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Clinical Trial Results:
An open, dose-escalation Phase I/II study to assess the safety, immunogenicity and clinical activity of recPRAME + AS15 Antigen-Specific Cancer Immunotherapeutic as first-line treatment of patients with PRAME-positive metastatic melanoma

Summary
EudraCT number	2009-016636-13
Trial protocol	DE FR CZ
Global end of trial date	19 Dec 2016

Results information
Results version number	v2(current)
This version publication date	11 Nov 2020
First version publication date	04 Jan 2018
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

113173

ISRCTN number

US NCT number

NCT01149343

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, 44 2089904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, 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

19 Jun 2017

Is this the analysis of the primary completion data?

Yes

Primary completion date

11 Feb 2014

Global end of trial reached?

Yes

Global end of trial date

19 Dec 2016

Was the trial ended prematurely?

Main objective of the trial

This open-label, Phase I/II study contains two consecutive segments: a dose-escalation Phase I segment and a Phase II segment assessing the clinical activity of the recPRAME + AS15 ASCI at the dose selected. The co-primary objectives of the Phase I segment of the study were to document and characterize for each dose tested: - The dose limiting toxicity; - The anti-PRAME humoral immune response. The co-primary objectives of the Phase II segment of the study were to characterize: - The clinical activity of recPRAME + AS15 in terms of objective responses in the overall cohort; - Any occurrence of dose-limiting toxicity.

Protection of trial subjects

The patients were observed closely for at least 30 minutes following the administration of the study medication with appropriate medical treatment readily available in case of a rare anaphylactic reaction.

Background therapy

Evidence for comparator

Actual start date of recruitment

02 Jul 2010

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

1 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Czech Republic: 9

Country: Number of subjects enrolled

Germany: 33

Country: Number of subjects enrolled

France: 14

Country: Number of subjects enrolled

Italy: 30

Country: Number of subjects enrolled

Poland: 6

Country: Number of subjects enrolled

Russian Federation: 14

Worldwide total number of subjects

106

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 106 patients included in the total treated population were enrolled by 31 different study centers.

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 Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

The study is an open-label clinical trial.

Are arms mutually exclusive

Yes

GSK2302025A Cohort 1

Arm description

Male or female patients with histologically proven cutaneous melanoma received the investigational Low-Dose (LD) adjuvanted GSK2302025A immunotherapeutic vaccine, intramuscularly into the deltoid or lateral region of the thigh, with alternation on right or left side at each succeeding injection. Subjects received a total of 24 administrations in 4 cycles: 6 administrations given at 2 weeks intervals in cycle 1, 6 administrations given at 3 weeks intervals in cycle 2, 4 administrations given at 6 weeks intervals in cycle 3 and 4 administrations given at 3 months interval in cycle 4.

Arm type

Experimental

Investigational medicinal product name

Recombinant PRAME protein combined with the AS15 Adjuvant System GSK2302025A

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Patients received a total of 24 PRAME ASCI intramuscular administrations, into the deltoid or lateral region of the thigh, with alternation on right or left side at each succeeding injection, according to the following schedule: Cycle 1: 6 PRAME ASCI administrations given at 2-week intervals (weeks 0, 2, 4, 6, 8, 10); Cycle 2: 6 PRAME ASCI administrations given at 3-week intervals (weeks 14, 17, 20, 23, 26, 29); Cycle 3: 4 PRAME ASCI administrations given at 6-week intervals (weeks 33, 39, 45, 51); Cycle 4: 4 PRAME ASCI administrations given at 3-month intervals followed by 4 PRAME ASCI administrations given at 6-month intervals.

GSK2302025A Cohort 2

Arm description

Male or female patients with histologically proven cutaneous melanoma received the investigational Middle-Dose (MD) adjuvanted GSK2302025A immunotherapeutic vaccine, intramuscularly into the deltoid or lateral region of the thigh, with alternation on right or left side at each succeeding injection. Subjects received a total of 24 administrations in 4 cycles: 6 administrations given at 2 weeks intervals in cycle 1, 6 administrations given at 3 weeks intervals in cycle 2, 4 administrations given at 6 weeks intervals in cycle 3 and 4 administrations given at 3 months interval in cycle 4.

Arm type

Experimental

Investigational medicinal product name

Recombinant PRAME protein combined with the AS15 Adjuvant System GSK2302025A

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

GSK2302025A Cohort 3

Arm description

Male or female patients with histologically proven cutaneous melanoma received the investigational High-Dose (HD) adjuvanted GSK2302025A immunotherapeutic vaccine, intramuscularly into the deltoid or lateral region of the thigh, with alternation on right or left side at each succeeding injection. Subjects received a total of 24 administrations in 4 cycles: 6 administrations given at 2 weeks intervals in cycle 1, 6 administrations given at 3 weeks intervals in cycle 2, 4 administrations given at 6 weeks intervals in cycle 3 and 4 administrations given at 3 months interval in cycle 4.

Arm type

Experimental

Investigational medicinal product name

Recombinant PRAME protein combined with the AS15 Adjuvant System GSK2302025A

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

GSK2302025A Cohort 4

Arm description

In Phase 2 of the study subjects received the optimal investigational dose-level identified in Phase 1. Patients received a treatment consisting of 24 injections of the experimental GSK2302025A immunotherapeutic.

Arm type

Experimental

Investigational medicinal product name

Recombinant PRAME protein combined with the AS15 Adjuvant System GSK2302025A

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Number of subjects in period 1	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Started	20	24	22	40
Completed	0	0	0	0
Not completed	20	24	22	40
Adverse event, serious fatal	10	13	18	18
Consent withdrawn by subject	1	1	1	5
Recurrence / Progressive disease	-	-	1	-
Sponsor study termination	-	-	-	2
Unspecified	8	10	2	14
Lost to follow-up	1	-	-	1

Baseline characteristics

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Reporting group title

GSK2302025A Cohort 1

Reporting group description

Reporting group title

GSK2302025A Cohort 2

Reporting group description

Reporting group title

GSK2302025A Cohort 3

Reporting group description

Reporting group title

GSK2302025A Cohort 4

Reporting group description

Reporting group values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4	Total
Number of subjects	20	24	22	40
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	60.3 ± 14.9	60.8 ± 15.5	59.5 ± 15.2	60.7 ± 18.1	-
Gender categorical
Units: Subjects
Female	7	11	10	29	57
Male	13	13	12	11	49
Race/Ethnicity, Customized
Units: Subjects
White - Caucasian / European Heritage	20	23	21	40	104
Other	0	1	1	0	2

End points

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Reporting group title

GSK2302025A Cohort 1

Reporting group description

Reporting group title

GSK2302025A Cohort 2

Reporting group description

Reporting group title

GSK2302025A Cohort 3

Reporting group description

Reporting group title

GSK2302025A Cohort 4

Reporting group description

Primary: Number of patients with dose-limiting toxicity (Phase I)

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End point title

Number of patients with dose-limiting toxicity (Phase I) ^[1] ^[2]

End point description

The dose-limiting toxicities (DLT) were defined as follows: •An Antigen-Specific Cancer Immunotherapeutic (ASCI) related or possibly ASCI related grade 3 or higher toxicity. Grade 3 myalgia, arthralgia, headache, fever, rigors/chills and fatigue (including lethargy, malaise and asthenia) persisting for 48 hours despite therapy. •An ASCI related or possibly ASCI related grade 2 or higher allergic reaction occurring within 24 hours following the ASCI administration. •An ASCI related or possibly ASCI related decrease in renal function, with a creatinine clearance lower than (<) 40 milliliters per minute (mL/min). •An ASCI-related or possibly ASCI-related symptomatic and confirmed adrenal insufficiency. The grading used was defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0: Grade 3 DLT = severe DLT. Related = DLT considered by investigator as possibly related to product administration.

End point type

Primary

End point timeframe

During the study treatment (up to 4 years), for all patients

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 scope of this primary end point was descriptive, no statistical hypothesis test was performed.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3
Number of subjects analysed	20	24	22
Units: Days
Patients with DLT	0	1	1
Patients with related DLT	0	1	1
Patients with severe DLT	0	1	1
Brain oedema	0	1	0
Microalbuminuria	0	0	1
Proteinuria	0	0	1

No statistical analyses for this end point

Primary: Percentage of patients with anti-PReferentially expressed Antigen of MElanoma (Anti-PRAME) humoral immune response (Phase I)

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End point title

Percentage of patients with anti-PReferentially expressed Antigen of MElanoma (Anti-PRAME) humoral immune response (Phase I) ^[3] ^[4]

End point description

A seronegative/seropositive patient for anti-PRAME antibodies was a patient with antibody concentration lower (<)/ higher than or equal to (≥) cut-off level. Humoral immune response was defined as a) if baseline concentration < cut-off level: post treatment concentration ≥ cut-off level, or b) if baseline concentration ≥ cut-off level: post treatment concentration at least twice the baseline value. Cut-off values for seropositivity (by enzyme-linked immunosorbent assay [ELISA]) were 12 ELISA Units per milliliter (EL.U/mL).

End point type

Primary

End point timeframe

After the administration of dose 4 at Week 8

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 scope of this primary end point was descriptive, no statistical hypothesis test was performed.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3
Number of subjects analysed	13	13	17
Units: Percentage of patients
number (confidence interval 95%)
Percentage of patients	100 (75.3 to 100)	100 (75.3 to 100)	100 (80.5 to 100)

No statistical analyses for this end point

Primary: Number of patients with best overall response to study treatment (Phase II)

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End point title

Number of patients with best overall response to study treatment (Phase II) ^[5]

End point description

The best overall response is the best response recorded from the start of the treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started). In general the patient's best response assignment depended on the achievement of both measurement and confirmation criteria. The best overall response includes the complete response (CR) defined as disappearance of all targeted/non-targeted lesions and partial response (PR) defined as at least 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD and persistence of one or more non-targeted lesion(s).

End point type

Primary

End point timeframe

Up to study conclusion at year 4 + 1 month

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 scope of this primary end point was descriptive, no statistical hypothesis test was performed.

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
CR	0	0	0	0
PR	0	0	0	4

No statistical analyses for this end point

Secondary: Number of patients with any unsolicited adverse events (AEs), by maximum grading

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End point title

Number of patients with any unsolicited adverse events (AEs), by maximum grading

End point description

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. The grading to be used by the investigators for the assessment of the severity of adverse events (AEs) was defined as the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.

End point type

Secondary

End point timeframe

During the study treatment period until 30 days after the last administration

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
Grade 1	9	9	8	12
Grade 2	6	6	10	15
Grade 3	4	5	3	7
Grade 4	1	1	0	3
Grade 5	0	0	0	2

No statistical analyses for this end point

Secondary: Number of patients with Serious Adverse Events (SAEs), by maximum grading

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End point title

Number of patients with Serious Adverse Events (SAEs), by maximum grading

End point description

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. The grading to be used by the investigators for the assessment of the severity of adverse events (AEs) was defined as the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.

End point type

Secondary

End point timeframe

During the study period - up to 4 years + 1 month post last study treatment administration

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
Grade 1	0	0	0	0
Grade 2	0	0	1	0
Grade 3	2	2	1	0
Grade 4	1	1	0	3
Grade 5	0	0	0	2

No statistical analyses for this end point

Secondary: Number of patients with laboratory abnormalities versus baseline, by maximum grading

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End point title

Number of patients with laboratory abnormalities versus baseline, by maximum grading

End point description

Laboratory abnormalities belong to hematological and biochemical parameters such as: activated partial thromboplastin time prolonged [APTTP], alanine aminotransferase increased [ALT/I], alkaline phoshatase increased [APH/I], anemia [AN], asparatate aminostransferase increased [AST/I], blood bilirubin increased [BB/I], creatinine increased [CRE/I], gamma glumatymtransferase increased [GGT/I], hemoglobin increased [Hgb/I], hypoalbuminemia [HYP], lymphocyte count decreased [LYMC/D], lymphocyte count increased [LYMC/I], neutrophil count decreased [ NEUC/D], platelet count decreased [PLA/D], white blood cell decreased [WBC/D]. Parameter grades (G0,1,2,3,4,Uknown) were compared to baseline parameter grades (GUnknown,0,1,2,3), as defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009 [http://evs.nci.nih.gov/ftp1/CTCAE]. This endpoint presents values for [APTTP] grading versus baseline parameter grading.

End point type

Secondary

End point timeframe

During the study period - up to 4 years + 1 month post last study treatment administration

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
[APTTP], G0-GUnknown	0	0	0	0
[APTTP], G1-GUnknown	0	0	0	0
[APTTP], G2-GUnknown	0	0	0	0
[APTTP], G3-GUnknown	0	0	0	1
[APTTP], G4-GUnknown	0	0	0	0
[APTTP], GUknown-GUnknown	2	0	1	0
[APTTP], G0-G0	13	16	18	33
[APTTP], G1-G0	2	3	1	3
[APTTP], G2-G0	0	0	1	0
[APTTP], G3-G0	0	1	0	1
[APTTP], G4-G0	0	0	0	0
[APTTP], GUnknown-G0	2	0	1	0
[APTTP], G0-G1	0	1	0	1
[APTTP], G1-G1	0	2	0	0
[APTTP], G2-G1	0	0	0	1
[APTTP], G3-G1	0	0	0	0
[APTTP], G4-G1	0	0	0	0
[APTTP], GUnknown-G1	0	1	0	0
[APTTP], G0-G2	0	0	0	0
[APTTP], G1-G2	0	0	0	0
[APTTP], G2-G2	1	0	0	0
[APTTP], G3-G2	0	0	0	0
[APTTP], G4-G2	0	0	0	0
[APTTP], GUknown-G2	0	0	0	0

No statistical analyses for this end point

Secondary: Number of patients with laboratory abnormalities versus baseline, by maximum grading

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End point title

Number of patients with laboratory abnormalities versus baseline, by maximum grading

End point description

End point type

Secondary

End point timeframe

During the study period - up to 4 years + 1 month post last study treatment administration

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
[ALT/I], G0-G0	11	18	16	34
[ALT/I], G1-G0	4	4	5	1
[ALT/I], G2-G0	0	0	0	1
[ALT/I], G3-G0	0	0	0	0
[ALT/I], G4-G0	0	0	0	0
[ALT/I], GUknown-G0	2	0	1	0
[ALT/I], G0-G1	0	2	0	1
[ALT/I], G1-G1	3	0	0	3
[ALT/I], G2-G1	0	0	0	0
[ALT/I], G3-G1	0	0	0	0
[ALT/I], G4-G1	0	0	0	0
[ALT/I], GUknown-G1	0	0	0	0
[APH/I], G0-G0	16	20	15	33
[APH/I], G1-G0	1	3	5	5
[APH/I], G2-G0	0	0	1	1
[APH/I], G3-G0	0	0	0	0
[APH/I], G4-G0	0	0	0	0
[APH/I], GUknown-G0	2	0	1	0
[APH/I], G0-G1	0	0	0	0
[APH/I], G1-G1	0	0	0	1
[APH/I], G2-G1	0	1	0	0
[APH/I], G3-G1	0	0	0	0
[APH/I], G4-G1	0	0	0	0
[APH/I], GUknokwn-G1	0	0	0	0
[APH/I], G0-G2	0	0	0	0
[APH/I], G1-G2	0	0	0	0
[APH/I], G2-G2	0	0	0	0
[APH/I], G3-G2	1	0	0	0
[APH/I], G4-G2	0	0	0	0
[APH/I], GUknown-G2	0	0	0	0

No statistical analyses for this end point

Secondary: Number of patients with hematological and biochemical abnormalities versus baseline, by maximum grading

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End point title

Number of patients with hematological and biochemical abnormalities versus baseline, by maximum grading

End point description

End point type

Secondary

End point timeframe

During the study period - up to 4 years + 1 month post last study treatment administration

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
[AN], G0-G0	12	10	10	21
[AN], G1-G0	1	6	5	12
[AN], G2-G0	0	0	1	3
[AN], G3-G0	1	0	0	0
[AN], G4-G0	0	0	0	0
[AN], GUknown-G0	1	0	1	0
[AN], G0-G1	2	1	0	0
[AN], G1-G1	2	5	5	4
[AN], G2-G1	0	1	0	0
[AN], G3-G1	0	1	0	0
[AN], G4-G1	0	0	0	0
[AN], GUnknown-G1	1	0	0	0
[AST/I], G0-G0	13	18	17	36
[AST/I], G1-G0	3	6	4	2
[AST/I], G2-G0	0	0	0	0
[AST/I], G3-G0	0	0	0	0
[AST/I], G4-G0	0	0	0	0
[AST/I], GUnknown-G0	1	0	1	0
[AST/I], G0-G1	1	0	0	0
[AST/I], G1-G1	1	0	0	2
[AST/I], G2-G1	0	0	0	0
[AST/I], G3-G1	0	0	0	0
[AST/I], G4-G1	0	0	0	0
[AST/I], GUnknown-G1	1	0	0	0
[BB/I], G0-G0	16	21	19	38
[BB/I], G1-G0	1	2	1	0
[BB/I], G2-G0	1	0	0	0
[BB/I], G3-G0	0	0	0	0
[BB/I], G4-G0	0	0	0	0
[BB/I], GUnknown-G0	2	0	1	0
[BB/I], G0-G1	0	0	0	0
[BB/I], G1-G1	0	1	1	1
[BB/I], G2-G1	0	0	0	1
[BB/I], G3-G1	0	0	0	0
[BB/I], G4-G1	0	0	0	0
[BB/I], GUnknown-G1	0	0	0	0

No statistical analyses for this end point

Secondary: Number of patients with laboratory hematological and biochemical abnormalities versus baseline, by maximum grading

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End point title

Number of patients with laboratory hematological and biochemical abnormalities versus baseline, by maximum grading

End point description

End point type

Secondary

End point timeframe

During the study period - up to 4 years + 1 month post last study treatment administration

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
[CRE/I], G0-G0	20	22	20	33
[CRE/I], G1-G0	0	0	1	6
[CRE/I], G2-G0	0	0	0	0
[CRE/I], G3-G0	0	0	0	0
[CRE/I], G4-G0	0	0	0	0
[CRE/I], GUnknown-G0	0	0	0	0
[CRE/I], G0-G1	0	0	0	0
[CRE/I], G1-G1	0	1	1	0
[CRE/I], G2-G1	0	0	0	0
[CRE/I], G3-G1	0	0	0	0
[CRE/I], G4-G1	0	0	0	0
[CRE/I], GUnknown-G1	0	0	0	0
[CRE/I], G0-G2	0	0	0	0
[CRE/I], G1-G2	0	0	0	0
[CRE/I], G2-G2	0	1	0	1
[CRE/I], G3-G2	0	0	0	0
[CRE/I], G4-G2	0	0	0	0
[CRE/I], GUknown-G2	0	0	0	0
[GGT/I], G0-G0	10	17	14	30
[GGT/I], G1-G0	1	1	1	4
[GGT/I], G2-G0	2	2	1	0
[GGT/I], G3-G0	0	0	0	0
[GGT/I], G4-G0	0	0	0	1
[GGT/I], GUnknown-G0	1	0	1	0
[GGT/I], G0-G1	2	1	1	1
[GGT/I], G1-G1	0	1	1	3
[GGT/I], G2-G1	1	1	0	0
[GGT/I], G3-G1	0	0	1	0
[GGT/I], G4-G1	0	0	0	0
[GGT/I], GUnknown-G1	1	0	0	0
[GGT/I], G0-G2	0	0	0	0
[GGT/I], G1-G2	0	1	0	0
[GGT/I], G2-G2	0	0	0	0
[GGT/I], G3-G2	1	0	2	0
[GGT/I], G4-G2	0	0	0	0
[GGT/I], GUnknown-G2	1	0	0	0
[GGT/I], G0-G3	0	0	0	0
[GGT/I], G1-G3	0	0	0	0
[GGT/I], G2-G3	0	0	0	0
[GGT/I], G3-G3	0	0	0	1
[GGT/I], G4-G3	0	0	0	0
[GGT/I], GUnknown-G3	0	0	0	0

No statistical analyses for this end point

Secondary: Number of patients with laboratory hematological and biochemical abnormalities versus baseline, by maximum grading

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End point title

Number of patients with laboratory hematological and biochemical abnormalities versus baseline, by maximum grading

End point description

End point type

Secondary

End point timeframe

During the study period - up to 4 years + 1 month post last study treatment administration

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
[Hgb/I], G0-G0	16	24	21	37
[Hgb/I], G1-G0	0	0	0	2
[Hgb/I], G2-G0	0	0	0	0
[Hgb/I], G3-G0	0	0	0	0
[Hgb/I], G4-G0	0	0	0	0
[Hgb/I], GUnknown-G0	2	0	1	0
[Hgb/I], G0-G1	0	0	0	0
[Hgb/I], G1-G1	1	0	0	0
[Hgb/I], G2-G1	0	0	0	1
[Hgb/I], G3-G1	0	0	0	0
[Hgb/I], G4-G1	0	0	0	0
[Hgb/I], GUnknown-G1	0	0	0	0
[Hgb/I], G0-G2	0	0	0	0
[Hgb/I], G1-G2	1	0	0	0
[Hgb/I], G2-G2	0	0	0	0
[Hgb/I], G3-G2	0	0	0	0
[Hgb/I], G4-G2	0	0	0	0
[Hgb/I], GUnknown-G2	0	0	0	0
[HYP], G0-G0	13	17	18	30
[HYP], G1-G0	2	5	2	5
[HYP], G2-G0	0	1	0	1
[HYP], G3-G0	0	0	0	0
[HYP], G4-G0	0	0	0	0
[HYP], GUnknown-G0	3	0	2	0
[HYP], G0-G1	0	0	0	0
[HYP], G1-G1	1	1	0	3
[HYP], G2-G1	1	0	0	0
[HYP], G3-G1	0	0	0	0
[HYP], G4-G1	0	0	0	0
[HYP], GUnknown-G1	0	0	0	0
[HYP], G0-G3	0	0	0	1
[HYP], G1-G3	0	0	0	0
[HYP], G2-G3	0	0	0	0
[HYP], G3-G3	0	0	0	0
[HYP], G4-G3	0	0	0	0
[HYP], GUnknown-G3	0	0	0	0

No statistical analyses for this end point

Secondary: Number of patients with abnormal hematological and biochemical results versus baseline, by maximum grading

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End point title

Number of patients with abnormal hematological and biochemical results versus baseline, by maximum grading

End point description

End point type

Secondary

End point timeframe

During the study period - up to 4 years + 1 month post last study treatment administration

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
[LYMC/D], G0-G0	10	14	14	28
[LYMC/D], G1-G0	3	4	3	4
[LYMC/D], G2-G0	1	1	0	0
[LYMC/D], G3-G0	0	0	0	0
[LYMC/D], G4-G0	0	0	0	0
[LYMC/D], GUnknown-G0	0	0	1	0
[LYMC/D], G0-G1	0	1	1	2
[LYMC/D], G1-G1	3	3	2	5
[LYMC/D], G2-G1	1	0	0	0
[LYMC/D], G3-G1	0	0	0	0
[LYMC/D], G4-G1	0	0	0	0
[LYMC/D], GUnknown-G1	1	1	0	0
[LYMC/D], G0-G2	0	0	0	0
[LYMC/D], G1-G2	0	0	1	0
[LYMC/D], G2-G2	0	0	0	1
[LYMC/D], G3-G2	0	0	0	0
[LYMC/D], G4-G2	0	0	0	0
[LYMC/D], GUnknown-G2	0	0	0	0
[LYMC/D], G0-G3	0	0	0	0
[LYMC/D], G1-G3	0	0	0	0
[LYMC/D], G2-G3	0	0	0	0
[LYMC/D], G3-G3	0	0	0	0
[LYMC/D], G4-G3	0	0	0	0
[LYMC/D], GUnknown-G3	1	0	0	0
[LYMC/I], G0-G0	16	23	21	40
[LYMC/I], G1-G0	0	0	0	0
[LYMC/I], G2-G0	2	0	0	0
[LYMC/I], G3-G0	0	0	0	0
[LYMC/I], G4-G0	0	0	0	0
[LYMC/I], GUnknown-G0	2	1	1	0

No statistical analyses for this end point

Secondary: Number of patients with abnormal hematological and biochemical results versus baseline, by maximum grading

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End point title

Number of patients with abnormal hematological and biochemical results versus baseline, by maximum grading

End point description

Laboratory abnormalities belong to hematological and biochemical parameters such as: activated partial thromboplastin time prolonged [APTTP], alanine aminotransferase increased [ALT/I], alkaline phoshatase increased [APH/I], anemia [AN], asparatate aminostransferase increased [AST/I], blood bilirubin increased [BB/I], creatinine increased [CRE/I], gamma glumatymtransferase increased [GGT/I], hemoglobin increased [Hgb/I], hypoalbuminemia [HYP], lymphocyte count decreased [LYMC/D], lymphocyte count increased [LYMC/I], neutrophil count decreased [NEUC/D], platelet count decreased [PLA/D], white blood cell decreased [WBC/D]. Parameter grades (G0,1,2,3,4,Uknown) were compared to baseline parameter grades (GUnknown,0,1,2,3), as defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009 [http://evs.nci.nih.gov/ftp1/CTCAE]. This endpoint presents values for [NEUC/D], [PLA/D] and [WBC/D] grading versus baseline parameter grading.

End point type

Secondary

End point timeframe

During the study period - up to 4 years + 1 month post last study treatment administration

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
[NEUC/D], G0-G0	17	21	21	39
[NEUC/D], G1-G0	1	2	0	0
[NEUC/D], G2-G0	0	0	0	0
[NEUC/D], G3-G0	0	0	0	0
[NEUC/D], G4-G0	0	0	0	0
[NEUC/D], GUnknown-G0	2	1	1	0
[NEUC/D], G0-G1	0	0	0	0
[NEUC/D], G1-G1	0	0	0	1
[NEUC/D], G2-G1	0	0	0	0
[NEUC/D], G3-G1	0	0	0	0
[NEUC/D], G4-G1	0	0	0	0
[NEUC/D], GUnknown-G1	0	0	0	0
[PLA/D], G0-G0	17	24	20	38
[PLA/D], G1-G0	1	0	0	2
[PLA/D], G2-G0	0	0	0	0
[PLA/D], G3-G0	0	0	0	0
[PLA/D], G4-G0	0	0	0	0
[PLA/D], GUnknown-G0	2	0	1	0
[PLA/D], G0-G1	0	0	0	0
[PLA/D], G1-G1	0	0	1	0
[PLA/D], G2-G1	0	0	0	0
[PLA/D], G3-G1	0	0	0	0
[PLA/D], G4-G1	0	0	0	0
[PLA/D], GUnknown-G1	0	0	0	0
[WBC/D], G0-G0	14	21	19	34
[WBC/D], G1-G0	2	1	1	3
[WBC/D], G2-G0	0	0	0	0
[WBC/D], G3-G0	0	0	0	0
[WBC/D], G4-G0	0	0	0	0
[WBC/D], GUnknown-G0	2	0	1	0
[WBC/D], G0-G1	1	0	0	2
[WBC/D], G1-G1	1	2	1	1
[WBC/D], G2-G1	0	0	0	0
[WBC/D], G3-G1	0	0	0	0
[WBC/D], G4-G1	0	0	0	0
[WBC/D], GUnknown-G1	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of patients with anti-PRAME cellular (T-cell) response (Phase I)

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End point title

Percentage of patients with anti-PRAME cellular (T-cell) response (Phase I) ^[6]

End point description

Cellular response was defined as: Geometric Mean Response (GMR) above the 2.68 cut-off value and at least a four-fold increase of PRAME- specific Cluster of Differentiation (CD) 4/8 T cells. Considering that 2 studies failed to demonstrate clinical efficacy of recombinant protein based cancer vaccines, GSK decided in 2014 to stop the development and to stop recruitment in all the ongoing clinical studies. The decision was made to end the study (i.e., stopping patient enrollment, follow-ups, sample collection and analysis of samples for research purposes). Patients still on treatment at the time of the protocol amendment were offered to continue the administration of the study treatment until the last dose or until recurrence, whichever came first, or until the patient or the investigator decided to stop the study treatment. No further active protocol visit/contact was performed except for the concluding visit 30 days after the last treatment administration.

End point type

Secondary

End point timeframe

Up to Data Lock Point at Week 8

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3
Number of subjects analysed	8	11	14
Units: Percentage of patients
number (confidence interval 95%)
Patients with pre+post-administration results CD4	100 (63.1 to 100)	100 (71.5 to 100)	100 (76.8 to 100)
Responders CD4	75.0 (34.9 to 96.8)	45.5 (16.7 to 76.6)	57.1 (28.9 to 82.3)
Patients with pre+post-administration results CD8	100 (63.1 to 100)	100 (66.4 to 100)	100 (63.1 to 100)
Responders CD8	0.0 (0.0 to 36.9)	0.0 (0.0 to 33.6)	0.0 (0.0 to 36.9)

No statistical analyses for this end point

Secondary: Number of subjects with anti-PRAME humoral immune response (Phase I & II)

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End point title

Number of subjects with anti-PRAME humoral immune response (Phase I & II)

End point description

A seropositive subject is a subject whose antibody concentrations are greater than or equal to the assay cut-off value of 12 EL/mL.

End point type

Secondary

End point timeframe

At Week 0, 4, 8, 10, 12, 29, 51, 75, 99 123, 147 and conclusion visit at 30 days post last treatment administration for each patient

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
anti-PRAME,week 0	0	0	0	2
anti-PRAME,week 4	11	14	18	33
anti-PRAME,week 8	14	13	21	33
anti-PRAME,week 10	10	12	19	33
anti-PRAME,week 12	9	9	16	28
anti-PRAME,week 29	2	4	5	13
anti-PRAME,week 51	1	3	3	7
anti-PRAME, week 75	2	2	2	1
anti-PRAME, week 99	2	2	2	0
anti-PRAME, week 123	1	1	1	0
anti-PRAME, week 147	1	0	0	0
anti-PRAME, conclusion visit	6	12	8	23

No statistical analyses for this end point

Secondary: Number of subjects with best overall response, including Mixed Response (MxR) and Slow Progressive Disease (SPD) criteria (Phase I & II)

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End point title

Number of subjects with best overall response, including Mixed Response (MxR) and Slow Progressive Disease (SPD) criteria (Phase I & II)

End point description

Tumor response was assessed by the RECIST criteria, where SD for target lesions refers to neither enough shrinkage to qualify for CR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started. For non-targeted lesions it refers to persistence of one or more nom-target lesions. Progressive disease is related to a clear increase of diameters of lesions taking as references the smallest diameters recorded since the treatment started OR the appearance of one or more new lesions OR both of these. Mixed response is defined as at least 30% decrease in the longest diameter (LD) occurring in at least one target lesion recorded and measured at baseline. Such response occurring in otherwise SD or PD status of the LD of target lesions were classified as “SD with target lesion regression” or “PD with target lesion regression”, respectively. New lesion(s) in otherwise PR status of the LD of target lesions were “PR with new lesion”.

End point type

Secondary

End point timeframe

At 30 days after the last treatment administration for each patient

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
PR	0	0	0	0
CR	0	0	0	4
MxR: SD with target lesion regression	0	0	0	0
MxR: PD with target lesion regression	2	2	2	3
MxR: PR with new lesion	0	0	1	0
SD/PR	0	1	1	3
SD without mixed response	2	0	1	1
PD with SPD criteria	3	5	4	19
PD without SPD/MxR	4	12	8	9
Non Evaluable	2	1	0	1
Missing Best overall response	7	3	5	0

No statistical analyses for this end point

Secondary: The anti-Protein D humoral response (Phase I)

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End point title

The anti-Protein D humoral response (Phase I)

End point description

Analysis of immunogenicity for anti-PD antibodies was not performed, following negative results to the NCT00480025 study which assessed another study product from same technology platform. For this study, the main analysis of the dose-escalation Phase I segment was performed according to protocol when all patients enrolled in the Phase I segment had received the first 4 treatment doses and had completed Week 8. The main analysis of the Phase II segment was performed according to protocol when all patients had either completed the treatment until the end of Cycle 3 or had been withdrawn from the study treatment, with the exception of anti-PD antibody responses and PRAME-specific cellular responses which were not yet performed. All samples that had been collected but not yet tested were not tested by default, except if a scientific rationale remained relevant.

End point type

Secondary

End point timeframe

At Week 0, 4, 8, 12, 29, 51, 75, 99, 123, 147, 30 days after the last treatment administration for each patient, with follow-up, 3, 6, 9 and 12 months after concluding visit

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	0 ^[7]	0 ^[8]	0 ^[9]	0 ^[10]
Units: Titer
geometric mean (confidence interval 95%)
Titer	( to )	( to )	( to )	( to )

Notes
[7] - Analysis of immunogenicity for anti-PD antibodies was not performed.
[8] - Analysis of immunogenicity for anti-PD antibodies was not performed.
[9] - Analysis of immunogenicity for anti-PD antibodies was not performed.
[10] - Analysis of immunogenicity for anti-PD antibodies was not performed.

No statistical analyses for this end point

Secondary: The anti-Cytosine Phosphate Guanosine oligodeoxynucleotide (CpG) humoral response (Phase I & II)

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End point title

The anti-Cytosine Phosphate Guanosine oligodeoxynucleotide (CpG) humoral response (Phase I & II)

End point description

Analysis of immunogenicity for anti-CpG antibodies was not performed, following negative results to the NCT00480025 study which assessed another study product from same technology platform. For this study, the main analysis of the dose-escalation Phase I segment was performed according to protocol when all patients enrolled in the Phase I segment had received the first 4 treatment doses and had completed Week 8. The main analysis of the Phase II segment was performed according to protocol when all patients had either completed the treatment until the end of Cycle 3 or had been withdrawn from the study treatment, with the exception of anti-CpG antibody responses and PRAME-specific cellular responses which were not yet performed. All samples that had been collected but not yet tested were not tested by default, except if a scientific rationale remained relevant.

End point type

Secondary

End point timeframe

At Week 0, 4, 8, 12, 29, 51, years 1.5, 2, 2.5, 3, 3.5, 4 years + 1 month, with follow-up, 3, 6, 9 and 12 months after concluding visit

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	0 ^[11]	0 ^[12]	0 ^[13]	0 ^[14]
Units: Specifc T-cells/million T-cells
arithmetic mean (standard deviation)
Specifc T-cells/million T-cells	±	±	±	±

Notes
[11] - Analysis of immunogenicity for anti-CpG antibodies was not performed.
[12] - Analysis of immunogenicity for anti-CpG antibodies was not performed.
[13] - Analysis of immunogenicity for anti-CpG antibodies was not performed.
[14] - Analysis of immunogenicity for anti-CpG antibodies was not performed.

No statistical analyses for this end point

Secondary: Time to treatment failure, progression free survival, overall survival and duration of response (Phase I & II)

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End point title

Time to treatment failure, progression free survival, overall survival and duration of response (Phase I & II)

End point description

Time to treatment failure (TTF) was defined as the time from first administration of study product until the date of the last administration of the product, irrespective of the reason for study treatment discontinuation. Progression-free survival (PFS) was defined as the time from first adminsitration of study product until the date of either disease progression or death (for whateveer reason), whichever comes first. Overall survival (OS) was defined as the time from first administration of study product until death. Duration of response (DR) was defined as the time from the first objective response (OR) or SD assessment until the first assessment of PD. The value "9999" is a placeholder as the 95% confidence interval lower limit was below the limit of detection.

End point type

Secondary

End point timeframe

Up to Month 54

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Months
median (confidence interval 95%)
TTF	2.3 (1.0 to 4.9)	2.3 (1.3 to 4.2)	3.0 (2.3 to 4.9)	4.6 (2.7 to 5.3)
PFS	2.7 (1.4 to 2.9)	2.7 (1.0 to 2.8)	2.8 (2.1 to 2.9)	2.8 (2.7 to 3.3)
OS	17.0 (8.1 to 9999)	11.5 (7.3 to 9999)	10.8 (8.4 to 25.5)	23.0 (15.5 to 9999)
DR	43.8 (19.0 to 48.6)	42.4 (23.7 to 45.9)	42.1 (40.1 to 46.0)	26.5 (22.8 to 28.0)

No statistical analyses for this end point

Secondary: Duration of response for patients with CR, PR and SD or SD/PR status (Phase II)

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End point title

Duration of response for patients with CR, PR and SD or SD/PR status (Phase II)

End point description

Following negative results to the NCT00480025 study which assessed another study product from same technology platform. For this study, the main analysis of the dose-escalation Phase I segment was performed according to protocol when all patients enrolled in the Phase I segment had received the first 4 treatment doses and had completed Week 8. The main analysis of the Phase II segment was performed according to protocol when all patients had either completed the treatment until the end of Cycle 3 or had been withdrawn from the study treatment, with the exception of anti-CpG/anti-PD antibody responses and PRAME-specific cellular responses which were not yet performed. All samples that had been collected but not yet tested were not tested by default, except if a scientific rationale remained relevant.

End point type

Secondary

End point timeframe

Up to data lock point LPLV for Main analysis in Phase II

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	0 ^[15]	0 ^[16]	0 ^[17]	0 ^[18]
Units: Months
median (confidence interval 95%)
Months	( to )	( to )	( to )	( to )

Notes
[15] - This analysis was not performed.
[16] - This analysis was not performed.
[17] - This analysis was not performed.
[18] - This analysis was not performed.

No statistical analyses for this end point

Secondary: Number of subjects with stable disease (SD), progressive disease (PD), mixed response (MR) (Phase I & II)

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End point title

Number of subjects with stable disease (SD), progressive disease (PD), mixed response (MR) (Phase I & II)

End point description

End point type

Secondary

End point timeframe

At 30 days after the last treatment administration for each patient

End point values	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Number of subjects analysed	20	24	22	40
Units: Participants
Complete response	0	0	0	0
Partial response	0	0	0	4
Stable disease	2	1	1	1
Stable Disease/Progressive disease	0	1	1	3
Progressive disease	9	18	15	31
Non Evaluable	2	1	0	1
Missing Best overall response	7	3	5	0
Disease control: Yes	2	2	2	8
Disease control: No	18	22	20	32

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From study start to Month 49.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

GSK2302025A Cohort 1

Reporting group description

Subjects will receive investigational dose-level A (different from dose-levels B and C). Patients will receive a treatment consisting of 24 injections of the experimental GSK2302025A immunotherapeutic

Reporting group title

GSK2302025A Cohort 2

Reporting group description

Subjects will receive investigational dose-level B (different from dose-levels A and C). Patients will receive a treatment consisting of 24 injections of the experimental GSK2302025A immunotherapeutic

Reporting group title

GSK2302025A Cohort 3

Reporting group description

Subjects will receive investigational dose-level C (different from dose-levels A and B). Patients will receive a treatment consisting of 24 injections of the experimental GSK2302025A immunotherapeutic

Reporting group title

GSK2302025A Cohort 4

Reporting group description

In Phase 2 of the study subjects will receive the optimal investigational dose-level identified in Phase 1. Patients will receive a treatment consisting of 24 injections of the experimental GSK2302025A immunotherapeutic

Serious adverse events	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 20 (15.00%)	3 / 24 (12.50%)	2 / 22 (9.09%)	5 / 40 (12.50%)
number of deaths (all causes)	0	0	0	2
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal neoplasm
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Circulatory collapse
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Brain oedema
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sciatica
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Intestinal obstruction
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholestasis
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Pneumothorax
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Skin ulcer
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Bursitis
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Erysipelas
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infected skin ulcer
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Subcutaneous abscess
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	GSK2302025A Cohort 1	GSK2302025A Cohort 2	GSK2302025A Cohort 3	GSK2302025A Cohort 4
Total subjects affected by non serious adverse events
subjects affected / exposed	19 / 20 (95.00%)	21 / 24 (87.50%)	21 / 22 (95.45%)	37 / 40 (92.50%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Vascular disorders
Arteriosclerosis moenckeberg-type
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Haemorrhage
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Hot flush
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	2 / 40 (5.00%)
occurrences all number	0	0	0	2
Hyperaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	1	0
Hypertension
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	2 / 22 (9.09%)	2 / 40 (5.00%)
occurrences all number	1	0	3	2
Hypotension
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	1 / 40 (2.50%)
occurrences all number	1	0	1	1
Lymphoedema
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Lymphostasis
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Peripheral arterial occlusive disease
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	1	0
Peripheral coldness
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Thrombophlebitis
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Surgical and medical procedures
Catheter placement
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Tooth extraction
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	2
General disorders and administration site conditions
Administration site induration
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	3	0
Administration site pain
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	1 / 22 (4.55%)	2 / 40 (5.00%)
occurrences all number	0	2	2	4
Asthenia
subjects affected / exposed	2 / 20 (10.00%)	0 / 24 (0.00%)	6 / 22 (27.27%)	13 / 40 (32.50%)
occurrences all number	2	0	21	32
Axillary pain
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Chest discomfort
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	6	0	0	0
Chills
subjects affected / exposed	4 / 20 (20.00%)	1 / 24 (4.17%)	4 / 22 (18.18%)	8 / 40 (20.00%)
occurrences all number	10	2	14	14
Fatigue
subjects affected / exposed	4 / 20 (20.00%)	7 / 24 (29.17%)	6 / 22 (27.27%)	7 / 40 (17.50%)
occurrences all number	10	36	10	12
Feeling cold
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	2	0	0	0
Feeling hot
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Gait disturbance
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Hyperplasia
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Hyperthermia
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	1	0	1	0
Inflammation
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	1	0	0	1
Influenza like illness
subjects affected / exposed	4 / 20 (20.00%)	6 / 24 (25.00%)	7 / 22 (31.82%)	13 / 40 (32.50%)
occurrences all number	18	11	16	29
Injection site discomfort
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Injection site erythema
subjects affected / exposed	3 / 20 (15.00%)	7 / 24 (29.17%)	7 / 22 (31.82%)	8 / 40 (20.00%)
occurrences all number	13	17	14	18
Injection site induration
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	4	0
Injection site inflammation
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	2	0	0
Injection site pain
subjects affected / exposed	9 / 20 (45.00%)	10 / 24 (41.67%)	12 / 22 (54.55%)	24 / 40 (60.00%)
occurrences all number	39	32	51	90
Injection site oedema
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	2 / 22 (9.09%)	1 / 40 (2.50%)
occurrences all number	0	3	4	1
Injection site pruritus
subjects affected / exposed	2 / 20 (10.00%)	2 / 24 (8.33%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	2	2	8	0
Injection site reaction
subjects affected / exposed	5 / 20 (25.00%)	4 / 24 (16.67%)	2 / 22 (9.09%)	2 / 40 (5.00%)
occurrences all number	6	8	5	3
Injection site swelling
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	2 / 22 (9.09%)	0 / 40 (0.00%)
occurrences all number	0	4	4	0
Malaise
subjects affected / exposed	1 / 20 (5.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	2	1	0	3
Oedema
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	2 / 22 (9.09%)	0 / 40 (0.00%)
occurrences all number	0	0	3	0
Oedema peripheral
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	1	1	0
Pain
subjects affected / exposed	2 / 20 (10.00%)	0 / 24 (0.00%)	3 / 22 (13.64%)	8 / 40 (20.00%)
occurrences all number	2	0	4	9
Pyrexia
subjects affected / exposed	6 / 20 (30.00%)	8 / 24 (33.33%)	5 / 22 (22.73%)	22 / 40 (55.00%)
occurrences all number	20	22	8	86
Swelling
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	2 / 40 (5.00%)
occurrences all number	0	0	0	4
Xerosis
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	1	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Reproductive system and breast disorders
Metrorrhagia
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Uterine haemorrhage
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 20 (0.00%)	2 / 24 (8.33%)	0 / 22 (0.00%)	4 / 40 (10.00%)
occurrences all number	0	6	0	4
Dyspnoea
subjects affected / exposed	1 / 20 (5.00%)	2 / 24 (8.33%)	0 / 22 (0.00%)	2 / 40 (5.00%)
occurrences all number	2	2	0	2
Haemoptysis
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Oropharyngeal pain
subjects affected / exposed	1 / 20 (5.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	2	0	0
Respiratory disorder
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	2	0	0
Anxiety
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Confusional state
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	1	0
Depression
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	1 / 40 (2.50%)
occurrences all number	0	0	1	1
Dissociation
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Insomnia
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	1 / 22 (4.55%)	1 / 40 (2.50%)
occurrences all number	0	1	1	1
Mood altered
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	1	0
Investigations
Antinuclear antibody increased
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Blood glucose increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Blood lactic acid increased
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	1 / 40 (2.50%)
occurrences all number	0	0	1	2
Blood urea increased
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Body temperature increased
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Cortisol decreased
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	2 / 40 (5.00%)
occurrences all number	0	0	0	2
Cortisol increased
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Creatinine renal clearance decreased
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	4 / 40 (10.00%)
occurrences all number	0	1	0	4
Eosinophil count increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	1	0
Haemoglobin decreased
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Liver function test
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Injury, poisoning and procedural complications
Traumatic haematoma
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Cardiac disorders
Nodal arrhythmia
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Palpitations
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Sinus tachycardia
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Tachycardia
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Nervous system disorders
Amnesia
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	2	0
Burning sensation
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Dizziness
subjects affected / exposed	2 / 20 (10.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	2 / 40 (5.00%)
occurrences all number	2	0	1	2
Headache
subjects affected / exposed	6 / 20 (30.00%)	5 / 24 (20.83%)	4 / 22 (18.18%)	7 / 40 (17.50%)
occurrences all number	12	43	9	12
Neuralgia
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	1	0	1	0
Paraesthesia
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	1	0	0	1
Parosmia
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Sciatica
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Sensory loss
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Seizure
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Somnolence
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Tremor
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 20 (0.00%)	3 / 24 (12.50%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	3	0	1
Leukopenia
subjects affected / exposed	1 / 20 (5.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	1	0	0
Lymph node pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Neutropenia
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Ear and labyrinth disorders
Ear haemorrhage
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	1	0
Ear pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Hypoacusis
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Tinnitus
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Vertigo
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Eye disorders
Conjunctivitis allergic
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Eyelid oedema
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	1 / 20 (5.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	1	0	0
Abdominal distension
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	1 / 40 (2.50%)
occurrences all number	0	0	1	1
Abdominal pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	2 / 22 (9.09%)	3 / 40 (7.50%)
occurrences all number	1	0	4	3
Abdominal pain upper
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	2 / 22 (9.09%)	1 / 40 (2.50%)
occurrences all number	0	0	2	1
Constipation
subjects affected / exposed	1 / 20 (5.00%)	2 / 24 (8.33%)	2 / 22 (9.09%)	3 / 40 (7.50%)
occurrences all number	1	2	2	3
Dental caries
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Diarrhoea
subjects affected / exposed	1 / 20 (5.00%)	1 / 24 (4.17%)	1 / 22 (4.55%)	5 / 40 (12.50%)
occurrences all number	2	1	1	7
Dry mouth
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Dysphagia
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	2	0	0
Flatulence
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal motility disorder
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Nausea
subjects affected / exposed	5 / 20 (25.00%)	4 / 24 (16.67%)	2 / 22 (9.09%)	11 / 40 (27.50%)
occurrences all number	5	8	2	14
Odynophagia
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Oesophagitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Vomiting
subjects affected / exposed	2 / 20 (10.00%)	4 / 24 (16.67%)	0 / 22 (0.00%)	5 / 40 (12.50%)
occurrences all number	2	8	0	5
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Alopecia
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Dermatitis atopic
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	2
Dry skin
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Erythema
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	3 / 22 (13.64%)	0 / 40 (0.00%)
occurrences all number	0	0	4	0
Hyperhidrosis
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	1	0
Intertrigo
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	1	0
Papule
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Pruritus
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	2 / 40 (5.00%)
occurrences all number	1	0	2	2
Purpura senile
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Rash
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	1 / 22 (4.55%)	1 / 40 (2.50%)
occurrences all number	0	1	1	1
Rash pruritic
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Skin lesion
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Skin irritation
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Vitiligo
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	2 / 40 (5.00%)
occurrences all number	1	0	0	2
Renal and urinary disorders
Albuminuria
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Hyperoxaluria
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Microalbuminuria
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	2 / 22 (9.09%)	2 / 40 (5.00%)
occurrences all number	0	0	4	3
Nocturia
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Pollakiuria
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	1	0
Proteinuria
subjects affected / exposed	1 / 20 (5.00%)	1 / 24 (4.17%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	1	2	2	0
Polyuria
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Renal colic
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Renal impairment
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	1	0
Glucocorticoid deficiency
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	2 / 40 (5.00%)
occurrences all number	0	0	0	2
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 20 (5.00%)	2 / 24 (8.33%)	1 / 22 (4.55%)	6 / 40 (15.00%)
occurrences all number	1	24	1	7
Back pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	2 / 40 (5.00%)
occurrences all number	2	0	1	2
Bone pain
subjects affected / exposed	2 / 20 (10.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	5	2	0	0
Groin pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	1 / 40 (2.50%)
occurrences all number	1	0	1	1
Hypercreatinaemia
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Joint ankylosis
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Joint swelling
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Limb discomfort
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Musculoskeletal chest pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Muscle spasms
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	4 / 40 (10.00%)
occurrences all number	0	0	1	6
Musculoskeletal pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Myalgia
subjects affected / exposed	4 / 20 (20.00%)	2 / 24 (8.33%)	1 / 22 (4.55%)	5 / 40 (12.50%)
occurrences all number	5	5	1	5
Pain in extremity
subjects affected / exposed	1 / 20 (5.00%)	2 / 24 (8.33%)	2 / 22 (9.09%)	8 / 40 (20.00%)
occurrences all number	1	13	3	9
Infections and infestations
Bacteriuria
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Bronchitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	3 / 40 (7.50%)
occurrences all number	0	0	0	3
Bronchitis viral
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Conjunctivitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Cystitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	2 / 40 (5.00%)
occurrences all number	0	0	0	2
Infection
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Influenza
subjects affected / exposed	2 / 20 (10.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	3	0	0	1
Localised infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Oral herpes
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Periodontitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	0 / 40 (0.00%)
occurrences all number	0	0	1	0
Pharyngitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	1 / 40 (2.50%)
occurrences all number	0	0	1	1
Rash pustular
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1
Rhinitis
subjects affected / exposed	1 / 20 (5.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	4 / 40 (10.00%)
occurrences all number	1	1	0	4
Skin infection
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Tinea infection
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Upper respiratory tract infection
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	1 / 22 (4.55%)	1 / 40 (2.50%)
occurrences all number	1	0	1	1
Urinary tract infection
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	1	0	1
Viral upper respiratory tract infection
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	3	0	1
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Decreased appetite
subjects affected / exposed	2 / 20 (10.00%)	2 / 24 (8.33%)	1 / 22 (4.55%)	1 / 40 (2.50%)
occurrences all number	3	8	1	2
Hypercholesterolaemia
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Hyperuricaemia
subjects affected / exposed	1 / 20 (5.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	1	0	0	0
Hypokalaemia
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	1	0	1
Hypoglycaemia
subjects affected / exposed	0 / 20 (0.00%)	1 / 24 (4.17%)	0 / 22 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	1	0	0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 20 (0.00%)	0 / 24 (0.00%)	0 / 22 (0.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	1

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Were there any global substantial amendments to the protocol? No

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.

As a consequence of the decision to stop the study, not all data are available for a full final analysis as originally planned. Analyses are merely descriptive and the results are presented as an abridged study report.

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Clinical trials

Clinical Trial Results: An open, dose-escalation Phase I/II study to assess the safety, immunogenicity and clinical activity of recPRAME + AS15 Antigen-Specific Cancer Immunotherapeutic as first-line treatment of patients with PRAME-positive metastatic melanoma

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of patients with dose-limiting toxicity (Phase I)

Primary: Number of patients with dose-limiting toxicity (Phase I)

Primary: Percentage of patients with anti-PReferentially expressed Antigen of MElanoma (Anti-PRAME) humoral immune response (Phase I)

Primary: Percentage of patients with anti-PReferentially expressed Antigen of MElanoma (Anti-PRAME) humoral immune response (Phase I)

Primary: Number of patients with best overall response to study treatment (Phase II)

Primary: Number of patients with best overall response to study treatment (Phase II)

Secondary: Number of patients with any unsolicited adverse events (AEs), by maximum grading

Secondary: Number of patients with any unsolicited adverse events (AEs), by maximum grading

Secondary: Number of patients with Serious Adverse Events (SAEs), by maximum grading

Secondary: Number of patients with Serious Adverse Events (SAEs), by maximum grading

Secondary: Number of patients with laboratory abnormalities versus baseline, by maximum grading

Secondary: Number of patients with laboratory abnormalities versus baseline, by maximum grading

Secondary: Number of patients with laboratory abnormalities versus baseline, by maximum grading

Secondary: Number of patients with laboratory abnormalities versus baseline, by maximum grading

Secondary: Number of patients with hematological and biochemical abnormalities versus baseline, by maximum grading

Secondary: Number of patients with hematological and biochemical abnormalities versus baseline, by maximum grading

Secondary: Number of patients with laboratory hematological and biochemical abnormalities versus baseline, by maximum grading

Secondary: Number of patients with laboratory hematological and biochemical abnormalities versus baseline, by maximum grading

Secondary: Number of patients with laboratory hematological and biochemical abnormalities versus baseline, by maximum grading

Secondary: Number of patients with laboratory hematological and biochemical abnormalities versus baseline, by maximum grading

Secondary: Number of patients with abnormal hematological and biochemical results versus baseline, by maximum grading

Secondary: Number of patients with abnormal hematological and biochemical results versus baseline, by maximum grading

Secondary: Number of patients with abnormal hematological and biochemical results versus baseline, by maximum grading

Secondary: Number of patients with abnormal hematological and biochemical results versus baseline, by maximum grading

Secondary: Percentage of patients with anti-PRAME cellular (T-cell) response (Phase I)

Secondary: Percentage of patients with anti-PRAME cellular (T-cell) response (Phase I)

Secondary: Number of subjects with anti-PRAME humoral immune response (Phase I & II)

Secondary: Number of subjects with anti-PRAME humoral immune response (Phase I & II)

Secondary: Number of subjects with best overall response, including Mixed Response (MxR) and Slow Progressive Disease (SPD) criteria (Phase I & II)

Secondary: Number of subjects with best overall response, including Mixed Response (MxR) and Slow Progressive Disease (SPD) criteria (Phase I & II)

Secondary: The anti-Protein D humoral response (Phase I)

Secondary: The anti-Protein D humoral response (Phase I)

Secondary: The anti-Cytosine Phosphate Guanosine oligodeoxynucleotide (CpG) humoral response (Phase I & II)

Secondary: The anti-Cytosine Phosphate Guanosine oligodeoxynucleotide (CpG) humoral response (Phase I & II)

Secondary: Time to treatment failure, progression free survival, overall survival and duration of response (Phase I & II)

Secondary: Time to treatment failure, progression free survival, overall survival and duration of response (Phase I & II)

Secondary: Duration of response for patients with CR, PR and SD or SD/PR status (Phase II)

Secondary: Duration of response for patients with CR, PR and SD or SD/PR status (Phase II)

Secondary: Number of subjects with stable disease (SD), progressive disease (PD), mixed response (MR) (Phase I & II)

Secondary: Number of subjects with stable disease (SD), progressive disease (PD), mixed response (MR) (Phase I & II)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An open, dose-escalation Phase I/II study to assess the safety, immunogenicity and clinical activity of recPRAME + AS15 Antigen-Specific Cancer Immunotherapeutic as first-line treatment of patients with PRAME-positive metastatic melanoma