±	±	83.5 ± 18.4
mRCC duration
Range from mRCC diagnosis to Screening Visit.
Units: days
median (full range (min-max))			20.5 (3 to 104)

End points

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Reporting group title

Intuvax + sunitinib, high-risk

Reporting group description

Intuvax + sunitinib, high-risk stratum

Reporting group title

Sunitinib-only, high-risk

Reporting group description

Sunitinib-only, high-risk stratum

Reporting group title

Intuvax + sunitinib, intermediate-risk

Reporting group description

Intuvax + sunitinib, intermediate-risk stratum

Reporting group title

Sunitinib-only, intermediate-risk

Reporting group description

Sunitinib-only, intermediate-risk stratum

Reporting group title

Intuvax + sunitinib, total (both strata)

Reporting group description

Intuvax + sunitinib, high and intermediate risk strata combined

Reporting group title

Sunitinib-only, total (both strata)

Reporting group description

Sunitinib-only, high and intermediate risk strata combined

Subject analysis set title

FAS

Subject analysis set type

Full analysis

Subject analysis set description

All patients randomized being evaluable for any high or intermediate stratum related efficacy endpoint.

Subject analysis set title

PPS

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

SAF

Subject analysis set type

Safety analysis

Subject analysis set description

All randomized patients who had at least 1 assessment made at Screening. Safety summaries were performed on the safety set.

Primary: Overall Survival - days (FAS)

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End point title

Overall Survival - days (FAS)

End point description

Due to the amount of censored data, estimates of upper 95% CI could not be reliably determined in all reporting groups (marked by 'NA' below). The medians are presented as 'Number' in the data table. The medians (95% CI) were: Intuvax high-risk: 323 (152, 682) Sunitinib-only high-risk: 282 (39, NA) Intuvax intermediate-risk: 1270 (852, NA) Sunitinib-only intermediate risk: 1099 (234, 1368) Intuvax total (both strata): 1082 (432, NA) Sunitinib-only total (both strata): 770 (234, 1241)

End point type

Primary

End point timeframe

The follow-up time of OS was between 24-1751 days in the high-risk Intuvax group, 39-1372 days in the high-risk sunitinib-only group, 37-1915 days in the intermediate-risk Intuvax group and 56-1677 days in the intermediate-risk sunitinib-only group.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)
Number of subjects analysed	16	8	40	22	56	30
Units: day
number (not applicable)	323	282	1270	1099	1082	770

Overall Survival - High-risk stratum

Comparison groups

Intuvax + sunitinib, high-risk v Sunitinib-only, high-risk

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[1]

P-value

= 0.964

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.978

Confidence interval

level

95%

sides

2-sided

lower limit

0.371

upper limit

2.579

Notes
[1] - Exploratory superiority (non-powered)

Overall Survival - Intermediate-risk stratum

Comparison groups

Intuvax + sunitinib, intermediate-risk v Sunitinib-only, intermediate-risk

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[2]

P-value

= 0.163

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.619

Confidence interval

level

95%

sides

2-sided

lower limit

0.314

upper limit

1.222

Notes
[2] - Exploratory superiority (non-powered)

Overall Survival - Both strata

Comparison groups

Intuvax + sunitinib, total (both strata) v Sunitinib-only, total (both strata)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[3]

P-value

= 0.25

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.732

Confidence interval

level

95%

sides

2-sided

lower limit

0.421

upper limit

1.27

Notes
[3] - Exploratory superiority (non-powered)

Primary: Overall survival - days (PPS)

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End point title

Overall survival - days (PPS)

End point description

Due to the amount of censored data, estimates of upper 95% CI could not be reliably determined in all reporting groups (marked by 'NA' below). The medians are presented as 'Number' in the data table. The medians (95% CI) were: Intuvax high-risk: 352 (240, NA) Sunitinib-only high-risk: 282 (39, NA) Intuvax intermediate-risk: 1745 (911, NA) Sunitinib-only intermediate risk: 1185 (678, NA) Intuvax total (both strata): 1265 (684, NA) Sunitinib-only total (both strata): 1024 (342, 1368)

End point type

Primary

End point timeframe

The follow-up time of OS was between 152-1751 days in the high-risk Intuvax group, 39-1372 days in the high-risk sunitinib-only group, 37-1915 days in the intermediate-risk Intuvax group and 166-1677 days in the intermediate-risk sunitinib-only group.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)
Number of subjects analysed	12	8	34	19	46	27
Units: day
number (not applicable)	352	282	1745	1185	1265	1024

Overall Survival - High-risk stratum

Comparison groups

Sunitinib-only, high-risk v Intuvax + sunitinib, high-risk

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[4]

P-value

= 0.596

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.756

Confidence interval

level

95%

sides

2-sided

lower limit

0.268

upper limit

2.134

Notes
[4] - Exploratory superiority (non-powered)

Overall Survival - Intermediate-risk stratum

Comparison groups

Sunitinib-only, intermediate-risk v Intuvax + sunitinib, intermediate-risk

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

= 0.285

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.661

Confidence interval

level

95%

sides

2-sided

lower limit

0.308

upper limit

1.418

Notes
[5] - Exploratory superiority (non-powered)

Overall Survival - Both strata

Comparison groups

Intuvax + sunitinib, total (both strata) v Sunitinib-only, total (both strata)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[6]

P-value

= 0.24

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.699

Confidence interval

level

95%

sides

2-sided

lower limit

0.378

upper limit

1.29

Notes
[6] - Exploratory superiority (non-powered)

Primary: 18-Months' Overall Survival - Rate (FAS)

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End point title

18-Months' Overall Survival - Rate (FAS)

End point description

End point type

Primary

End point timeframe

At 18 months (544 days).

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)
Number of subjects analysed	16	8	40	22	56	30
Units: Percent
number (not applicable)	30	38	77	76	63	66

Overall survival at 18 months

Comparison groups

Intuvax + sunitinib, high-risk v Sunitinib-only, high-risk v Intuvax + sunitinib, intermediate-risk v Sunitinib-only, intermediate-risk

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[7]

P-value

= 0.05

Method

Logrank

Confidence interval

Notes
[7] - Exploratory superiority (non-powered)

Primary: 18-Months' Overall Survival Rate (PPS)

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End point title

18-Months' Overall Survival Rate (PPS)

End point description

End point type

Primary

End point timeframe

At 18 months (544 days)

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)
Number of subjects analysed	12	8	34	19	46	27
Units: percent
number (not applicable)	31	38	82	84	68	70

Overall survival at 18 months

Comparison groups

Intuvax + sunitinib, high-risk v Sunitinib-only, high-risk v Intuvax + sunitinib, intermediate-risk v Sunitinib-only, intermediate-risk

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[8]

P-value

= 0.05

Method

Logrank

Confidence interval

Notes
[8] - Exploratory superiority (non-powered)

Secondary: Progression-Free Survival

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End point title

Progression-Free Survival ^[9]

End point description

Due to the large amount of censored data, estimates of median and/or a 95% CI could not be reliably determined in all reporting groups (marked by 'NA' below). The median (CI) were: Intuvax high-risk: 254 (43, NA) Sunitinib-only high-risk: NA (NA, NA) Intuvax intermediate-risk: 478 (249, NA) Sunitinib-only intermediate risk: 417 (149, NA) Intuvax total (both strata): 360 (249, NA) Sunitinib-only total (both strata): 337 (149, NA)

End point type

Secondary

End point timeframe

From Sun-Start to PD or death following sunitinib initiation from any cause, whichever occurred first.

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: Due to the large amount of censored data, estimates of median and/or a 95% CI could not be reliably determined in all reporting groups. Those groups have been omitted from the reporting form. However, all estimated values for median and CI are presented in the "Description" of the endpoint, where values that could not be estimated are marked by "NA".

End point values	Intuvax + sunitinib, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)
Number of subjects analysed	13	6	19	46	25
Units: day
number (not applicable)	254	478	417	360	337

No statistical analyses for this end point

Secondary: Objective Response Rate

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End point title

Objective Response Rate

End point description

End point type

Secondary

End point timeframe

From start of sunitinib treatment.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)
Number of subjects analysed	13	6	32	19	45	25
Units: percent
number (not applicable)	38.5	66.7	46.9	42.1	44.4	48.0

No statistical analyses for this end point

Secondary: Best Overall Response

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End point title

Best Overall Response

End point description

End point type

Secondary

End point timeframe

From start of sunitinib treatment.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	FAS
Number of subjects analysed	13	6	32	19	45	25	70
Units: percent
number (not applicable)
Complete Response (CR)	7.7	0	12.5	5.3	11.1	4.0	8.6
Partial Response (PR)	30.8	66.7	34.4	36.8	33.3	44.0	37.1
Progressive Disease (PD)	30.8	0	9.4	10.5	15.6	8.0	12.9
Stable Disease (SD)	15.4	33.3	40.6	36.8	33.3	36.0	34.3
Non-CR/Non-PD	15.4	0	0	5.3	4.4	4.0	4.3
No Disease (ND)	0	0	3.1	5.3	2.2	4.0	2.9

No statistical analyses for this end point

Secondary: Disease Control Rate

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End point title

Disease Control Rate

End point description

End point type

Secondary

End point timeframe

From start of sunitinib treatment.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)
Number of subjects analysed	13	6	32	19	45	25
Units: percent
number (not applicable)	53.8	100.0	87.5	78.9	77.8	84.0

No statistical analyses for this end point

Secondary: Duration of Response

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End point title

Duration of Response

End point description

End point type

Secondary

End point timeframe

From date at which CR or PR was first observed until first occurrence of PD or death.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	FAS
Number of subjects analysed	5	4	15	8	20	12	32
Units: day
median (full range (min-max))	175.0 (101 to 219)	81.5 (42 to 126)	316.0 (1 to 512)	108.0 (1 to 409)	215.0 (1 to 512)	87.0 (1 to 409)	169.5 (1 to 512)

No statistical analyses for this end point

Secondary: Duration of Clinical Benefit

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End point title

Duration of Clinical Benefit

End point description

End point type

Secondary

End point timeframe

From start of DCR until first occurrence of PD or death for patients.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	FAS
Number of subjects analysed	7	6	28	15	35	21	56
Units: day
median (full range (min-max))	212.0 (1 to 434)	60.0 (1 to 206)	323.5 (29 to 512)	295.0 (1 to 451)	219.0 (1 to 512)	133.0 (1 to 451)	211.0 (1 to 512)

No statistical analyses for this end point

Secondary: Duration of Stable Disease

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End point title

Duration of Stable Disease

End point description

End point type

Secondary

End point timeframe

From first date of SD until first occurrence of PD or death.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	FAS
Number of subjects analysed	2	2	13	7	15	9	24
Units: day
median (full range (min-max))	63.5 (1 to 126)	10.5 (1 to 20)	169.0 (29 to 427)	210.0 (50 to 449)	126.0 (1 to 427)	133.0 (1 to 449)	129.5 (1 to 449)

No statistical analyses for this end point

Secondary: Time to Progression

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End point title

Time to Progression

End point description

Due to the large amount of censored data, estimates of median and/or a 95% CI could not be reliably determined in all reporting groups (marked by 'NA' below). The median (CI) were: Intuvax high-risk: 169 (43, NA) Sunitinib-only high-risk: 143 (48, 248) Intuvax intermediate-risk: 388 (213, NA) Sunitinib-only intermediate risk: 417 (93, NA) Intuvax total (both strata): 254 (169, 478) Sunitinib-only total (both strata): 251 (93, 434)

End point type

Secondary

End point timeframe

Time from Sun-Start to date of either PD according to RECIST 1.1 or clinical progression as evaluated by the Investigator.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)
Number of subjects analysed	13	6	33	19	46	25
Units: day
number (not applicable)	169	143	388	417	254	251

No statistical analyses for this end point

Secondary: Number of Infiltrating CD8+ T-Cells

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End point title

Number of Infiltrating CD8+ T-Cells

End point description

Relative number of tumor-infiltrating CD8+ T-cells in the resected primary tumor compared to number of infiltrating CD8+ T-cells in available diagnostic pre-biopsy (sample from either primary tumor or metastasis), was not to be evaluated as described in the protocol due to missing pre-biopsy samples). Instead an automated and validated quantification of percentage of CD8+ tissue in deliniated tumor area was made.

End point type

Secondary

End point timeframe

At resection of primary tumor.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	FAS
Number of subjects analysed	14	7	38	20	52	27	79
Units: percent
median (full range (min-max))	1.0 (0 to 8)	1.1 (0 to 4)	1.2 (0 to 13)	0.8 (0 to 8)	1.1 (0 to 13)	0.8 (0 to 8)	1.1 (0 to 13)

No statistical analyses for this end point

Secondary: Physical Examination

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End point title

Physical Examination

End point description

Results presented for Screening and End of Study visits. All subjects were not evaluated at each visit.

End point type

Secondary

End point timeframe

Assessed at each study visit: Screening, Sun-Start, Vaccination 1-2 (Intuvax group, only) SFU 6W, SFU 12W, SFU 24W, SFU 36W, SFU 48W, SFU 60W and End of Study.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	SAF
Number of subjects analysed	17	8	41	22	58	30	88
Units: percent
number (not applicable)
Abdomen - Baseline Normal	100.0	62.5	95.1	72.7	96.6	70.0	87.5
Abdomen - Baseline Abnormal NCS	0.0	12.5	0.0	4.5	0.0	6.7	2.3
Abdomen - Baseline Abnormal CS	0.0	25.0	4.9	22.7	3.4	23.3	10.2
Abdomen - EoS Normal	88.9	100.0	93.5	93.8	92.5	95.0	93.3
Abdomen - EoS Abnormal NCS	11.1	0.0	6.5	6.3	7.5	5.0	6.7
Abdomen - EoS Abnormal CS	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Cardiovascular - Baseline Normal	100.0	100.0	95.1	86.4	96.6	90.0	94.3
Cardiovascular - Baseline Abnormal NCS	0.0	0.0	0.0	13.6	0.0	10.0	3.4
Cardiovascular - Baseline Abnormal CS	0.0	0.0	4.9	0.0	3.4	0.0	2.3
Cardiovascular - EoS Normal	100.0	75.0	93.5	100.0	95.0	95.0	95.0
Cardiovascular - EoS Abnormal NCS	0.0	0.0	6.5	0.0	5.0	0.0	3.3
Cardiovascular - EoS Abnormal CS	0.0	25.0	0.0	0.0	0.0	5.0	1.7
Ear - Baseline Normal	93.8	100.0	100.0	100.0	98.2	100.0	98.8
Ear - Baseline Abnormal NCS	6.3	0.0	0.0	0.0	1.8	0.0	1.2
Ear - Baseline Abnormal CS	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Ear - EoS Normal	88.9	100.0	96.7	100.0	97.9	100.0	96.6
Ear - EoS Abnormal NCS	0.0	0.0	3.3	0.0	2.6	0.0	1.7
Ear - EoS Abnormal CS	11.1	0.0	0.0	0.0	2.6	0.0	1.7
Eye - Baseline Normal	94.1	100.0	97.6	95.5	96.6	96.7	96.6
Eye - Baseline Abnormal NCS	5.9	0.0	2.4	0.0	3.4	0.0	2.3
Eye - Baseline Abnormal CS	0.0	0.0	0.0	4.5	0.0	3.3	1.1
Eye - EoS Normal	88.9	100.0	96.7	100.0	94.9	100.0	96.6
Eye - EoS Abnormal NCS	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Eye - EoS Abnormal CS	11.1	0.0	3.3	0.0	5.1	0.0	3.4
Lymphatic - Baseline Normal	100.0	100.0	100.0	95.5	100.0	96.7	98.9
Lymphatic - Baseline Abnormal NCS	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Lymphatic - Baseline Abnormal CS	0.0	0.0	0.0	4.5	0.0	3.3	1.1
Lymphatic - EoS Normal	100.0	100.0	100.0	100.0	100.0	100.0	100.0
Lymphatic - EoS Abnormal NCS	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Lymphatic - EoS Abnormal CS	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Neurol./Musculoskeletal - Baseline Normal	100.0	85.7	97.5	94.4	98.2	92.0	96.3
Neurol./Musculoskeletal - Baseline Abnormal NCS	0.0	14.3	0.0	5.6	0.0	8.0	2.4
Neurol./Musculoskeletal - Baseline Abnormal CS	0.0	0.0	2.5	0.0	1.8	0.0	1.2
Neurol./Musculoskeletal - EoS Normal	100.0	100.0	90.0	92.3	92.3	94.1	92.9
Neurol./Musculoskeletal - EoS Abnormal NCS	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Neurol./Musculoskeletal - EoS Abnormal CS	0.0	0.0	10.0	7.7	7.7	5.9	7.1
Nose and Throat - Baseline Normal	94.1	100.0	97.6	100.0	96.6	100.0	97.7
Nose and Throat - Baseline Abnormal NCS	5.9	0.0	2.4	0.0	3.4	0.0	2.3
Nose and Throat - Baseline Abnormal CS	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Nose and Throat - EoS Normal	88.9	100.0	93.3	93.8	92.3	95.0	93.2
Nose and Throat - EoS Abnormal NCS	0.0	0.0	3.3	6.3	2.6	5.0	3.4
Nose and Throat - EoS Abnormal CS	11.1	0.0	3.3	0.0	5.1	0.0	3.4
Other - Baseline Normal	92.3	83.3	100.0	84.6	97.6	84.2	93.3
Other - Baseline Abnormal NCS	7.7	16.7	0.0	15.4	2.4	15.8	6.7
Other - Baseline Abnormal CS	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Other - EoS Normal	85.7	66.7	100.0	91.7	95.8	86.7	92.3
Other - EoS Abnormal NCS	0.0	33.3	0.0	8.3	0.0	13.3	5.1
Other - EoS Abnormal CS	14.3	0.0	0.0	0.0	4.2	0.0	2.6
Respiratory - Baseline Normal	100.0	100.0	92.7	95.5	94.8	96.7	95.5
Respiratory - Baseline Abnormal NCS	0.0	0.0	7.3	0.0	5.2	0.0	3.4
Respiratory - Baseline Abnormal CS	0.0	0.0	0.0	4.5	0.0	3.3	1.1
Respiratory - EoS Normal	100.0	100.0	93.5	93.8	95.0	95.0	95.0
Respiratory - EoS Abnormal NCS	0.0	0.0	6.5	0.0	5.0	0.0	5.0
Respiratory - EoS Abnormal CS	0.0	0.0	0.0	6.3	0.0	5.0	0.0
Skin - Baseline Normal	87.5	87.5	85.4	90.5	86.0	89.7	87.2
Skin - Baseline Abnormal NCS	12.5	12.5	12.2	9.5	12.3	10.3	11.6
Skin - Baseline Abnormal CS	0.0	0.0	2.4	0.0	1.8	0.0	1.2
Skin - EoS Normal	88.9	100.0	86.7	81.3	87.2	85.0	86.4
Skin - EoS Abnormal NCS	11.1	0.0	13.3	12.5	12.8	10.0	11.9
Skin - EoS Abnormal CS	0.0	0.0	0.0	6.3	0.0	5.0	1.7

No statistical analyses for this end point

Secondary: Vital Signs - Weight

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End point title

Vital Signs - Weight

End point description

Results presented for Screening and End of Study visits. All subjects were not evaluated at each visit.

End point type

Secondary

End point timeframe

Assessed at each study visit: Screening, Sun-Start, Vaccination 1-2 (Intuvax group, only) SFU 6W, SFU 12W, SFU 24W, SFU 36W, SFU 48W, SFU 60W and End of Study.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	SAF
Number of subjects analysed	17	8	41	22	58	30	88
Units: kilogram(s)
arithmetic mean (standard deviation)
Screening	77.8 ± 13.8	78.6 ± 8.8	86.4 ± 20.3	84.4 ± 20.1	83.8 ± 18.9	82.9 ± 17.8	83.5 ± 18.4
End of Study	76.7 ± 19.1	80.8 ± 16.4	88.3 ± 25.5	87.9 ± 23.0	85.4 ± 24.4	85.9 ± 21.3	85.6 ± 23.1

No statistical analyses for this end point

Secondary: Vital Signs - Blood Pressure

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End point title

Vital Signs - Blood Pressure

End point description

Results presented for Screening and End of Study visits. All subjects were not evaluated at each visit.

End point type

Secondary

End point timeframe

Assessed at each study visit: Screening, Sun-Start, Vaccination 1-2 (Intuvax group, only) SFU 6W, SFU 12W, SFU 24W, SFU 36W, SFU 48W, SFU 60W and End of Study.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	SAF
Number of subjects analysed	17	8	41	22	58	30	88
Units: mmHg
arithmetic mean (standard deviation)
Systolic Blood Pressure - Baseline	131.0 ± 13.8	132.1 ± 17.3	139.2 ± 18.0	141.7 ± 20.7	136.7 ± 17.1	139.1 ± 20.1	137.5 ± 18.1
Systolic Blood Pressure - End of Study	140.4 ± 22.7	126.8 ± 13.8	133.0 ± 15.6	140.4 ± 12.8	134.8 ± 17.5	136.8 ± 14.1	135.5 ± 16.3
Diastolic Blood Pressure - Baseline	74.2 ± 9.8	74.3 ± 10.7	81.0 ± 8.7	77.2 ± 10.3	78.9 ± 9.5	76.4 ± 10.3	78.0 ± 9.8
Diastolic Blood Pressure - End of Study	79.9 ± 9.4	77.5 ± 13.6	81.0 ± 11.6	79.8 ± 12.4	80.8 ± 11.0	79.2 ± 12.4	80.2 ± 11.5

No statistical analyses for this end point

Secondary: Vital Signs - Heart Rate

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End point title

Vital Signs - Heart Rate

End point description

Results presented for Screening and End of Study visits. All subjects were not evaluated at each visit.

End point type

Secondary

End point timeframe

Assessed at each study visit: Screening, Sun-Start, Vaccination 1-2 (Intuvax group, only) SFU 6W, SFU 12W, SFU 24W, SFU 36W, SFU 48W, SFU 60W and End of Study.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	SAF
Number of subjects analysed	17	8	41	22	58	30	88
Units: beats/min
arithmetic mean (standard deviation)
Screening	81.2 ± 12.5	89.0 ± 12.9	76.3 ± 11.4	80.1 ± 13.5	77.8 ± 11.9	82.5 ± 13.7	79.4 ± 12.7
End of Study	85.9 ± 10.2	78.2 ± 20.0	76.2 ± 14.3	69.9 ± 8.9	78.3 ± 14.0	72.3 ± 13.0	76.1 ± 13.8

No statistical analyses for this end point

Secondary: Vital Signs - Temperature

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End point title

Vital Signs - Temperature

End point description

Results presented for Screening and End of Study visits. All subjects were not evaluated at each visit.

End point type

Secondary

End point timeframe

Assessed at each study visit: Screening, Sun-Start, Vaccination 1-2 (Intuvax group, only) SFU 6W, SFU 12W, SFU 24W, SFU 36W, SFU 48W, SFU 60W and End of Study.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	SAF
Number of subjects analysed	17	8	41	22	58	30	88
Units: degrees Celcius
arithmetic mean (standard deviation)
Screening	36.6 ± 0.7	36.9 ± 0.4	36.6 ± 0.5	36.5 ± 0.5	36.6 ± 0.6	36.6 ± 0.5	36.6 ± 0.6
End of Study	36.6 ± 0.4	36.7 ± 0.8	36.4 ± 0.6	36.4 ± 0.4	36.5 ± 0.6	36.5 ± 0.5	36.5 ± 0.5

No statistical analyses for this end point

Secondary: Laboratory Evaluation - Hematology

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End point title

Laboratory Evaluation - Hematology

End point description

Results presented for Screening and End of Study visits. All subjects were not evaluated at each visit.

End point type

Secondary

End point timeframe

Assessed at each study visit: Screening, Sun-Start, Vaccination 1-2 (Intuvax group, only) SFU 6W, SFU 12W, SFU 24W, SFU 36W, SFU 48W, SFU 60W and End of Study.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	SAF
Number of subjects analysed	17	8	41	22	58	30	88
Units: percent
number (not applicable)
Basophils - Baseline Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Basophils - Baseline Normal	100.0	100.0	100.0	100.0	100.0	100.0	100.0
Basophils - Baseline High	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Basophils - EoS Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Basophils - EoS Normal	100.0	100.0	100.0	100.0	100.0	100.0	100.0
Basophils - EoS High	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Eosinophils - Baseline Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Eosinophils - Baseline Normal	93.8	100.0	92.5	100.0	92.9	100.0	95.3
Eosinophils - Baseline High	6.3	0.0	7.5	0.0	7.1	0.0	4.7
Eosinophils - EoS Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Eosinophils - EoS Normal	100.0	100.0	100.0	100.0	100.0	100.0	100.0
Eosinophils - EoS High	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Hemoglobin - Baseline Low	100.0	85.7	35.0	50.0	53.6	58.6	55.3
Hemoglobin - Baseline Normal	0.0	14.3	57.5	50.0	41.1	41.4	41.2
Hemoglobin - Baseline High	0.0	0.0	7.5	0.0	5.4	0.0	3.5
Hemoglobin - EoS Low	60.0	50.0	39.3	50.0	44.7	50.0	46.7
Hemoglobin - EoS Normal	40.0	50.0	60.7	50.0	55.3	50.0	53.3
Hemoglobin - EoS High	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Lymphocytes - Baseline Low	12.5	0.0	12.5	18.2	12.5	13.8	12.9
Lymphocytes - Baseline Normal	87.5	100.0	82.5	81.8	83.9	86.2	84.7
Lymphocytes - Baseline High	0.0	0.0	5.0	0.0	3.6	0.0	2.4
Lymphocytes - EoS Low	40.0	33.3	21.4	6.3	26.3	13.6	21.7
Lymphocytes - EoS Normal	50.0	50.0	78.6	93.8	71.1	81.8	75.0
Lymphocytes - EoS High	10.0	16.7	0.0	0.0	2.6	4.5	3.3
Monocytes - Baseline Low	0.0	0.0	2.5	4.5	1.8	3.4	2.4
Monocytes - Baseline Normal	50.0	85.7	90.0	86.4	78.6	86.2	81.2
Monocytes - Baseline High	50.0	14.3	7.5	9.1	19.6	10.3	16.5
Monocytes - EoS Low	0.0	16.7	17.9	0.0	13.2	4.5	10.0
Monocytes - EoS Normal	90.0	66.7	75.0	93.8	78.9	86.4	81.7
Monocytes - EoS High	10.0	16.7	7.1	6.3	7.9	9.1	8.3
Platelets - Baseline Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Platelets - Baseline Normal	37.5	28.6	100.0	100.0	82.1	82.8	82.4
Platelets - Baseline High	62.5	71.4	0.0	0.0	17.9	17.2	17.6
Platelets - EoS Low	0.0	0.0	10.7	0.0	7.9	0.0	5.0
Platelets - EoS Normal	100.0	83.3	82.1	100.0	86.8	95.5	90.0
Platelets - EoS High	0.0	16.7	7.1	0.0	5.3	4.5	5.0
Neutrophils - Baseline Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Neutrophils - Baseline Normal	68.8	57.1	95.0	90.9	87.5	82.8	85.9
Neutrophils - Baseline High	31.3	42.9	5.0	9.1	12.5	17.2	14.1
Neutrophils - EoS Low	0.0	16.7	32.1	12.5	23.7	13.6	20.0
Neutrophils - EoS Normal	100.0	66.7	64.3	87.5	73.7	81.8	76.7
Neutrophils - EoS High	0.0	16.7	3.6	0.0	2.6	4.5	3.3
Erythrocytes - Baseline Low	37.5	42.9	2.5	13.6	12.5	20.7	15.3
Erythrocytes - Baseline Normal	62.5	57.1	90.0	86.4	82.1	79.3	81.2
Erythrocytes - Baseline High	0.0	0.0	7.5	0.0	5.4	0.0	3.5
Erythrocytes - EoS Low	70.0	50.0	60.7	56.3	63.2	54.5	60.0
Erythrocytes - EoS Normal	30.0	50.0	39.3	43.8	36.8	45.5	40.0
Erythrocytes - EoS High	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Leukocytes - Baseline Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Leukocytes - Baseline Normal	68.8	57.1	100.0	95.5	91.1	86.2	89.4
Leukocytes - Baseline High	31.3	42.9	0.0	4.5	8.9	13.8	10.6
Leukocytes - EoS Low	0.0	16.7	35.7	12.5	26.3	13.6	21.7
Leukocytes - EoS Normal	100.0	83.3	60.7	87.5	71.1	86.4	76.7
Leukocytes - EoS High	0.0	0.0	3.6	0.0	2.6	0.0	1.7

No statistical analyses for this end point

Secondary: Laboratory Evaluation - Clinical Chemistry

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End point title

Laboratory Evaluation - Clinical Chemistry

End point description

Samples were evaluated for albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, calcium, creatinine, c-reactive protein, glomerular filtration rate, gamma glutamyl transferase, glucose, potassium, lactate dehydrogenase, sodium, thyroxine free, thyrotropin. Out of these, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin are presented as these parameters are known AEs for sunitinib treatment, and calcium and creatinine are presented as they are related to the diagnosis.

End point type

Secondary

End point timeframe

Assessed at each study visit: Screening, Sun-Start, Vaccination 1-2 (Intuvax group, only) SFU 6W, SFU 12W, SFU 24W, SFU 36W, SFU 48W, SFU 60W and End of Study.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	SAF
Number of subjects analysed	17	8	41	22	58	30	88
Units: percent
number (not applicable)
ALT - Baseline Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
ALT - Baseline Normal	88.2	87.5	97.6	90.5	94.8	89.7	93.1
ALT - Baseline High	11.8	12.5	2.4	9.5	5.2	10.3	6.9
ALT - EoS Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
ALT - EoS Normal	90.0	83.3	96.4	86.7	94.7	85.7	91.5
ALT - EoS High	10.0	16.7	3.6	13.3	5.3	14.3	8.5
AST - Baseline Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
AST - Baseline Normal	94.1	100.0	97.6	95.5	96.6	96.7	96.6
AST - Baseline High	5.9	0.0	2.4	4.5	3.4	3.3	3.4
AST - EoS Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
AST - EoS Normal	70.0	100.0	100.0	86.7	92.1	90.5	91.5
AST - EoS High	30.0	0.0	0.0	13.3	7.9	9.5	8.5
Bilirubin - Baseline Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Bilirubin - Baseline Normal	100.0	100.0	100.0	100.0	100.0	100.0	100.0
Bilirubin - Baseline High	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Bilirubin - EoS Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Bilirubin - EoS Normal	90.0	100.0	100.0	100.0	97.4	100.0	98.3
Bilirubin - EoS High	10.0	0.0	0.0	0.0	2.6	0.0	1.7
Calcium - Baseline Low	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Calcium - Baseline Normal	52.9	50.0	92.7	100.0	81.0	86.7	83.0
Calcium - Baseline High	47.1	50.0	7.3	0.0	19.0	13.3	17.0
Calcium - EoS Low	0.0	0.0	11.1	6.3	8.1	4.5	6.8
Calcium - EoS Normal	90.0	100.0	85.2	93.8	86.5	95.5	89.8
Calcium - EoS High	10.0	0.0	3.7	0.0	5.4	0.0	3.4
Creatinine - Baseline Low	0.0	12.5	2.4	9.1	1.7	10.0	4.5
Creatinine - Baseline Normal	82.4	87.5	85.4	72.7	84.5	76.7	81.8
Creatinine - Baseline High	17.6	0.0	12.2	18.2	13.8	13.3	13.6
Creatinine - EoS Low	10.0	0.0	3.6	0.0	5.3	0.0	3.3
Creatinine - EoS Normal	40.0	33.3	35.7	37.5	36.8	36.4	36.7
Creatinine - EoS High	50.0	66.7	60.7	62.5	57.9	63.6	60.0

No statistical analyses for this end point

Secondary: Laboratory Evaluation - Coagulation

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End point title

Laboratory Evaluation - Coagulation

End point description

Results presented for Screening and End of Study (Final Visit). All subjects were not evaluated at each visit.

End point type

Secondary

End point timeframe

Assessed at Screening, Vaccination 1-2 (Intuvax group, only), Surgery-Nephrectomy and End of Study (Final Visit).

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	SAF
Number of subjects analysed	17	8	41	22	58	30	88
Units: percent
number (not applicable)
APTT - Baseline Low	0.0	20.0	2.8	10.0	1.9	12.0	5.2
APTT - Baseline Normal	75.0	60.0	77.8	75.0	76.9	72.0	75.3
APTT - Baseline High	25.0	20.0	19.4	15.0	21.2	16.0	19.5
APTT - EoS Low	0.0	20.0	8.3	10.0	5.8	12.0	7.8
APTT - EoS Normal	68.8	60.0	77.8	75.0	75.0	72.0	74.0
APTT - EoS High	31.3	20.0	13.9	15.0	19.2	16.0	18.2
PT-INR - Baseline Low	0.0	0.0	0.0	4.8	0.0	3.8	1.5
PT-INR - Baseline Normal	83.3	80.0	92.9	76.2	90.0	76.9	84.8
PT-INR - Baseline High	16.7	20.0	7.1	19.0	10.0	19.2	13.6
PT-INR - EoS Low	0.0	0.0	3.2	0.0	2.3	0.0	1.4
PT-INR - EoS Normal	58.3	100.0	87.1	90.5	79.1	92.3	84.1
PT-INR - EoS High	41.7	0.0	9.7	9.5	18.6	7.7	14.5

No statistical analyses for this end point

Other pre-specified: ECOG Performance Status

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End point title

ECOG Performance Status

End point description

The proportion of patients with improvement since the Screening is presented for each visit. All subjects were not evaluated at each visit.

End point type

Other pre-specified

End point timeframe

Assessed at each study visit: Screening, Sun-Start, SFU 6W, SFU 12W, SFU 24W, SFU 36W, SFU 48W, SFU 60W and End of Study.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	FAS
Number of subjects analysed	16	8	40	22	56	30	86
Units: percent
number (not applicable)
Sun-Start	30.8	16.7	19.4	27.8	22.7	25.0	23.5
SFU 6 Weeks	27.3	0.0	25.0	29.4	25.6	23.8	25.0
SFU 12 Weeks	30.0	0.0	18.5	28.6	21.6	22.2	21.8
SFU 24 Weeks	12.5	0.0	13.0	30.8	12.9	28.6	17.8
SFU 36 Weeks	40.0	0.0	10.5	27.3	16.7	27.3	20.0
SFU 48 Weeks	0.0	0.0	15.8	27.3	14.3	27.3	18.8
SFU 60 Weeks	0.0	0.0	12.5	37.5	11.1	37.5	19.2
End of Study	50.0	33.3	35.5	41.2	39.5	39.1	39.4

No statistical analyses for this end point

Other pre-specified: Quality of Life - EORTC QLQ-C30

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End point title

Quality of Life - EORTC QLQ-C30

End point description

The proportion of patients with improvementat at End of Study compared to Screening is presented. All subjects were not evaluated at each visit.

End point type

Other pre-specified

End point timeframe

Assessed at each study visit: Screening, Sun-Start, SFU 6W, SFU 12W, SFU 24W, SFU 36W, SFU 48W, SFU 60W and End of Study.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	FAS
Number of subjects analysed	16	8	40	22	39	22	86
Units: percent
number (not applicable)
Cognitive functioning	8.3	40.0	11.1	35.3	10.3	36.4	19.7
Emotional functioning	33.3	60.0	59.3	52.9	51.3	54.5	52.5
Global Health Status	41.7	20.0	22.2	58.8	28.2	50.0	36.1
Physical functioning	0.0	0.0	18.5	23.5	12.8	18.2	14.8
Role functioning	18.2	20.0	7.4	35.3	10.5	31.8	18.3
Social functioning	25.0	20.0	7.4	29.4	12.8	27.3	18.0

No statistical analyses for this end point

Other pre-specified: Correlation between MHC mismatch and infiltrating CD8+ T cells

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End point title

Correlation between MHC mismatch and infiltrating CD8+ T cells ^[10]

End point description

End point type

Other pre-specified

End point timeframe

HLA type collected at Screening and number of infiltrating CD8+ T cells evaluated at nephrectomy.

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: This endpoint is only applicable to patients in the Intuvax group.

End point values	Intuvax + sunitinib, high-risk	Intuvax + sunitinib, intermediate-risk	Intuvax + sunitinib, total (both strata)
Number of subjects analysed	16	40	56
Units: unitless
number (not applicable)
Spearman correlation	0.0829	-0.0242	0.0372

No statistical analyses for this end point

Other pre-specified: Auto- and allo-immunization

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End point title

Auto- and allo-immunization ^[11]

End point description

Proportion of patients positive for antibodies at start of sunitinib treatment. For alloimmunization (HLA class I/II), only patients who developed antibodies de novo are presented.

End point type

Other pre-specified

End point timeframe

From Vaccination visit 1 to start of sunitinib treatment

Notes
[11] - 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: This endpoint is only applicable to patients in the Intuvax group.

End point values	Intuvax + sunitinib, high-risk	Intuvax + sunitinib, intermediate-risk	Intuvax + sunitinib, total (both strata)
Number of subjects analysed	16	40	56
Units: percent
number (not applicable)
<1:160 antinuclear antibodies	100.0	100.0	100.0
Antimitochondrial antibodies	8.3	0.0	2.5
HLA class I/II	66.7	57.1	60.0
Liver kidney microsomal type 1	0.0	0.0	0.0

No statistical analyses for this end point

Other pre-specified: Time to Treatment Failure

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End point title

Time to Treatment Failure ^[12]

End point description

Due to the large amount of censored data, estimates of median and/or a 95% CI could not be reliably determined in all reporting groups (marked by 'NA' below). The median (CI) were: Intuvax high-risk: 403 (201, NA) Sunitinib-only high-risk: 302 (271, 333) Intuvax intermediate-risk: NA (NA, NA) Sunitinib-only intermediate risk: NA (NA, NA) Intuvax total (both strata): NA (NA, NA) Sunitinib-only total (both strata): NA (NA, NA)

End point type

Other pre-specified

End point timeframe

Following PD or clinical progression.

Notes
[12] - 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: Due to the large amount of censored data, estimates of median and/or a 95% CI could not be reliably determined in all reporting groups. Those groups have been omitted from the reporting form. However, all estimated values for median and CI are presented in the "Description" of the endpoint, where values that could not be estimated are marked by "NA".

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk
Number of subjects analysed	16	8
Units: day
number (not applicable)	403	302

No statistical analyses for this end point

Other pre-specified: Tumor Response from Screening to Sun-Start

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End point title

Tumor Response from Screening to Sun-Start

End point description

End point type

Other pre-specified

End point timeframe

From Screening to start of sunitinib treatment.

End point values	Intuvax + sunitinib, high-risk	Sunitinib-only, high-risk	Intuvax + sunitinib, intermediate-risk	Sunitinib-only, intermediate-risk	Intuvax + sunitinib, total (both strata)	Sunitinib-only, total (both strata)	FAS
Number of subjects analysed	12	5	29	16	41	21	86
Units: percent
number (not applicable)
Complete Response (CR)	0.0	0.0	0.0	6.3	0.0	4.8	1.6
Partial Response (PR)	0.0	0.0	3.4	0.0	2.4	0.0	1.6
Progressive Disease (PD)	66.7	100.0	62.1	43.8	63.4	57.1	61.3
Stable Disease (SD)	25.0	0.0	20.7	43.8	22.0	33.3	25.8
Non-CR/Non-PD	8.3	0.0	0.0	6.3	2.4	4.8	3.2
No Disease (ND)	0.0	0.0	13.8	0.0	9.8	0.0	6.5

No statistical analyses for this end point

Other pre-specified: Exploratory Cox Model Analyses

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End point title

Exploratory Cox Model Analyses

End point description

Comparison between treatment groups: Intuvax group compared to sunitinib-only group.

End point type

Other pre-specified

End point timeframe

Number of tumor-infiltrating CD8+ T-cells evaluated at nephrectomy. TNM staging assessed at baseline. Sunitinib dose density assessed during treatment period. Survival (overall survival [OS], progression-free survival [PFS]) evaluated throughout study.

End point values	FAS
Number of subjects analysed	86
Units: unitless p-value
number (not applicable)
CD8+ vs. OS (by treatment group)	0.6194
CD8+ vs. OS (reduced model)	0.2559
CD8+ vs. PFS (by treatment group)	0.8095
CD8+ vs. PFS (reduced model)	0.2325
N1 vs. OS (by treatment group)	0.4178
N1 vs. OS (reduced model)	0.3017
N1 vs. PFS (by treatment group)	0.6060
N1 vs. PFS (reduced model)	0.4733
T3a vs. OS (by treatment group)	0.4707
T3a vs. OS (reduced model)	0.3636
T3a vs. PFS (by treatment group)	0.9023
T3a vs. PFS (reduced model)	0.8381
Dose density vs. OS (by treatment group)	0.2519
Dose density vs. OS (reduced model)	0.0013
Dose density vs. PFS (by treatment group)	0.0445
Dose density vs. PFS (reduced model)	0.6034

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From first dose to last follow-up.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

Intuvax+sunitinib group (Intuvax)

Reporting group description

Intuvax, high and intermediate risk strata combined. "Occurrences causally related to treatment" and "deaths causally related to treatment" is reporting AEs related to Intuvax.

Reporting group title

Intuvax+sunitinib group (sunitinib)

Reporting group description

Intuvax, high and intermediate risk strata combined. "Occurrences causally related to treatment" and "deaths causally related to treatment" is reporting AEs related to sunitinib.

Reporting group title

Sunitinib-only group

Reporting group description

Sunitinib-only, high and intermediate risk strata combined.

Serious adverse events	Intuvax+sunitinib group (Intuvax)	Intuvax+sunitinib group (sunitinib)	Sunitinib-only group
Total subjects affected by serious adverse events
subjects affected / exposed	27 / 58 (46.55%)	27 / 58 (46.55%)	17 / 30 (56.67%)
number of deaths (all causes)	7	7	6
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metastatic bone disease prophylaxis
Additional description: Recorded as "Metastatic pain"
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thyroid cancer
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	2 / 30 (6.67%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 1
Death
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0
General physical health deterioration
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 3	1 / 3	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 2	0 / 0
Multi-organ disorder
Additional description: Listed as "multi-organ failure"
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Pyrexia
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Uterine haemorrhage
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Confusional state
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Blood thyroid stimulating hormone increased
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General physical condition abnormal
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0
Injury, poisoning and procedural complications
Humerus fracture
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pelvic fracture
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	2 / 58 (3.45%)	2 / 58 (3.45%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 2	0 / 0
Procedural pain
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound evisceration
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Left ventricular dysfunction
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Aphasia
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Brain oedema
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hemiparesis
subjects affected / exposed	1 / 58 (1.72%)	0 / 58 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Paresis
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sciatica
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal cord compression
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 2	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 1	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	2 / 30 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal inflammation
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	2 / 58 (3.45%)	2 / 58 (3.45%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 2	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bone pain
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pathological fracture
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	2 / 30 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastrointestinal infection
subjects affected / exposed	1 / 58 (1.72%)	0 / 58 (0.00%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lymphangitis
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	2 / 30 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Post procedural infection
subjects affected / exposed	2 / 58 (3.45%)	2 / 58 (3.45%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1
Urinary tract infection
subjects affected / exposed	2 / 58 (3.45%)	2 / 58 (3.45%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal viral infection
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	2 / 58 (3.45%)	2 / 58 (3.45%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 2	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	2 / 30 (6.67%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Intuvax+sunitinib group (Intuvax)	Intuvax+sunitinib group (sunitinib)	Sunitinib-only group
Total subjects affected by non serious adverse events
subjects affected / exposed	54 / 58 (93.10%)	54 / 58 (93.10%)	27 / 30 (90.00%)
Vascular disorders
Hypertension
subjects affected / exposed	12 / 58 (20.69%)	12 / 58 (20.69%)	6 / 30 (20.00%)
occurrences all number	18	18	6
Hypotension
subjects affected / exposed	4 / 58 (6.90%)	4 / 58 (6.90%)	1 / 30 (3.33%)
occurrences all number	5	5	1
General disorders and administration site conditions
Asthenia
subjects affected / exposed	11 / 58 (18.97%)	11 / 58 (18.97%)	5 / 30 (16.67%)
occurrences all number	19	19	5
Fatigue
subjects affected / exposed	14 / 58 (24.14%)	14 / 58 (24.14%)	8 / 30 (26.67%)
occurrences all number	14	14	11
General physical health deterioration
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	1 / 30 (3.33%)
occurrences all number	3	3	1
Mucosal inflammation
subjects affected / exposed	6 / 58 (10.34%)	6 / 58 (10.34%)	1 / 30 (3.33%)
occurrences all number	10	10	1
Pain
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	0 / 30 (0.00%)
occurrences all number	3	3	0
Pyrexia
subjects affected / exposed	11 / 58 (18.97%)	11 / 58 (18.97%)	4 / 30 (13.33%)
occurrences all number	18	18	6
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	4 / 58 (6.90%)	4 / 58 (6.90%)	1 / 30 (3.33%)
occurrences all number	4	4	1
Dyspnoea
subjects affected / exposed	4 / 58 (6.90%)	4 / 58 (6.90%)	2 / 30 (6.67%)
occurrences all number	4	4	2
Epistaxis
subjects affected / exposed	5 / 58 (8.62%)	5 / 58 (8.62%)	2 / 30 (6.67%)
occurrences all number	8	8	2
Psychiatric disorders
Anxiety
subjects affected / exposed	5 / 58 (8.62%)	5 / 58 (8.62%)	0 / 30 (0.00%)
occurrences all number	6	6	0
Investigations
Blood creatinine increased
subjects affected / exposed	6 / 58 (10.34%)	6 / 58 (10.34%)	4 / 30 (13.33%)
occurrences all number	9	9	5
Gamma-glutamyltransferase increased
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	0 / 30 (0.00%)
occurrences all number	3	3	0
Glomerular filtration rate decreased
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	1 / 30 (3.33%)
occurrences all number	3	3	1
Neutrophil count decreased
subjects affected / exposed	4 / 58 (6.90%)	4 / 58 (6.90%)	4 / 30 (13.33%)
occurrences all number	5	5	4
Platelet count decreased
subjects affected / exposed	2 / 58 (3.45%)	2 / 58 (3.45%)	3 / 30 (10.00%)
occurrences all number	3	3	4
Injury, poisoning and procedural complications
Procedural pain
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	3 / 30 (10.00%)
occurrences all number	3	3	3
Nervous system disorders
Dizziness
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	3 / 30 (10.00%)
occurrences all number	3	3	4
Dysgeusia
subjects affected / exposed	9 / 58 (15.52%)	9 / 58 (15.52%)	5 / 30 (16.67%)
occurrences all number	14	14	7
Headache
subjects affected / exposed	7 / 58 (12.07%)	7 / 58 (12.07%)	1 / 30 (3.33%)
occurrences all number	8	8	1
Paresis
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	2 / 30 (6.67%)
occurrences all number	1	1	2
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	14 / 58 (24.14%)	14 / 58 (24.14%)	4 / 30 (13.33%)
occurrences all number	19	19	4
Neutropenia
subjects affected / exposed	4 / 58 (6.90%)	4 / 58 (6.90%)	1 / 30 (3.33%)
occurrences all number	5	5	1
Thrombocytopenia
subjects affected / exposed	5 / 58 (8.62%)	5 / 58 (8.62%)	0 / 30 (0.00%)
occurrences all number	7	7	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	2 / 30 (6.67%)
occurrences all number	3	3	2
Abdominal pain upper
subjects affected / exposed	4 / 58 (6.90%)	4 / 58 (6.90%)	3 / 30 (10.00%)
occurrences all number	4	4	3
Constipation
subjects affected / exposed	7 / 58 (12.07%)	7 / 58 (12.07%)	2 / 30 (6.67%)
occurrences all number	7	7	2
Diarrhoea
subjects affected / exposed	14 / 58 (24.14%)	14 / 58 (24.14%)	7 / 30 (23.33%)
occurrences all number	23	23	13
Gastritis
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	0 / 30 (0.00%)
occurrences all number	3	3	0
Gastrooesophageal reflux disease
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	1 / 30 (3.33%)
occurrences all number	8	8	1
Nausea
subjects affected / exposed	14 / 58 (24.14%)	14 / 58 (24.14%)	7 / 30 (23.33%)
occurrences all number	21	21	8
Oral pain
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	3 / 30 (10.00%)
occurrences all number	3	3	3
Stomatitis
subjects affected / exposed	6 / 58 (10.34%)	6 / 58 (10.34%)	6 / 30 (20.00%)
occurrences all number	8	8	10
Vomiting
subjects affected / exposed	14 / 58 (24.14%)	14 / 58 (24.14%)	0 / 30 (0.00%)
occurrences all number	21	21	0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	0	2
Skin and subcutaneous tissue disorders
Dry skin
subjects affected / exposed	4 / 58 (6.90%)	4 / 58 (6.90%)	2 / 30 (6.67%)
occurrences all number	4	4	2
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	7 / 58 (12.07%)	7 / 58 (12.07%)	3 / 30 (10.00%)
occurrences all number	8	8	3
Pruritus
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	0 / 30 (0.00%)
occurrences all number	4	4	0
Rash
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	1 / 30 (3.33%)
occurrences all number	4	4	1
Renal and urinary disorders
Haematuria
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	0 / 30 (0.00%)
occurrences all number	3	3	0
Renal failure acute
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	2 / 30 (6.67%)
occurrences all number	1	1	2
Renal impairment
subjects affected / exposed	2 / 58 (3.45%)	2 / 58 (3.45%)	2 / 30 (6.67%)
occurrences all number	3	3	2
Renal failure chronic
subjects affected / exposed	2 / 58 (3.45%)	2 / 58 (3.45%)	2 / 30 (6.67%)
occurrences all number	2	2	2
Endocrine disorders
Hypothyroidism
subjects affected / exposed	8 / 58 (13.79%)	8 / 58 (13.79%)	3 / 30 (10.00%)
occurrences all number	9	9	3
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	5 / 58 (8.62%)	5 / 58 (8.62%)	3 / 30 (10.00%)
occurrences all number	5	5	3
Back pain
subjects affected / exposed	10 / 58 (17.24%)	10 / 58 (17.24%)	3 / 30 (10.00%)
occurrences all number	13	13	3
Musculoskeletal pain
subjects affected / exposed	4 / 58 (6.90%)	4 / 58 (6.90%)	0 / 30 (0.00%)
occurrences all number	4	4	0
Neck pain
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	0	2
Pain in extremity
subjects affected / exposed	5 / 58 (8.62%)	5 / 58 (8.62%)	2 / 30 (6.67%)
occurrences all number	7	7	2
Pathological fracture
subjects affected / exposed	0 / 58 (0.00%)	0 / 58 (0.00%)	3 / 30 (10.00%)
occurrences all number	0	0	3
Infections and infestations
Pneumonia
subjects affected / exposed	1 / 58 (1.72%)	1 / 58 (1.72%)	2 / 30 (6.67%)
occurrences all number	1	1	2
Urinary tract infection
subjects affected / exposed	6 / 58 (10.34%)	6 / 58 (10.34%)	2 / 30 (6.67%)
occurrences all number	6	6	2
Nasopharyngitis
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	1 / 30 (3.33%)
occurrences all number	3	3	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	10 / 58 (17.24%)	10 / 58 (17.24%)	5 / 30 (16.67%)
occurrences all number	12	12	5
Hypercalcaemia
subjects affected / exposed	4 / 58 (6.90%)	4 / 58 (6.90%)	2 / 30 (6.67%)
occurrences all number	6	6	3
Hyperkalaemia
subjects affected / exposed	3 / 58 (5.17%)	3 / 58 (5.17%)	0 / 30 (0.00%)
occurrences all number	3	3	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

26 May 2015

The primary objective/endpoint was updated. The previous secondary objective on 18 months’ survival rate in intermediate-risk patients was included as a primary objective to include intermediate-risk patients in the primary objective of the study. Clarification of exclusion criteria regarding hypertension, cardiomyopathy, and diabetes mellitus (No. 4 and 9 in CSP ver 2.0). Patients with uncontrolled diabetes mellitus are excluded from the study. Cardiomyopathy was moved to list of exclusion criteria. Clarification of exploratory objectives/endpoints. Routine histology was removed as an exploratory endpoint. CD163 will be analyzed and not CD133. Section on withdrawals was updated to include more details. Patients who discontinued treatment with Intuvax and/or patients whose condition deteriorated much more quickly than expected after enrolment so that the planned nephrectomy could not be performed was not considered withdrawn from study unless there were other reasons for withdrawal. Discontinuation of Intuvax/Sunitinib for safety reasons did not result in withdrawal from study unless there are other reasons for withdrawal. Progressive disease after initiation of Sunitinib, need for change of systemic anti-cancer treatment, and histological findings that does not confirm RCC diagnosis were added to the withdrawal from study criteria. Collection of survival data after EoS visit was added. An optional confirmatory biopsy assessment of the RCC diagnosis for patients randomized to vaccination was included. Information on the IMP to reflect the updated IMPD was included. Study period and contact information were updated. Language and typographic errors were corrected. Minor adjustments and clarifications were performed.

04 Dec 2015

Initiation of sunitinib for the intermediate-risk population was updated to between five (5) and eight (8) weeks post-nephrectomy (as for the high-risk population), thus not demanding tumor progression after nephrectomy before starting sunitinib treatment. This change in study design was performed in order to adapt the study treatment to current treatment recommendations in the majority of participating countries. Also, during the initial stage of the IND process FDA has come back to Immunicum AB with strong recommendations to perform this update on intermediate risk patients as US is one of the countries where this start-point after nephrectomy (not demanding tumor progression after nephrectomy before starting sunitinib treatment) forms part of the current standard of care. This approach is in line with current ESMO and NCCN guidelines. As a result, the secondary objectives/endpoints for the intermediate-risk patient population with baseline previously defined at Screening or sunitinib start visit, i.e. when PD has been confirmed, were removed. Inclusion criterion 1 was updated to specify a minimum size of metastases and to clarify that histological/cytological verification of diagnosis is optional. Update of inclusion criterion and concomitant therapy relating to Hemoglobin. The lower limit of hemoglobin (Hb) at Screening and acceptance of blood transfusion or epoetin alpha treatment were changed. Liver function assessments were changed. Child-Pugh assessment has been replaced with assessments of Serum-Bilirubin, Aspartate Aminotransferase (ASAT), and Alanine Aminotransferase (ALAT). PT-INR analysis is no longer needed post nephrectomy. Clarification regarding pregnancy precautions to accommodate potential withdrawals and comply with restrictions in SmPC. Participating patients have to agree to use contraception from Screening until 90 days after last dose of Intuvax and/or until completed sunitinib treatment whichever occurs later. [more info available]

11 Jul 2016

Substantial amendment 3 was submitted to FDA (US) only but was never implemented. All changes made in substantial amendment 3 are described in substantial amendment 4.

26 Oct 2016

The primary, secondary and exploratory objectives and endpoints were updated: Previous evaluation of OS from randomization in vaccinated vs. non-vaccinated high-risk mRCC patients has been extended to also include evaluation of OS in intermediate-risk patients and in total. Previous evaluation of 18-month survival rate from randomization in vaccinated vs. non-vaccinated intermediate-risk mRCC patients has been extended to also include evaluation of 18-month survival rate in high-risk patients and in total. Previous secondary objective / endpoint evaluation of “response” has been updated to also include duration of response and duration of SD. Evaluation of TTP has been added as a new secondary objective/endpoint. To confirm mode of action of Intuvax, previous secondary objective/endpoint on evaluation of CD8+ T-cells has been updated to include analysis of CD8+ T-cells from diagnostic pre-biopsies when available and to compare the results with the tumor biopsies collected at nephrectomy. An additional exploratory endpoint has been included in order to further evaluate correlation and degree of MHC mismatch between vaccine donor cells and the treated patient. TTF in patients scheduled for second line systemic therapy has been added to the list of exploratory objectives/endpoints. The countries, number of sites and study period were updated. Inclusion and exclusion criteria were changed: Clarification of inclusion criterion 1 that US patients must have clear-cell renal tumor histology. As non clear cell carcinomas were not excluded in Europe, Immunicum AB will monitor the clear cell to non clear cell distribution and whether the response to Intuvax treatment is dependent on the histopathology. In addition, inclusion criterion 1 was updated to stress that an eligible patient should have at least one assessable metastasis in place after surgery. Change of exclusion criterion 3 to allow up to 10 mg/day per oral systemic corticosteroids. [more info available]

17 Oct 2017

Inclusion of additional immunohistology analysis for CD8+ cells at the GLP-compliant laboratory Histalim, to increase the quality of data. Collection of local laboratory results for creatinine at Nephrectomy visit. It was discovered that patients included in the study before 28 August 2017 had no central analysis of creatinine performed at Vaccination visit 1, Vaccination visit 2, and Nephrectomy visit, as specified in the protocol. A corrective action plan (CAPA) was written that described the situation and all actions to be made to resolve the issue, of which updating the protocol with collection of local creatinine results, if available, was one. Submissions of this serious breach were made to involved competent authorities and IECs in all countries as applicable. Merging of French-specific protocol criterion with the global (i.e. other country) protocol by addition of a country-specific exclusion criterion. The following non-substantial changes were made: removal of pre-defined stratification ratio, updated number of sites, updated study-administrative structure and extension of Intuvax shelf life.

25 Jun 2018

Added definition of the safety evaluation, that SAEs will be collected, and a description on how it is done in practice. Non-substantial changes were made to update the definition of EoS, updated procedure for collection and statistical analyses of post-study survival data as well as a study-administrative change.

12 Feb 2019

A new exploratory objective and endpoint relating to tumor response rate between screening and the first post-nephrectomy assessment has been added. The definition of baseline has been clarified for secondary endpoints based on RECIST for intermediate-risk patients included in the trial according to protocol versions before version Final 4.0 Non-substantial changes were made to clarify local and central imaging assessments, information about persons involved in conduct and reporting of the study, it was clarified that CR and PR do not need to be confirmed by repeat tumor measurements, the assessment of mismatch between patient and donor HLA types was clarified as well as the process of data collection in eCRF regarding AE follow-up.

29 May 2019

A non-substantial amendment was made to allow collection of post-study survival information more frequently; up to twice per year, instead of once per year.

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

http://www.ncbi.nlm.nih.gov/pubmed/27444986
http://www.ncbi.nlm.nih.gov/pubmed/31427204
http://www.ncbi.nlm.nih.gov/pubmed/30779531
http://www.ncbi.nlm.nih.gov/pubmed/30779529
http://www.ncbi.nlm.nih.gov/pubmed/29860937

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Clinical trials

Clinical Trial Results: An open-label, randomized, controlled, multicenter, phase II study evaluating safety and efficacy of intratumorally administered Intuvax pre-nephrectomy followed by Sunitinib post-nephrectomy, compared to Sunitinib post-nephrectomy in metastatic renal cell carcinoma patients

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Overall Survival - days (FAS)

Primary: Overall Survival - days (FAS)

Primary: Overall survival - days (PPS)

Primary: Overall survival - days (PPS)

Primary: 18-Months' Overall Survival - Rate (FAS)

Primary: 18-Months' Overall Survival - Rate (FAS)

Primary: 18-Months' Overall Survival Rate (PPS)

Primary: 18-Months' Overall Survival Rate (PPS)

Secondary: Progression-Free Survival

Secondary: Progression-Free Survival

Secondary: Objective Response Rate

Secondary: Objective Response Rate

Secondary: Best Overall Response

Secondary: Best Overall Response

Secondary: Disease Control Rate

Secondary: Disease Control Rate

Secondary: Duration of Response

Secondary: Duration of Response

Secondary: Duration of Clinical Benefit

Secondary: Duration of Clinical Benefit

Secondary: Duration of Stable Disease

Secondary: Duration of Stable Disease

Secondary: Time to Progression

Secondary: Time to Progression

Secondary: Number of Infiltrating CD8+ T-Cells

Secondary: Number of Infiltrating CD8+ T-Cells

Secondary: Physical Examination

Secondary: Physical Examination

Secondary: Vital Signs - Weight

Secondary: Vital Signs - Weight

Secondary: Vital Signs - Blood Pressure

Secondary: Vital Signs - Blood Pressure

Secondary: Vital Signs - Heart Rate

Secondary: Vital Signs - Heart Rate

Secondary: Vital Signs - Temperature

Secondary: Vital Signs - Temperature

Secondary: Laboratory Evaluation - Hematology

Secondary: Laboratory Evaluation - Hematology

Secondary: Laboratory Evaluation - Clinical Chemistry

Secondary: Laboratory Evaluation - Clinical Chemistry

Secondary: Laboratory Evaluation - Coagulation

Secondary: Laboratory Evaluation - Coagulation

Other pre-specified: ECOG Performance Status

Other pre-specified: ECOG Performance Status

Other pre-specified: Quality of Life - EORTC QLQ-C30

Other pre-specified: Quality of Life - EORTC QLQ-C30

Other pre-specified: Correlation between MHC mismatch and infiltrating CD8+ T cells

Other pre-specified: Correlation between MHC mismatch and infiltrating CD8+ T cells

Other pre-specified: Auto- and allo-immunization

Other pre-specified: Auto- and allo-immunization

Other pre-specified: Time to Treatment Failure

Other pre-specified: Time to Treatment Failure

Other pre-specified: Tumor Response from Screening to Sun-Start

Other pre-specified: Tumor Response from Screening to Sun-Start

Other pre-specified: Exploratory Cox Model Analyses

Other pre-specified: Exploratory Cox Model Analyses

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
An open-label, randomized, controlled, multicenter, phase II study evaluating safety and efficacy of intratumorally administered Intuvax pre-nephrectomy followed by Sunitinib post-nephrectomy, compared to Sunitinib post-nephrectomy in metastatic renal cell carcinoma patients