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Clinical Trial Results:
A Phase I/II Open-Label, Multi-center Study of the Safety and Efficacy of IMCnyeso, an HLA-A* 0201-Restricted, NY-ESO-1 and LAGE-1A-specific soluble T Cell Receptor and Anti-CD3 Bi-specific Molecule, as a Single Agent in HLA-A* 0201 Positive Patients With Advanced NY-ESO-1 and/or LAGE-1A Positive Cancer

Summary
EudraCT number	2017-002243-15
Trial protocol	GB
Global end of trial date	10 Jun 2021

Results information
Results version number	v1(current)
This version publication date	10 Mar 2022
First version publication date	10 Mar 2022
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

IMCnyeso-101

ISRCTN number

US NCT number

NCT03515551

WHO universal trial number (UTN)

Sponsor organisation name

Immunocore, Ltd.

Sponsor organisation address

92 Park Drive, Milton Park, Abingdon, United Kingdom, Oxon, OX14 4RY

Public contact

Study Director, Immunocore Ltd., 001 844IMMUNO1, clinicaltrials@immunocore.com

Scientific contact

Study Director, Immunocore Ltd., 001 844IMMUNO1, clinicaltrials@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

10 Jun 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

10 Jun 2021

Was the trial ended prematurely?

Yes

Main objective of the trial

This was planned to be a multi-center, open label, dose finding Phase 1/2 study of single agent IMCnyeso administered in subjects with NY-ESO-1 and/or LAGE-A1 positive tumors. The primary objective of the dose escalation phase (Phase 1) was to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of IMCnyeso in subjects with advanced solid tumors. Preliminary efficacy was to be evaluated in Phase 2. The study was terminated early (prior to initiation of Phase 2) by the Sponsor as a strategic decision (not based on any safety signal).

Protection of trial subjects

This clinical study was designed and was implemented and reported in accordance with the ICH Harmonised Tripartite Guidelines for Good Clinical Practice E6 (R1), with applicable local regulations (including European Directive 2001/20/EC and Unites States Code of Federal Regulations, CFR Title 21), and with the ethical principles laid down in the Declaration of Helsinki (2013).

Background therapy

Evidence for comparator

Actual start date of recruitment

15 Jun 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 10

Country: Number of subjects enrolled

Canada: 3

Country: Number of subjects enrolled

United States: 15

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The sponsor elected to not proceed with the efficacy determining expansion phase (Phase 2) of IMCnyeso-101 for strategic reasons. Phase 2 data were not collected. As of 25 Mar 2021, further enrollment into the Phase 1 dose escalation phase was discontinued and last patient visit was 10 June 2021.

Screening details

There were a total of 28 unique subjects; one subject from the 10 mcg cohort was sequentially enrolled in the 30-100 mcg cohort. Participants who were receiving study drug were allowed to continue treatment until unacceptable toxicity, disease progression, or other reason to discontinue occurred.

Period 1 title

Overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Phase 1: IMCnyeso 3 mcg

Arm description

Single-agent IMCnyeso at 3 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen

Arm type

Experimental

Investigational medicinal product name

IMCnyeso

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects enrolled in this study received treatment with single-agent IMCnyeso dosed weekly on Days 1, 8, 15, and 22 of each 4-week cycle. There were 4 fixed-dose, dose escalation cohorts: 3, 10, 30, and 100 mcg. There were 3 intrapatient dose escalation cohorts: 30-100 mcg, 30-100-180 mcg, and 30-100-300 mcg.

Phase 1: IMCnyeso 10 mcg

Arm description

Single-agent IMCnyeso at 10 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen

Arm type

Experimental

Investigational medicinal product name

IMCnyeso

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Phase 1: IMCnyeso 30 mcg

Arm description

Single-agent IMCnyeso at 30 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen

Arm type

Experimental

Investigational medicinal product name

IMCnyeso

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Phase 1: IMCnyeso 100 mcg

Arm description

Single-agent IMCnyeso at 100 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen

Arm type

Experimental

Investigational medicinal product name

IMCnyeso

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Phase 1: IMCnyeso 30-100 mcg

Arm description

IMCnyeso administered intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using an intrapatient escalation regimen (30 mcg on Cycle 1 Day 1, then 100 mcg starting on Cycle 1 Day 8)

Arm type

Experimental

Investigational medicinal product name

IMCnyeso

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Phase 1: IMCnyeso 30-100-180 mcg

Arm description

IMCnyeso administered intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using an intrapatient escalation regimen (30 mcg on Cycle 1 Day 1, then 100 mcg on Cycle 1 Day 8, then 180 mcg starting on Cycle 1 Day 15)

Arm type

Experimental

Investigational medicinal product name

IMCnyeso

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Phase 1: IMCnyeso 30-100-300 mcg

Arm description

Arm type

Experimental

Investigational medicinal product name

IMCnyeso

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 1	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Started	4	3	5	3	4	4	5
Completed	0	0	0	0	0	0	0
Not completed	4	3	5	3	5	4	5
Consent withdrawn by subject	-	1	-	-	-	-	1
Death	4	1	2	2	2	4	1
Study ended by sponsor	-	-	2	1	3	-	3
Transferred to other arm/group	-	1	-	-	-	-	-
Lost to follow-up	-	-	1	-	-	-	-
Joined	0	0	0	0	1	0	0
Transferred in from other group/arm	-	-	-	-	1	-	-

Baseline characteristics

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Reporting group title

Overall study

Reporting group description

Notes
[1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same.
Justification: One subject from the 10 mcg cohort was sequentially enrolled in the 30-100 mcg cohort; there were a total of 28 unique subjects

Reporting group values	Overall study	Total
Number of subjects	28	28
Age categorical
Units: Subjects
Adults (18-64 years)	23	23
From 65-84 years	5	5
Gender categorical
Units: Subjects
Female	12	12
Male	16	16
Original cancer diagnosis
Units: Subjects
Melanoma	7	7
Synovial sarcoma	20	20
Urothelial carcinoma	1	1
Non-small cell lung cancer	0	0

End points

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Reporting group title

Phase 1: IMCnyeso 3 mcg

Reporting group description

Single-agent IMCnyeso at 3 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen

Reporting group title

Phase 1: IMCnyeso 10 mcg

Reporting group description

Single-agent IMCnyeso at 10 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen

Reporting group title

Phase 1: IMCnyeso 30 mcg

Reporting group description

Single-agent IMCnyeso at 30 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen

Reporting group title

Phase 1: IMCnyeso 100 mcg

Reporting group description

Single-agent IMCnyeso at 100 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen

Reporting group title

Phase 1: IMCnyeso 30-100 mcg

Reporting group description

IMCnyeso administered intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using an intrapatient escalation regimen (30 mcg on Cycle 1 Day 1, then 100 mcg starting on Cycle 1 Day 8)

Reporting group title

Phase 1: IMCnyeso 30-100-180 mcg

Reporting group description

Reporting group title

Phase 1: IMCnyeso 30-100-300 mcg

Reporting group description

Primary: Number of subjects with dose-limiting toxicities

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End point title

Number of subjects with dose-limiting toxicities ^[1]

End point description

Dose-limiting toxicities were defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug that occurs within the evaluation period, from the first dose up until Day 28 after the first dose

End point type

Primary

End point timeframe

Up to 35 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: There are no statistical analyses for descriptive data.

End point values	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Number of subjects analysed	4	3 ^[2]	5	3	5	4	5
Units: Subjects	0	0	0	0	0	0	2

Notes
[2] - 1 subject from the 10 mcg cohort was sequentially enrolled in the 30-100 mcg cohort

No statistical analyses for this end point

Primary: Number of subjects with adverse events

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End point title

Number of subjects with adverse events ^[3]

End point description

Treatment-emergent adverse events are defined as any adverse event (AE) that started after the first dose of study drug up to 30 days after last dose of study drug, including abnormal laboratory values, vital signs, or electrocardiogram results. AE severity is graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03

End point type

Primary

End point timeframe

Up to 35 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: There are no statistical analyses for descriptive data.

End point values	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Number of subjects analysed	4	3	5	3	5	4	5
Units: Subjects
Any treatment-emergent adverse event (TEAE)	4	3	5	3	5	4	5
Any TEAE Grade ≥3	3	1	1	3	3	4	4
Any TEAE leading to death	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Number of subjects with no dose interruptions or reductions

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End point title

Number of subjects with no dose interruptions or reductions ^[4]

End point description

Tolerability of study treatment was assessed by summarizing the number of subjects with no treatment dose interruptions and dose reductions

End point type

Primary

End point timeframe

Up to 35 months

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There are no statistical analyses for descriptive data.

End point values	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Number of subjects analysed	4	3	5	3	5	4	5
Units: Subjects
No dose interruption at any time	2	0	0	2	2	0	0
No dose reduction at any time	4	3	5	3	4	4	3

No statistical analyses for this end point

Secondary: Number of subjects with best overall response

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End point title

Number of subjects with best overall response

End point description

Number of subjects with best overall response, including complete response, partial response, stable disease, and progressive disease, based on local Investigator assessment as defined in RECIST v.1.1. Data were pooled for this analysis due to small sample size per cohort with evaluable data. CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease

End point type

Secondary

End point timeframe

Up to 35 months

End point values	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Number of subjects analysed	4	3	5	3	5	4	5
Units: Subjects
Complete Response	0	0	0	0	0	0	0
Partial Response	0	0	0	0	0	0	0
Stable Disease	0	0	2	0	2	0	1
Progressive Disease	3	3	3	3	3	3	3

No statistical analyses for this end point

Secondary: Progression-free survival

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End point title

Progression-free survival

End point description

Progression-free survival is defined as the time from first dose until the date of objective progression, or death from any cause, whichever occurs first.

End point type

Secondary

End point timeframe

Up to 35 months

End point values	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Number of subjects analysed	4	3	5	3	5	4	5 ^[5]
Units: Months
median (confidence interval 95%)	1.8 (0.7 to 2.4)	1.6 (1.2 to 2.1)	2.1 (1.9 to 7.8)	1.9 (1.3 to 1.9)	2.1 (0.8 to 3.8)	1.8 (0.9 to 2.1)	1.4 (1.0 to 9999)

Notes
[5] - 9999 = not estimable due to insufficient number of events

No statistical analyses for this end point

Secondary: Overall survival

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End point title

Overall survival

End point description

Overall survival is defined as the time (in months) from the date of randomization to the date of death due to any cause.

End point type

Secondary

End point timeframe

Up to 35 months

End point values	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Number of subjects analysed	4	3 ^[6]	5 ^[7]	3 ^[8]	5 ^[9]	4	5 ^[10]
Units: Months
median (confidence interval 95%)	3.3 (2.1 to 5.9)	9999 (2.2 to 9999)	9999 (3.7 to 9999)	9.7 (2.3 to 9999)	9999 (5.2 to 9999)	7.5 (0.9 to 11.7)	9999 (3.7 to 9999)

Notes
[6] - 9999 = not estimable due to insufficient number of events
[7] - 9999 = not estimable due to insufficient number of events
[8] - 9999 = not estimable due to insufficient number of events
[9] - 9999 = not estimable due to insufficient number of events
[10] - 9999 = not estimable due to insufficient number of events

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last)

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End point title

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last)

End point description

End point type

Secondary

End point timeframe

Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15

End point values	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Number of subjects analysed	4	3	4	3	5	4	4 ^[11]
Units: hr*pg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1	12500 ± 6910	17700 ± 14400	132000 ± 44600	295000 ± 72400	182000 ± 180000	78800 ± 32500	127000 ± 53700
Cycle 1 Day 15	7270 ± 4530	29500 ± 35900	149000 ± 70500	301000 ± 223000	497000 ± 260000	611000 ± 330000	142000 ± 9999

Notes
[11] - 9999 = not estimable due to insufficient number of subjects

No statistical analyses for this end point

Secondary: Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax)

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End point title

Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax)

End point description

End point type

Secondary

End point timeframe

Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15

End point values	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Number of subjects analysed	4	3	4	3	5	4	4 ^[12]
Units: pg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1	1130 ± 674	1530 ± 1160	6850 ± 1110	16100 ± 961	6810 ± 5290	3890 ± 932	6710 ± 1380
Cycle 1 Day 15	1090 ± 634	1800 ± 1290	6220 ± 1450	17900 ± 1910	19900 ± 3570	26900 ± 3930	65800 ± 000

Notes
[12] - 9999 = not estimable due to insufficient number of subjects

No statistical analyses for this end point

Secondary: Time to Reach Maximum Plasma Concentration (Tmax)

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End point title

Time to Reach Maximum Plasma Concentration (Tmax)

End point description

End point type

Secondary

End point timeframe

Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15

End point values	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Number of subjects analysed	4	3	4	3	5	4	4 ^[13]
Units: Hours
arithmetic mean (standard deviation)
Cycle 1 Day 1	1.00 ± 0.00	1.00 ± 0.00	1.00 ± 0.00	1.67 ± 1.15	1.00 ± 0.00	1.25 ± 0.50	1.00 ± 0.00
Cycle 1 Day 15	1.00 ± 0.00	1.00 ± 0.00	1.00 ± 0.00	1.00 ± 0.00	1.00 ± 0.00	1.00 ± 0.00	2.00 ± 0.00

Notes
[13] - 000 = not estimable due to insufficient number of subjects

No statistical analyses for this end point

Secondary: Number of Subjects With Anti-IMCnyeso Antibody Formation

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End point title

Number of Subjects With Anti-IMCnyeso Antibody Formation

End point description

Number of subjects with positive treatment-boosted or treatment-induced anti-IMCnyeso antibody titers

End point type

Secondary

End point timeframe

Up to 35 months

End point values	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Number of subjects analysed	4	3	5	3	5	4	5
Units: Subjects	0	0	0	1	0	0	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to 35 months

Adverse event reporting additional description

The Safety Analysis Set includes all subjects who received at least 1 full or partial dose of study drug in Phase 1; the Phase 2 arm was not started and no data were collected. One subject was sequentially enrolled in two cohorts (10 mcg and 30-100 mcg). Events in either cohort are counted once in the total cohort.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

Phase 1: IMCnyeso 3 mcg

Reporting group description

Single-agent IMCnyeso at 3 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen

Reporting group title

Phase 1: IMCnyeso 10 mcg

Reporting group description

Single-agent IMCnyeso at 10 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen

Reporting group title

Phase 1: IMCnyeso 30 mcg

Reporting group description

Single-agent IMCnyeso at 30 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen

Reporting group title

Phase 1: IMCnyeso 100 mcg

Reporting group description

Single-agent IMCnyeso at 100 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen

Reporting group title

Phase 1: IMCnyeso 30-100 mcg

Reporting group description

Single-agent IMCnyeso at 30 mcg intravenously on Cycle 1 Day 1, then 100 mcg weekly intravenously starting on Cycle 1 Day 8 of each 4-week cycle

Reporting group title

Phase 1: IMCnyeso 30-100-180 mcg

Reporting group description

Single-agent IMCnyeso at 30 mcg intravenously on Cycle 1 Day 1, 100 mcg on Cycle 1 Day 8, then 180 mcg weekly intravenously starting on Cycle 1 Day 15 of each 4-week cycle

Reporting group title

Phase 1: IMCnyeso 30-100-300 mcg

Reporting group description

Single-agent IMCnyeso at 30 mcg intravenously on Cycle 1 Day 1, 100 mcg on Cycle 1 Day 8, then 300 mcg weekly intravenously starting on Cycle 1 Day 15 of each 4-week cycle

Serious adverse events	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 4 (75.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	1 / 3 (33.33%)	2 / 5 (40.00%)	3 / 4 (75.00%)	3 / 5 (60.00%)
number of deaths (all causes)	4	1	2	2	2	4	1
number of deaths resulting from adverse events	0	0	0	0	0	0	0
Investigations
Aspartate aminotransferase increased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Overdose
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tracheal obstruction
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypotension
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Sinus tachycardia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Febrile neutropenia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Fatigue
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Cytokine release storm
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intra-abdominal haemorrhage
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatic failure
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epistaxis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Hypoxia
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Muscular haemorrhage
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Lung infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Phase 1: IMCnyeso 3 mcg	Phase 1: IMCnyeso 10 mcg	Phase 1: IMCnyeso 30 mcg	Phase 1: IMCnyeso 100 mcg	Phase 1: IMCnyeso 30-100 mcg	Phase 1: IMCnyeso 30-100-180 mcg	Phase 1: IMCnyeso 30-100-300 mcg
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 4 (100.00%)	3 / 3 (100.00%)	5 / 5 (100.00%)	3 / 3 (100.00%)	5 / 5 (100.00%)	4 / 4 (100.00%)	5 / 5 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	0	0	0	1
Tumour pain
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	1	0	0	0	2	0	1
Vascular disorders
Hypotension
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	3 / 5 (60.00%)
occurrences all number	0	1	0	0	5	1	9
Hypertension
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	1	0	0	1	0	0	2
Hot flush
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	2 / 5 (40.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	2	0	0
Phlebitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Superior vena cava syndrome
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0	0	0	0
General disorders and administration site conditions
Axillary pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Chest discomfort
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Chills
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	3 / 5 (60.00%)	2 / 3 (66.67%)	2 / 5 (40.00%)	3 / 4 (75.00%)	3 / 5 (60.00%)
occurrences all number	0	1	5	7	9	10	14
Face oedema
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Facial pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Fatigue
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 4 (50.00%)	2 / 3 (66.67%)	2 / 5 (40.00%)	2 / 3 (66.67%)	0 / 5 (0.00%)	2 / 4 (50.00%)	3 / 5 (60.00%)
occurrences all number	4	3	2	4	0	4	4
Feeling cold
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Influenza like illness
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Local swelling
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	2	0	0	0
Malaise
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	0	0	0	1
Non-cardiac chest pain
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	2	0	1	0	0	0	0
Oedema peripheral
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)
occurrences all number	1	0	0	0	0	1	1
Pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	2	0	0	0	0	0
Pyrexia
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 4 (50.00%)	2 / 3 (66.67%)	4 / 5 (80.00%)	3 / 3 (100.00%)	5 / 5 (100.00%)	3 / 4 (75.00%)	5 / 5 (100.00%)
occurrences all number	5	3	11	7	10	8	16
Immune system disorders
Cytokine release syndrome
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	2 / 3 (66.67%)	2 / 5 (40.00%)	3 / 4 (75.00%)	5 / 5 (100.00%)
occurrences all number	0	0	0	2	4	6	14
Reproductive system and breast disorders
Amenorrhoea
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Menstruation irregular
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Pelvic pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Vaginal haemorrhage
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Oropharyngeal pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	1	1	0	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	2 / 3 (66.67%)	1 / 5 (20.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	0 / 4 (0.00%)	3 / 5 (60.00%)
occurrences all number	2	2	1	2	1	0	5
Cough
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 4 (50.00%)	1 / 3 (33.33%)	2 / 5 (40.00%)	2 / 3 (66.67%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	2	1	2	4	0	0	0
Hypoxia
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	1 / 4 (25.00%)	2 / 5 (40.00%)
occurrences all number	1	0	0	2	0	2	4
Epistaxis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	3	1	0	0	0
Nasal congestion
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	1	0	0	0	1
Pleural effusion
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	1	0	0	0	0	0	1
Dry throat
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Dysphonia
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Pulmonary haemorrhage
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Upper respiratory tract irritation
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Psychiatric disorders
Anxiety
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	2 / 5 (40.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	2	0	0
Confusional state
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	3	0	0	0
Insomnia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Product issues
Thrombosis in device
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Investigations
Alanine aminotransferase increased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	2	0	0
Amylase increased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Aspartate aminotransferase increased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	1	0	2	0	6
Blood bilirubin increased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Blood creatinine increased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Blood lactate dehydrogenase increased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Body temperature increased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	2	0	0	0
Breath sounds abnormal
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Heart rate increased
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Lymphocyte count decreased
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	2 / 3 (66.67%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	2	0	1	0
Neutrophil count decreased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	2 / 4 (50.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	0	0	5	1
Oxygen saturation decreased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1	0	0	1
Weight decreased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)
occurrences all number	0	3	0	0	0	1	1
Weight increased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
White blood cell count decreased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	0	2	0
Injury, poisoning and procedural complications
Contusion
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	1	0	0	0	1
Hand fracture
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	2	0	0	0	0	0
Infusion related reaction
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Cardiac disorders
Sinus tachycardia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	1	0	0	0	0	4
Tachycardia
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Nervous system disorders
Headache
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 4 (50.00%)	3 / 3 (100.00%)	4 / 5 (80.00%)	3 / 3 (100.00%)	2 / 5 (40.00%)	1 / 4 (25.00%)	4 / 5 (80.00%)
occurrences all number	3	6	8	7	4	1	5
Dysgeusia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	1	0	0	0	0
Tremor
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	1	0	0	0	0	1
Dizziness
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Neuralgia
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Paraesthesia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Phantom pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Somnolence
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Blood and lymphatic system disorders
Anaemia
alternative assessment type: Non-systematic
subjects affected / exposed	4 / 4 (100.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)
occurrences all number	7	6	8	0	0	0	8
Neutropenia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	1	0	1	0	1
Ear and labyrinth disorders
Ear discomfort
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Vertigo
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	1	0	0
Eye disorders
Dry eye
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Eye pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Eyelid oedema
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal pain
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)
occurrences all number	1	0	1	0	2	1	0
Constipation
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	1 / 3 (33.33%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)
occurrences all number	1	2	2	0	0	1	2
Diarrhoea
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	1	1	0	3	0	0
Duodenal ulcer
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Gastritis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Mouth haemorrhage
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	0	0	0	1
Mouth ulceration
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Nausea
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 4 (50.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	1 / 3 (33.33%)	3 / 5 (60.00%)	2 / 4 (50.00%)	1 / 5 (20.00%)
occurrences all number	2	2	0	1	4	2	4
Stomatitis
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	1	0	0	0	0
Vomiting
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	2 / 3 (66.67%)	2 / 5 (40.00%)	2 / 3 (66.67%)	1 / 5 (20.00%)	2 / 4 (50.00%)	2 / 5 (40.00%)
occurrences all number	0	6	4	2	2	2	4
Hepatobiliary disorders
Hepatic failure
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Skin and subcutaneous tissue disorders
Dry skin
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	1	1	0	0
Pruritus generalised
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	1	0	0
Alopecia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Erythema
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Night sweats
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Purpura
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Rash erythematous
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Rash maculo-papular
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Skin mass
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Endocrine disorders
Adrenal insufficiency
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	10	0	0	0	0	0
Hypothyroidism
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	3	1	0
Back pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	4	2	0	0	0	0
Bone pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Flank pain
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	0	0	0	1
Muscle rigidity
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Muscle tightness
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Muscular weakness
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Musculoskeletal chest pain
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	2	0	0	0	0	0	1
Myalgia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	2 / 3 (66.67%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	2	1	0	0
Pain in extremity
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)
occurrences all number	0	2	1	0	0	1	0
Infections and infestations
Coronavirus infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	0	0	0	1
Localised infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Oral candidiasis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	1	0	0	0
Pharyngitis
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	2	0	0	0	0	0	0
Rhinitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0
Sinusitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	1	0	0	0	0	0
Skin infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Viral respiratory tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	1	0	0	0
Urinary tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	1	0	0
Metabolism and nutrition disorders
Decreased appetite
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)
occurrences all number	0	1	1	0	0	0	3
Dehydration
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	0	1	0
Hypercalcaemia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	1	0	0	0
Hypokalaemia
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)
occurrences all number	5	0	0	0	0	0	0
Hypophosphataemia
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)
occurrences all number	3	0	0	0	1	2	0

More information

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Were there any global substantial amendments to the protocol? Yes

15 Jan 2018

--Additional DLT criterion added --Updated inclusion criteria #10 to require that during Phase II patients with NSCLC harboring anaplastic lymphoma kinase rearrangements or EGFR mutations have had prior treatment with Health --Authority-approved targeted therapies --Duration of sample storage was added --Additional emergency contact added on cover page --Corrected typographical errors and inconsistencies and inserted minor clarifications throughout to improve the readability and content presentation

12 Jun 2019

--Description of potential risks was revised to incorporate emerging data from related molecules including the ImmTAC IMCgp100. The CRS section was updated to include frequencies of relevant AEs. -----Potential risks of hepatic and pulmonary events were added. --Added provision to allow enrollment in expansion cohorts to be increased from n=9 to n=24 (previously fixed at n=10) --Response was no longer to be evaluated per modified irRECIST. Treatment discontinuation was required when unequivocal disease progression was confirmed, aligned with current standards. Intrapatient dose-escalation approaches were modified based on beneficial data in other CD3 bispecifics to allow the SST to initiate a 1-step or 2-step IPE regimen and/or allow pre-medication. A longer DLT evaluation period and adjusted Cycle 1 schedule were added for patients who were receiving IPE. --The first 3 patients at each dose level were to be hospitalized for 2 nights after the first dose of IMCnyeso. --DLT criteria were revised --Allowed/prohibited concomitant medications were edited --Toxicity management guidelines were updated to align with protocols for other ImmTAC molecules. --The schedule of assessment tables were reformatted for ease of use with a few clarifications --Safety follow-up was changed to 30 days, based on the <24-hour half-life of ImmTAC.

24 Feb 2020

--To reduce the risk to patients from acute mechanism-related toxicities by moving to IPE regimens, the dose-escalation rules were updated, so that at any escalation step, a new permitted dose level based on the BLRM could be assessed using the same regimen as the prior cohort or using a regimen with additional steps. Furthermore, because ImmTAC-associated toxicities are generally acute, a 28-day DLT period was be used for all schedules. --Based on the observation that all signs/symptoms of CRS, to date, had occurred rapidly (within a few hours) following administration of IMCnyeso, the SST could decide to reduce the minimum required post-end of infusion monitoring time to no less than 8 hours on C1D1, C1D8, and/or C1D15 during the Phase II portion of the study. Consistent with prior versions of the protocol, hospitalization would be extended if clinically indicated for any given patient. --Eligibility criteria were updated based on investigator feedback as follows: a. Patients with a clinically stable, asymptomatic Grade 2 endocrine disorder due to prior anti-cancer therapy (previously restricted to hypothyroidism) were permitted to be enrolled in the study. b. The minimum allowed creatinine clearance (calculated using Cockcroft-Gault formula or measured) was reduced from 50 mL/min to 40 mL/min. c. The washout period for oral antibiotics was reduced from 14 days to 7 days prior to the first dose of study drug (note: no change was made to the washout period for IV antibiotics). 4. Instructions for allowed and prohibited concomitant medications were edited to include guidance regarding vaccine use. --If dose escalation proceeded to a dose of >150 mcg according to BLRM output and treatment at this dose level is well tolerated, additional BLRM simulations were to be performed to predict rates of toxicity for higher dose levels.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
10 May 2021	Following portfolio review, the study was terminated early (prior to initiation of Phase 2) by the Sponsor as a strategic decision (not based on any safety signal).	-

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

None reported

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Secondary: Number of Subjects With Anti-IMCnyeso Antibody Formation

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