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Clinical Trial Results:
A Phase 1/2 Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 using the Intra-patient Escalation Dosing Regimen in Patients with Advanced Uveal Melanoma

Summary
EudraCT number	2015-004222-34
Trial protocol	GB DE ES
Global end of trial date	17 Oct 2022

Results information
Results version number	v1(current)
This version publication date	20 May 2023
First version publication date	20 May 2023
Other versions

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

IMCgp100-102

ISRCTN number

US NCT number

NCT02570308

WHO universal trial number (UTN)

Sponsor organisation name

Immunocore Ltd.

Sponsor organisation address

92 Park Drive, Milton Park, Abindgon, Oxfordshire, United Kingdom, OX14 4RY

Public contact

Nicola McKelvie, Immunocore Ltd., +44 1235438600, nicola.mckelvie@immunocore.com.com

Scientific contact

Nicola McKelvie, Immunocore Ltd., +44 1235438600, nicola.mckelvie@immunocore.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

20 Mar 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

20 Mar 2020

Global end of trial reached?

Yes

Global end of trial date

17 Oct 2022

Was the trial ended prematurely?

Main objective of the trial

IMCgp100-102 is a Phase I/II study of the weekly intra-patient escalation dose regimen with IMCgp100 as a single agent in participants with metastatic uveal melanoma (mUM). According to this regimen, all participants in the trial received 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW) and then a dose escalation commenced at the third weekly dose at C1D15. The Phase I testing of the intra-patient escalation dosing regimen is designed to achieve a higher exposure and maximal plasma concentration of IMCgp100 after doses at Cycle 1 Day 15 (C1D15) and thereafter. The Phase I portion of the study was a standard 3+3 dose escalation design. The recommended Phase II dose of the intra-patient escalation dose regimen (RP2D-IE) was identified and expansion cohorts in metastatic uveal melanoma was accrued based on prior therapy.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice (GCP) standards and applicable regulations regarding ethical use of human subjects in medical research.

Background therapy

Evidence for comparator

Actual start date of recruitment

29 Feb 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 19

Country: Number of subjects enrolled

Germany: 10

Country: Number of subjects enrolled

Spain: 9

Country: Number of subjects enrolled

United Kingdom: 17

Country: Number of subjects enrolled

United States: 91

Worldwide total number of subjects

146

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

Adult participants with metastatic Stage 4 uveal melanoma (HLA-A*0201 subtype) with any prior systemic therapy were recruited.

Screening details

Participants were enrolled at study centers located in Canada, Germany, Spain, United Kingdom, and United States.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Blinding implementation details

This was an open-label study.

Are arms mutually exclusive

Yes

Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp

Arm description

Fixed low doses of 20 mcg tebentafusp at Cycle 1 Day 1 (C1D1) and 30 mcg at Cycle 1 Day 8 (C1D8), followed by weekly (QW) 54 mcg dose administered intravenously at Cycle 1 Day 15 (C1D15) and beyond (each cycle is 28 days).

Arm type

Experimental

Investigational medicinal product name

IMCgp100

Investigational medicinal product code

Other name

Tebentafusp, Kimmtrak

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3.

Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp

Arm description

Fixed low doses of 20 mcg tebentafusp at Cycle 1 Day 1 (C1D1) and 30 mcg at Cycle 1 Day 8 (C1D8), followed by weekly (QW) 64 mcg dose administered intravenously at Cycle 1 Day 15 (C1D15) and beyond (each cycle is 28 days).

Arm type

Experimental

Investigational medicinal product name

IMCgp100

Investigational medicinal product code

Other name

Tebentafusp, Kimmtrak

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3.

Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp

Arm description

Fixed low doses of 20 mcg tebentafusp at Cycle 1 Day 1 (C1D1) and 30 mcg at Cycle 1 Day 8 (C1D8), followed by weekly (QW) 73 mcg dose administered intravenously at Cycle 1 Day 15 (C1D15) and beyond (each cycle is 28 days).

Arm type

Experimental

Investigational medicinal product name

IMCgp100

Investigational medicinal product code

Other name

Tebentafusp, Kimmtrak

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3.

Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp

Arm description

Fixed low doses of 20 mcg tebentafusp at Cycle 1 Day 1 (C1D1) and 30 mcg at Cycle 1 Day 8 (C1D8), followed by weekly (QW) 68 mcg dose administered intravenously at Cycle 1 Day 15 (C1D15) and beyond (each cycle is 28 days).

Arm type

Experimental

Investigational medicinal product name

IMCgp100

Investigational medicinal product code

Other name

Tebentafusp, Kimmtrak

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3.

Phase 2 Dose Expansion: 68 mcg Tebentafusp

Arm description

Arm type

Experimental

Investigational medicinal product name

IMCgp100

Investigational medicinal product code

Other name

Tebentafusp, Kimmtrak

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3.

Number of subjects in period 1	Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp	Phase 2 Dose Expansion: 68 mcg Tebentafusp
Started	3	6	4	6	127
Completed	2	1	0	2	53
Not completed	1	5	4	4	74
Consent withdrawn by subject	-	-	-	-	1
Death	1	5	4	4	69
Unspecified	-	-	-	-	2
Lost to follow-up	-	-	-	-	2

Baseline characteristics

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Reporting group title

Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp

Reporting group description

Reporting group title

Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp

Reporting group description

Reporting group title

Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp

Reporting group description

Reporting group title

Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp

Reporting group description

Reporting group title

Phase 2 Dose Expansion: 68 mcg Tebentafusp

Reporting group description

Reporting group values	Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp	Phase 2 Dose Expansion: 68 mcg Tebentafusp	Total
Number of subjects	3	6	4	6	127	146
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0
Adults (18-64 years)	2	4	2	4	120	132
From 65-84 years	1	2	2	2	6	13
85 years and over	0	0	0	0	1	1
Age continuous
Units: years
arithmetic mean (standard deviation)	61.3 ± 6.03	54.7 ± 11.99	56.5 ± 18.41	55.8 ± 9.24	56.5 ± 11.37	-
Gender categorical
Units: Subjects
Female	2	3	2	3	64	74
Male	1	3	2	3	63	72
Race
Units: Subjects
White	3	6	4	6	126	145
Other	0	0	0	0	1	1
Ethnicity
Units: Subjects
Hispanic or Latino	0	1	0	0	4	5
Not Hispanic or Latino	3	5	4	6	123	141

Subject analysis set title

Phase 1 Dose Escalation

Subject analysis set type

Per protocol

Subject analysis set description

Fixed low doses of 20 mcg tebentafusp at Cycle 1 Day 1 (C1D1) and 30 mcg at Cycle 1 Day 8 (C1D8), followed by weekly (QW) doses per cohort administered intravenously at Cycle 1 Day 15 (C1D15) and beyond (each cycle is 28 days).

Subject analysis sets values	Phase 1 Dose Escalation
Number of subjects	19
Age categorical
Units: Subjects
In utero	0
Preterm newborn infants (gestational age < 37 wks)	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	12
From 65-84 years	7
85 years and over	0
Age continuous
Units: years
arithmetic mean (standard deviation)	±
Gender categorical
Units: Subjects
Female
Male
Race
Units: Subjects
White
Other
Ethnicity
Units: Subjects
Hispanic or Latino
Not Hispanic or Latino

End points

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Reporting group title

Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp

Reporting group description

Reporting group title

Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp

Reporting group description

Reporting group title

Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp

Reporting group description

Reporting group title

Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp

Reporting group description

Reporting group title

Phase 2 Dose Expansion: 68 mcg Tebentafusp

Reporting group description

Subject analysis set title

Phase 1 Dose Escalation

Subject analysis set type

Per protocol

Subject analysis set description

Primary: Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1

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End point title

Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1 ^[1] ^[2]

End point description

Number of participants with a dose limiting toxicity, defined as an adverse event (AE) or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment and meets any of the pre-specified criteria. The Safety Analysis Set (SAS) included all participants who received at least 1 full or partial dose of tebentafusp.

End point type

Primary

End point timeframe

Up to 49 months

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: Per protocol, only descriptive statistics are presented.
[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: Per protocol, only descriptive statistics are presented.

End point values	Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp
Number of subjects analysed	3	6	4	6
Units: Participants	0	1	2	0

No statistical analyses for this end point

Primary: Objective Response Rate in Phase 2

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End point title

Objective Response Rate in Phase 2 ^[3] ^[4]

End point description

Objective response rate (ORR) is defined as the percentage of participants with measurable disease with at least 1 visit response of complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an independent central review (ICR). The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline. The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp.

End point type

Primary

End point timeframe

Up to 38 months

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: Per protocol, only descriptive statistics are presented.
[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: Per protocol, only descriptive statistics are presented.

End point values	Phase 2 Dose Expansion: 68 mcg Tebentafusp
Number of subjects analysed	127
Units: Percentage of participants
number (confidence interval 95%)	4.7 (1.8 to 10.0)

No statistical analyses for this end point

Secondary: Objective Response Rate in Phase 1

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End point title

Objective Response Rate in Phase 1

End point description

ORR is defined as the percentage of participants with measurable disease with at least 1 visit response of CR or PR that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an investigator. The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline. The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.

End point type

Secondary

End point timeframe

Up to 49 months

End point values	Phase 1 Dose Escalation
Number of subjects analysed	19
Units: Percentage of participants
number (confidence interval 95%)	15.8 (3.4 to 39.6)

No statistical analyses for this end point

Secondary: Progression-free Survival

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End point title

Progression-free Survival ^[5]

End point description

Progression-free survival is defined as the time in months from first dose of study drug until the date of disease progression or death (by any cause in the absence of disease progression) as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2. The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.

End point type

Secondary

End point timeframe

Up to 49 months

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, only descriptive statistics are presented.

End point values	Phase 2 Dose Expansion: 68 mcg Tebentafusp	Phase 1 Dose Escalation
Number of subjects analysed	127	19
Units: Months
median (confidence interval 95%)	2.8 (2.0 to 3.7)	7.4 (1.2 to 14.8)

No statistical analyses for this end point

Secondary: Disease Control Rate

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End point title

Disease Control Rate ^[6]

End point description

Disease control rate (DCR) is defined as the percentage of participants with a best overall response of CR or PR or stable disease (SD) recorded at least 24 weeks (± 1 week) after commencement of study drug and prior to any progressive disease (PD) event, as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2. The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.

End point type

Secondary

End point timeframe

24 weeks

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: Per protocol, only descriptive statistics are presented.

End point values	Phase 2 Dose Expansion: 68 mcg Tebentafusp	Phase 1 Dose Escalation
Number of subjects analysed	127	19
Units: Percentage of participants
number (confidence interval 95%)	22.8 (15.9 to 31.1)	47.4 (24.4 to 71.1)

No statistical analyses for this end point

Secondary: Duration of Response

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End point title

Duration of Response ^[7]

End point description

Duration of response (DOR) is defined as the time in months from the date of first documented objective response (CR or PR) until the date of documented disease progression or death by any cause in the absence of disease progression as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2. The analysis population included all participants who received at least 1 full or partial dose of tebentafusp and who achieved a response. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.

End point type

Secondary

End point timeframe

Up to 49 months

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, only descriptive statistics are presented.

End point values	Phase 2 Dose Expansion: 68 mcg Tebentafusp	Phase 1 Dose Escalation
Number of subjects analysed	6	3
Units: Months
median (confidence interval 95%)	8.706 (5.552 to 24.542)	7.425 (3.713 to 9999)

No statistical analyses for this end point

Secondary: Time to Response

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End point title

Time to Response ^[8]

End point description

Time to response (TTR) is defined as the time in months from the date of first dose of study drug until the date of first documented objective response as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2. The analysis population included all participants who received at least 1 full or partial dose of tebentafusp and who achieved a response. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.

End point type

Secondary

End point timeframe

Up to 49 months

Notes
[8] - 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: Per protocol, only descriptive statistics are presented.

End point values	Phase 2 Dose Expansion: 68 mcg Tebentafusp	Phase 1 Dose Escalation
Number of subjects analysed	6	3
Units: Months
arithmetic mean (standard deviation)	7.0 ± 6.9	5.5 ± 1.8

No statistical analyses for this end point

Secondary: Overall Survival

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End point title

Overall Survival ^[9]

End point description

Overall survival (OS) is defined as the time in months from the date of first dose of study drug until death due to any cause in general. The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.

End point type

Secondary

End point timeframe

Up to 49 months

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: Per protocol, only descriptive statistics are presented.

End point values	Phase 2 Dose Expansion: 68 mcg Tebentafusp	Phase 1 Dose Escalation
Number of subjects analysed	127	19
Units: Months
median (confidence interval 95%)	16.8 (12.9 to 21.3)	29.6 (10.9 to 42.2)

No statistical analyses for this end point

Secondary: Minor Response Rate

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End point title

Minor Response Rate ^[10]

End point description

Rate of minor response (or better) is defined as the proportion of participants with a confirmed CR, PR, or minor response (MinR) as assessed by RECIST v1.1 by the investigator for Phase 1 or ICR for Phase 2, where MinR is a reduction from baseline in sum of diameters between 10%-29%. The sum of diameters is defined as per RECIST v1.1 as the sum of longest diameters or short axis of target lesions (mm). The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.

End point type

Secondary

End point timeframe

Up to 49 months

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: Per protocol, only descriptive statistics are presented.

End point values	Phase 2 Dose Expansion: 68 mcg Tebentafusp	Phase 1 Dose Escalation
Number of subjects analysed	127	19
Units: Percentage of participants
number (confidence interval 95%)	11.0 (6.2 to 17.8)	26.3 (9.1 to 51.2)

No statistical analyses for this end point

Secondary: Number of Participants With Treatment Dose Interruptions or Reductions

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End point title

Number of Participants With Treatment Dose Interruptions or Reductions

End point description

Tolerability of study treatment was assessed by summarizing the number of participants with dose interruptions or reductions that occurred during the treatment period. The Safety Analysis Set (SAS) included all participants who received at least 1 full or partial dose of tebentafusp.

End point type

Secondary

End point timeframe

Up to 49 months

End point values	Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp	Phase 2 Dose Expansion: 68 mcg Tebentafusp
Number of subjects analysed	3	6	3	4	127
Units: Participants	2	4	3	4	49

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp

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End point title

Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp ^[11]

End point description

Area under the plasma concentration-time curve (AUC) in dose escalation cohorts. All participants who received at least 1 full or partial dose of tebentafusp and with detectable serum concentrations are included.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose

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: Per protocol, only descriptive statistics are presented.

End point values	Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp
Number of subjects analysed	3	6	4	6
Units: hr*pg/mL
geometric mean (standard deviation)
Cycle 1 Day 1	28550 ± 27.0	36530 ± 23.3	32920 ± 18.2	33030 ± 16.5
Cycle 1 Day 15	81310 ± 33.7	98660 ± 34.8	106800 ± 11.6	109800 ± 23.3

No statistical analyses for this end point

Secondary: Maximum plasma concentration (Cmax) of Tebentafusp

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End point title

Maximum plasma concentration (Cmax) of Tebentafusp ^[12]

End point description

The maximum observed plasma drug concentration after single dose administration in dose escalation cohorts. All participants who received at least 1 full or partial dose of tebentafusp and with detectable serum concentrations are included.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose

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: Per protocol, only descriptive statistics are presented.

End point values	Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp
Number of subjects analysed	3	6	4	6
Units: pg/mL
geometric mean (standard deviation)
Cycle 1 Day 1	3050 ± 15.1	3294 ± 22.7	3041 ± 21.7	3640 ± 23.3
Cycle 1 Day 15	8885 ± 17.2	9523 ± 23.0	11300 ± 11.7	11520 ± 25.8

No statistical analyses for this end point

Secondary: Time to Maximum Plasma Concentration (Tmax) of Tebentafusp

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End point title

Time to Maximum Plasma Concentration (Tmax) of Tebentafusp ^[13]

End point description

The Tmax of tebentafusp in the phase 1 dose escalation cohorts is reported. All participants who received at least 1 full or partial dose of tebentafusp and with detectable serum concentrations are included.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose

Notes
[13] - 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: Per protocol, only descriptive statistics are presented.

End point values	Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp
Number of subjects analysed	3	6	4	6
Units: Hours
median (full range (min-max))
Cycle 1 Day 1	0.50 (0.50 to 0.50)	0.50 (0.50 to 0.50)	0.50 (0.50 to 0.50)	0.50 (0.50 to 0.50)
Cycle 1 Day 15	0.50 (0.50 to 0.50)	0.50 (0.50 to 0.50)	0.50 (0.50 to 0.50)	0.50 (0.50 to 0.50)

No statistical analyses for this end point

Secondary: Apparent terminal plasma half-life (t½) of tebentafusp

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End point title

Apparent terminal plasma half-life (t½) of tebentafusp ^[14]

End point description

The apparent t½ of tebentafusp is reported in phase 1 dose escalation cohorts. All participants who received at least 1 full or partial dose of tebentafusp and with detectable serum concentrations are included.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose

Notes
[14] - 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: Per protocol, only descriptive statistics are presented.

End point values	Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp
Number of subjects analysed	3	6	4	6
Units: Hours
median (full range (min-max))
Cycle 1 Day 1	6.635 (5.40 to 6.67)	7.591 (6.03 to 11.3)	6.442 (5.82 to 7.63)	6.273 (5.59 to 10.1)
Cycle 1 Day 15	6.897 (6.78 to 8.03)	7.532 (6.57 to 10.5)	7.519 (6.36 to 9.24)	7.488 (5.70 to 11.9)

No statistical analyses for this end point

Secondary: Percentage of Participants With Anti-IMCgp100 Antibody Formation

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End point title

Percentage of Participants With Anti-IMCgp100 Antibody Formation

End point description

The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp and with evaluable data; two participants were excluded from ADA evaluation due to lack of sampling after dosing.

End point type

Secondary

End point timeframe

Up to 49 months

End point values	Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp	Phase 2 Dose Expansion: 68 mcg Tebentafusp
Number of subjects analysed	3	6	4	6	125
Units: Percentage of participants
number (not applicable)	66.7	16.7	25.0	33.3	33.6

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to 49 months

Adverse event reporting additional description

All treated participants are included.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp

Reporting group description

Reporting group title

Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp

Reporting group description

Reporting group title

Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp

Reporting group description

Reporting group title

Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp

Reporting group description

Reporting group title

Phase 2 Dose Expansion: 68 mcg Tebentafusp

Reporting group description

Serious adverse events	Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp	Phase 2 Dose Expansion: 68 mcg Tebentafusp
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 3 (66.67%)	2 / 6 (33.33%)	3 / 4 (75.00%)	3 / 6 (50.00%)	42 / 127 (33.07%)
number of deaths (all causes)	1	5	4	4	69
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Embolism
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive crisis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Multiple organ system dysfunction syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	9 / 127 (7.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Cytokine release syndrome
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 6 (16.67%)	4 / 127 (3.15%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnea
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary edema
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Confusional state
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	3 / 127 (2.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General physical condition decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Infusion-related reaction
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Platelet count decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Left ventricular dysfunction
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sinus tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infarction
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Aphasia
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hemorrhage intracranial
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal cord compression
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhea
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Biliary colic
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperbilirubinemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 127 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Jaundice cholestatic
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash maculopapular
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 127 (2.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bone pain
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Anal abscess
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis infective
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Biliary tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 127 (2.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypophosphatemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp	Phase 2 Dose Expansion: 68 mcg Tebentafusp
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	6 / 6 (100.00%)	4 / 4 (100.00%)	6 / 6 (100.00%)	127 / 127 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor inflammation
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	3	0	0	0	0
Tumor pain
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	8 / 127 (6.30%)
occurrences all number	3	4	0	0	11
Peripheral sensory neuropathy
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	2 / 4 (50.00%)	0 / 6 (0.00%)	7 / 127 (5.51%)
occurrences all number	0	2	3	0	9
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	1	0	0	0
Flushing
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	16 / 127 (12.60%)
occurrences all number	0	0	0	2	20
Hot flush
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 6 (16.67%)	14 / 127 (11.02%)
occurrences all number	0	2	0	2	26
Hypertension
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	18 / 127 (14.17%)
occurrences all number	0	0	1	1	53
Hypotension
subjects affected / exposed	3 / 3 (100.00%)	4 / 6 (66.67%)	2 / 4 (50.00%)	5 / 6 (83.33%)	53 / 127 (41.73%)
occurrences all number	8	5	4	10	115
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	9 / 127 (7.09%)
occurrences all number	0	0	0	0	20
Chest pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences all number	0	5	0	0	2
Chills
subjects affected / exposed	2 / 3 (66.67%)	3 / 6 (50.00%)	4 / 4 (100.00%)	5 / 6 (83.33%)	84 / 127 (66.14%)
occurrences all number	3	14	48	20	282
Diverticulitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 127 (0.00%)
occurrences all number	0	0	0	1	0
Edema peripheral
subjects affected / exposed	3 / 3 (100.00%)	5 / 6 (83.33%)	3 / 4 (75.00%)	5 / 6 (83.33%)	44 / 127 (34.65%)
occurrences all number	3	6	12	7	86
Face edema
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	2 / 6 (33.33%)	78 / 127 (61.42%)
occurrences all number	0	2	4	4	134
Facial pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	0	0	0	1	2
Fatigue
subjects affected / exposed	2 / 3 (66.67%)	5 / 6 (83.33%)	4 / 4 (100.00%)	6 / 6 (100.00%)	78 / 127 (61.42%)
occurrences all number	9	16	6	21	134
Feeling hot
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	1	0	0	0
Fungal skin infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 127 (0.79%)
occurrences all number	0	0	0	1	1
Gait disturbance
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Generalized edema
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	8 / 127 (6.30%)
occurrences all number	0	0	0	0	12
Hyperbilirubinemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 4 (50.00%)	1 / 6 (16.67%)	10 / 127 (7.87%)
occurrences all number	0	0	2	1	16
Impaired healing
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	1	1	0	0
Infusion site hematoma
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	1	0	0	1
Localized infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 127 (0.00%)
occurrences all number	0	0	0	1	0
Malaise
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 6 (16.67%)	9 / 127 (7.09%)
occurrences all number	0	4	0	1	10
Nodule
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	2	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	4 / 127 (3.15%)
occurrences all number	0	1	2	0	4
Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	10 / 127 (7.87%)
occurrences all number	0	0	0	0	13
Peripheral swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 127 (0.79%)
occurrences all number	0	0	0	1	1
Pyrexia
subjects affected / exposed	3 / 3 (100.00%)	6 / 6 (100.00%)	3 / 4 (75.00%)	6 / 6 (100.00%)	103 / 127 (81.10%)
occurrences all number	15	16	16	21	417
Temperature regulation disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Immune system disorders
Cytokine release syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	10 / 127 (7.87%)
occurrences all number	0	0	0	0	45
Reproductive system and breast disorders
Breast pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Vulvovaginal dryness
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	2	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 3 (33.33%)	2 / 6 (33.33%)	0 / 4 (0.00%)	5 / 6 (83.33%)	29 / 127 (22.83%)
occurrences all number	3	8	0	9	49
Dysphonia
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	1	0	0	0
Dyspnea
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	2 / 4 (50.00%)	2 / 6 (33.33%)	24 / 127 (18.90%)
occurrences all number	0	3	4	6	34
Hiccups
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	1	0	0	0
Hypoxia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	4 / 127 (3.15%)
occurrences all number	0	0	2	1	4
Nasal congestion
subjects affected / exposed	1 / 3 (33.33%)	3 / 6 (50.00%)	2 / 4 (50.00%)	1 / 6 (16.67%)	10 / 127 (7.87%)
occurrences all number	4	6	4	4	13
Oropharyngeal pain
subjects affected / exposed	1 / 3 (33.33%)	2 / 6 (33.33%)	0 / 4 (0.00%)	1 / 6 (16.67%)	13 / 127 (10.24%)
occurrences all number	2	3	0	1	16
Pleuritic pain
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	2	0	0	0	1
Productive cough
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 6 (16.67%)	3 / 127 (2.36%)
occurrences all number	0	3	3	1	4
Pulmonary congestion
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences all number	0	2	0	0	2
Pulmonary edema
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	1	0	0	1
Pulmonary embolism
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 127 (2.36%)
occurrences all number	0	1	0	0	3
Rhinitis allergic
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	3 / 127 (2.36%)
occurrences all number	0	0	0	1	4
Rhinorrhea
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	7 / 127 (5.51%)
occurrences all number	0	0	0	0	8
Sinus pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 127 (0.79%)
occurrences all number	0	0	0	3	1
Upper-airway cough syndrome
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	1	1	1	1	2
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	13 / 127 (10.24%)
occurrences all number	0	1	1	0	13
Confusional state
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	8 / 127 (6.30%)
occurrences all number	1	1	0	0	13
Depressed mood
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 127 (0.00%)
occurrences all number	0	0	0	1	0
Depression
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	6 / 127 (4.72%)
occurrences all number	0	1	1	0	6
Insomnia
subjects affected / exposed	2 / 3 (66.67%)	3 / 6 (50.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	20 / 127 (15.75%)
occurrences all number	2	3	0	1	23
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	2 / 4 (50.00%)	1 / 6 (16.67%)	19 / 127 (14.96%)
occurrences all number	0	2	3	1	33
Amylase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	7 / 127 (5.51%)
occurrences all number	0	0	0	1	8
Aspartate aminotransferase increased
subjects affected / exposed	1 / 3 (33.33%)	2 / 6 (33.33%)	2 / 4 (50.00%)	0 / 6 (0.00%)	23 / 127 (18.11%)
occurrences all number	1	6	3	0	36
Blood alklaline phosphatase increased
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	3 / 6 (50.00%)	13 / 127 (10.24%)
occurrences all number	0	5	0	3	19
Blood cholesterol increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	0	1	0	1
Blood creatinine increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	4 / 127 (3.15%)
occurrences all number	0	0	0	1	4
Cardiac murmur
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	1	0	0	0	0
Lipase increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	12 / 127 (9.45%)
occurrences all number	0	1	1	0	19
Weight decreased
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	1 / 6 (16.67%)	20 / 127 (15.75%)
occurrences all number	0	2	1	1	20
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	2	0	0	1
Contusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 4 (50.00%)	0 / 6 (0.00%)	5 / 127 (3.94%)
occurrences all number	0	0	2	0	5
Fall
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	7 / 127 (5.51%)
occurrences all number	1	0	0	0	8
Infusion related reaction
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences all number	1	1	0	0	2
Ligament injury
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	1	0	0	0	0
Procedural pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	8 / 127 (6.30%)
occurrences all number	0	0	0	0	8
Scratch
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	1	0	0	0	0
Skin abrasion
subjects affected / exposed	0 / 3 (0.00%)	3 / 6 (50.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	5 / 127 (3.94%)
occurrences all number	0	11	5	1	11
Skin laceration
subjects affected / exposed	0 / 3 (0.00%)	3 / 6 (50.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	0	6	0	1	3
Sunburn
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 4 (50.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences all number	0	0	2	0	4
Wound
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	2	0	0	1
Cardiac disorders
Cardiomegaly
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Hypertensive heart disease
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Palpitations
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Pericardial effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Sinus tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	12 / 127 (9.45%)
occurrences all number	0	0	0	3	15
Tachycardia
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	15 / 127 (11.81%)
occurrences all number	1	1	0	0	22
Nervous system disorders
Aphasia
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	1	0	0	0	1
Ataxia
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	1	0	0	0
Cerebral arteriosclerosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Disturbance in attention
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	1	0	0	0	0
Dizziness
subjects affected / exposed	1 / 3 (33.33%)	2 / 6 (33.33%)	2 / 4 (50.00%)	3 / 6 (50.00%)	21 / 127 (16.54%)
occurrences all number	1	4	4	3	25
Dysgeusia
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	12 / 127 (9.45%)
occurrences all number	0	1	2	0	13
Headache
subjects affected / exposed	2 / 3 (66.67%)	3 / 6 (50.00%)	2 / 4 (50.00%)	4 / 6 (66.67%)	42 / 127 (33.07%)
occurrences all number	3	6	2	12	91
Memory impairment
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	3 / 4 (75.00%)	1 / 6 (16.67%)	1 / 127 (0.79%)
occurrences all number	0	1	3	1	1
Neuropathy peripheral
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 127 (2.36%)
occurrences all number	1	0	0	0	3
Paresthesia
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	2 / 4 (50.00%)	1 / 6 (16.67%)	10 / 127 (7.87%)
occurrences all number	1	4	3	2	15
Syncope
subjects affected / exposed	2 / 3 (66.67%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 127 (2.36%)
occurrences all number	2	0	0	0	3
Blood and lymphatic system disorders
Anemia
subjects affected / exposed	1 / 3 (33.33%)	2 / 6 (33.33%)	1 / 4 (25.00%)	2 / 6 (33.33%)	17 / 127 (13.39%)
occurrences all number	1	2	1	2	21
Lymphadenopathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	0	1	0	1
Lymphopenia
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	4 / 127 (3.15%)
occurrences all number	1	1	0	0	4
Neutropenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	0	0	0	1	3
Ear and labyrinth disorders
Ear discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	0	2	0	1
Ear pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 127 (0.79%)
occurrences all number	0	1	0	2	1
Hyperacusis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 127 (0.00%)
occurrences all number	0	0	0	1	0
Otorrhea
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Parasthesia ear
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	1	0	0	0	0
Tinnitus
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	0	1	0	1
Vertigo
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	3 / 127 (2.36%)
occurrences all number	1	0	0	1	4
Eye disorders
Dry eye
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	9 / 127 (7.09%)
occurrences all number	0	3	0	0	12
Eye inflammation
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 127 (0.00%)
occurrences all number	0	1	0	1	0
Eyelash hypopigmentation
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences all number	0	1	0	0	2
Lacrimation increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 6 (16.67%)	4 / 127 (3.15%)
occurrences all number	0	1	0	1	4
Ocular hyperemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	3 / 127 (2.36%)
occurrences all number	0	0	1	0	3
Periorbital edema
subjects affected / exposed	1 / 3 (33.33%)	4 / 6 (66.67%)	3 / 4 (75.00%)	4 / 6 (66.67%)	34 / 127 (26.77%)
occurrences all number	2	13	9	9	69
Vision blurred
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 4 (25.00%)	2 / 6 (33.33%)	6 / 127 (4.72%)
occurrences all number	1	0	1	2	7
Visual impairment
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	0	1	4	1	2
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	1 / 6 (16.67%)	14 / 127 (11.02%)
occurrences all number	0	2	0	1	16
Abdominal pain
subjects affected / exposed	1 / 3 (33.33%)	4 / 6 (66.67%)	3 / 4 (75.00%)	2 / 6 (33.33%)	45 / 127 (35.43%)
occurrences all number	1	9	7	7	71
Abdominal pain lower
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	0	0	0	2	4
Abdominal pain upper
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 4 (25.00%)	2 / 6 (33.33%)	30 / 127 (23.62%)
occurrences all number	2	0	1	3	45
Constipation
subjects affected / exposed	1 / 3 (33.33%)	3 / 6 (50.00%)	2 / 4 (50.00%)	3 / 6 (50.00%)	30 / 127 (23.62%)
occurrences all number	1	4	5	4	45
Dental caries
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Diarrhea
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	3 / 4 (75.00%)	4 / 6 (66.67%)	33 / 127 (25.98%)
occurrences all number	0	13	7	11	50
Dyspepsia
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	2 / 6 (33.33%)	15 / 127 (11.81%)
occurrences all number	0	2	1	5	21
Dysphagia
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	2	1	1	0	1
Eructation
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	1	0	0	0	1
Gastric ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Gastritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	6 / 127 (4.72%)
occurrences all number	0	0	0	1	6
Gastroesophageal reflux disease
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	16 / 127 (12.60%)
occurrences all number	0	0	1	0	23
Gastrointestinal pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	1	1	0	0
Hemorrhoidal hemorrhage
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	2	0	0	0
Nausea
subjects affected / exposed	2 / 3 (66.67%)	5 / 6 (83.33%)	4 / 4 (100.00%)	5 / 6 (83.33%)	86 / 127 (67.72%)
occurrences all number	7	21	18	14	247
Oral pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences all number	0	1	0	0	2
Rectal hemorrhage
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	2	0	0	0
Vomiting
subjects affected / exposed	0 / 3 (0.00%)	3 / 6 (50.00%)	3 / 4 (75.00%)	4 / 6 (66.67%)	52 / 127 (40.94%)
occurrences all number	0	13	5	11	141
Hepatobiliary disorders
Hepatic failure
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	1	0	0	0
Hepatic pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 4 (50.00%)	1 / 6 (16.67%)	7 / 127 (5.51%)
occurrences all number	0	0	4	1	10
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	3 / 4 (75.00%)	2 / 6 (33.33%)	12 / 127 (9.45%)
occurrences all number	0	0	3	2	12
Blister
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	1	1	0	1	3
Dermatitis acneiform
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	8 / 127 (6.30%)
occurrences all number	1	0	0	1	13
Dermatitis allergic
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	0	0	0	1	3
Dry skin
subjects affected / exposed	1 / 3 (33.33%)	4 / 6 (66.67%)	2 / 4 (50.00%)	5 / 6 (83.33%)	52 / 127 (40.94%)
occurrences all number	1	5	3	9	68
Ephelides
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences all number	0	1	0	0	2
Erythema
subjects affected / exposed	1 / 3 (33.33%)	4 / 6 (66.67%)	3 / 4 (75.00%)	2 / 6 (33.33%)	22 / 127 (17.32%)
occurrences all number	1	20	19	8	33
Generalized erythema
subjects affected / exposed	1 / 3 (33.33%)	3 / 6 (50.00%)	2 / 4 (50.00%)	0 / 6 (0.00%)	20 / 127 (15.75%)
occurrences all number	1	3	4	0	59
Hair color changes
subjects affected / exposed	1 / 3 (33.33%)	2 / 6 (33.33%)	2 / 4 (50.00%)	3 / 6 (50.00%)	34 / 127 (26.77%)
occurrences all number	1	2	2	7	38
Hyperhidrosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	4 / 127 (3.15%)
occurrences all number	0	0	0	1	4
Miiaria
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	1	0	0	0
Nail discoloration
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	1	0	0	0	0
Night sweats
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 6 (16.67%)	3 / 127 (2.36%)
occurrences all number	1	1	0	2	3
Pain of skin
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	3 / 127 (2.36%)
occurrences all number	0	0	2	0	3
Palmar-plantar erythrodysesthesia syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	0	0	0	1	2
Papule
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	9	0	0	1
Photosensitivity reaction
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	0	1	4	1	3
Pruritus
subjects affected / exposed	3 / 3 (100.00%)	4 / 6 (66.67%)	4 / 4 (100.00%)	6 / 6 (100.00%)	87 / 127 (68.50%)
occurrences all number	6	25	18	26	206
Pruritus generalized
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	22 / 127 (17.32%)
occurrences all number	0	1	0	0	70
Psoriasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Purpura
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	1	0	0	0	0
Rash
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	2 / 6 (33.33%)	42 / 127 (33.07%)
occurrences all number	0	1	4	6	88
Rash erythematous
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	6 / 127 (4.72%)
occurrences all number	2	1	1	0	7
Rash generalized
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	30 / 127 (23.62%)
occurrences all number	0	0	1	0	63
Rash macular
subjects affected / exposed	1 / 3 (33.33%)	3 / 6 (50.00%)	2 / 4 (50.00%)	2 / 6 (33.33%)	0 / 127 (0.00%)
occurrences all number	2	9	15	5	0
Rash maculo-papular
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	51 / 127 (40.16%)
occurrences all number	0	0	0	4	121
Rash papular
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 6 (16.67%)	1 / 127 (0.79%)
occurrences all number	0	1	1	1	2
Rash pruritic
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	1 / 6 (16.67%)	5 / 127 (3.94%)
occurrences all number	0	5	12	1	18
Scab
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences all number	0	0	1	0	2
Sensitive skin
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	1	0	0	0
Skin exfoliation
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	28 / 127 (22.05%)
occurrences all number	0	1	0	0	32
Skin fissures
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	1	0	0	1
Skin hyperpigmentation
subjects affected / exposed	1 / 3 (33.33%)	3 / 6 (50.00%)	2 / 4 (50.00%)	0 / 6 (0.00%)	21 / 127 (16.54%)
occurrences all number	1	3	2	0	22
Skin hypopigmentation
subjects affected / exposed	0 / 3 (0.00%)	3 / 6 (50.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	25 / 127 (19.69%)
occurrences all number	0	3	0	4	31
Skin irritation
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	0	1	0	1
Skin lesion
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 6 (16.67%)	6 / 127 (4.72%)
occurrences all number	0	1	0	1	6
Skin mass
subjects affected / exposed	1 / 3 (33.33%)	3 / 6 (50.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	11 / 127 (8.66%)
occurrences all number	2	11	0	1	15
Skin ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 127 (0.00%)
occurrences all number	0	0	0	1	0
Vitiligo
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	7 / 127 (5.51%)
occurrences all number	0	0	0	2	7
Renal and urinary disorders
Chromaturia
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	1	0	0	0
Dysuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	3 / 127 (2.36%)
occurrences all number	0	0	0	2	4
Nocturia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 127 (0.00%)
occurrences all number	0	0	0	1	0
Musculoskeletal and connective tissue disorders
Ligament sprain
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Arthralgia
subjects affected / exposed	1 / 3 (33.33%)	4 / 6 (66.67%)	3 / 4 (75.00%)	1 / 6 (16.67%)	33 / 127 (25.98%)
occurrences all number	1	7	6	2	45
Back pain
subjects affected / exposed	2 / 3 (66.67%)	5 / 6 (83.33%)	4 / 4 (100.00%)	2 / 6 (33.33%)	41 / 127 (32.28%)
occurrences all number	6	24	5	4	57
Bone pain
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 4 (0.00%)	2 / 6 (33.33%)	3 / 127 (2.36%)
occurrences all number	9	5	0	2	3
Flank pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	4 / 127 (3.15%)
occurrences all number	0	0	0	1	5
Muscle tightness
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 127 (0.00%)
occurrences all number	0	0	0	11	0
Muscular weakness
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	0 / 6 (0.00%)	5 / 127 (3.94%)
occurrences all number	0	2	1	0	6
Musculoskeletal chest pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	0 / 6 (0.00%)	6 / 127 (4.72%)
occurrences all number	0	4	2	0	8
Musculoskeletal pain
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	2 / 4 (50.00%)	1 / 6 (16.67%)	12 / 127 (9.45%)
occurrences all number	0	10	2	2	23
Myalgia
subjects affected / exposed	3 / 3 (100.00%)	3 / 6 (50.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	23 / 127 (18.11%)
occurrences all number	5	8	5	3	33
Neck pain
subjects affected / exposed	1 / 3 (33.33%)	2 / 6 (33.33%)	2 / 4 (50.00%)	1 / 6 (16.67%)	11 / 127 (8.66%)
occurrences all number	1	3	3	2	14
Pain in extremity
subjects affected / exposed	1 / 3 (33.33%)	4 / 6 (66.67%)	3 / 4 (75.00%)	2 / 6 (33.33%)	19 / 127 (14.96%)
occurrences all number	1	19	10	3	33
Pain in jaw
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	1	0	0	0	0
Infections and infestations
Nail infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	1	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	13 / 127 (10.24%)
occurrences all number	0	0	0	0	18
Oral herpes
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 6 (0.00%)	3 / 127 (2.36%)
occurrences all number	0	2	0	0	3
Otitis media
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	1	0	0	0	0
Pharyngitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 127 (0.00%)
occurrences all number	0	0	1	0	0
Sinusitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	7 / 127 (5.51%)
occurrences all number	0	0	0	1	7
Skin infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	1	0	0	1
Tinea pedis
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 127 (0.00%)
occurrences all number	0	0	0	2	0
Tooth infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 127 (0.79%)
occurrences all number	0	0	1	0	1
Upper respiratory tract infection
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	11 / 127 (8.66%)
occurrences all number	2	3	2	0	16
Urinary tract infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 6 (16.67%)	16 / 127 (12.60%)
occurrences all number	0	1	0	1	18
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 3 (33.33%)	4 / 6 (66.67%)	0 / 4 (0.00%)	2 / 6 (33.33%)	32 / 127 (25.20%)
occurrences all number	1	4	0	3	45
Dehydration
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	5 / 127 (3.94%)
occurrences all number	0	0	2	0	5
Hyperglycemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	2 / 127 (1.57%)
occurrences all number	0	0	2	0	3
Hyperkalemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	3 / 6 (50.00%)	4 / 127 (3.15%)
occurrences all number	0	2	0	3	4
Hypermagnesemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	0	0	0	1	2
Hypoalbuminemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	5 / 127 (3.94%)
occurrences all number	0	1	0	0	6
Hypocalcemia
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	10 / 127 (7.87%)
occurrences all number	1	2	0	0	13
Hypoglycemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	0	0	0	2	4
Hypokalemia
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	2 / 127 (1.57%)
occurrences all number	1	0	0	1	4
Hypomagnesemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	13 / 127 (10.24%)
occurrences all number	0	0	0	0	22
Hypophosphatemia
subjects affected / exposed	1 / 3 (33.33%)	2 / 6 (33.33%)	0 / 4 (0.00%)	1 / 6 (16.67%)	14 / 127 (11.02%)
occurrences all number	1	2	0	1	25

More information

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Were there any global substantial amendments to the protocol? Yes

08 Dec 2015

Amendment 1 was issued to implement dosing changes in the intra-patient dose-escalation regimen in response to hypotension observed in the ongoing first-in-human (FIH) study.

11 Jan 2016

Amendment 2 was issued to implement monitoring changes for hypotension in the intra-patient dose escalation regimen.

23 May 2016

Amendment 3 was issued to implement a change in the definition of dose limiting toxicity (DLT) with respect to recent observations of transient elevations of hepatic transaminases, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), in patients with uveal melanoma (UM) in the 2 ongoing Phase 1 trials with IMCgp100, the first-in-human (FIH) study (IMCgp100-01) and this UM Phase 1 study.

07 Sep 2016

Amendment 4 was issued to only enroll participants with HLA-A*0201 allele determined centrally.

11 Apr 2017

Amendment 5 was issued to update the nomenclature of the dose levels and the recommended Phase 2 dose (RP2D) of IMCgp100 utilizing the intra-patient escalation.

15 Dec 2017

Amendment 6 was issued primarily to transition the dose expansion cohort of the study to more formal Phase 2 testing in participants with metastatic uveal melanoma who are treated in the second or third line setting in this trial.

26 Nov 2018

Amendment 7 was issued to clarify the interim and final analysis that will be done to assess the efficacy of IMCgp100 in the Phase 2 expansion phase.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase 1/2 Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 using the Intra-patient Escalation Dosing Regimen in Patients with Advanced Uveal Melanoma

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1

Primary: Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1

Primary: Objective Response Rate in Phase 2

Primary: Objective Response Rate in Phase 2

Secondary: Objective Response Rate in Phase 1

Secondary: Objective Response Rate in Phase 1

Secondary: Progression-free Survival

Secondary: Progression-free Survival

Secondary: Disease Control Rate

Secondary: Disease Control Rate

Secondary: Duration of Response

Secondary: Duration of Response

Secondary: Time to Response

Secondary: Time to Response

Secondary: Overall Survival

Secondary: Overall Survival

Secondary: Minor Response Rate

Secondary: Minor Response Rate

Secondary: Number of Participants With Treatment Dose Interruptions or Reductions

Secondary: Number of Participants With Treatment Dose Interruptions or Reductions

Secondary: Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp

Secondary: Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp

Secondary: Maximum plasma concentration (Cmax) of Tebentafusp

Secondary: Maximum plasma concentration (Cmax) of Tebentafusp

Secondary: Time to Maximum Plasma Concentration (Tmax) of Tebentafusp

Secondary: Time to Maximum Plasma Concentration (Tmax) of Tebentafusp

Secondary: Apparent terminal plasma half-life (t½) of tebentafusp

Secondary: Apparent terminal plasma half-life (t½) of tebentafusp

Secondary: Percentage of Participants With Anti-IMCgp100 Antibody Formation

Secondary: Percentage of Participants With Anti-IMCgp100 Antibody Formation

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 1/2 Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 using the Intra-patient Escalation Dosing Regimen in Patients with Advanced Uveal Melanoma