Download PDF

Clinical Trial Results:
Clinical and Immunologic Activity of Nemvaleukin Alfa With a Less Frequent IV Dosing Schedule as Monotherapy and in Combination With Pembrolizumab and Impact on Tumor Microenvironment in Solid Tumor Patients (ARTISTRY-3)

Summary
EudraCT number	2022-003662-21
Trial protocol	ES
Global end of trial date	11 Jun 2024

Results information
Results version number	v1(current)
This version publication date	17 Jul 2025
First version publication date	17 Jul 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

ALKS4230-003

ISRCTN number

US NCT number

NCT04592653

WHO universal trial number (UTN)

Sponsor organisation name

Alkermes, Inc.

Sponsor organisation address

852 Winter Street, Waltham, United States, 02451-1420

Public contact

Richard Campbell, Alkermes, Inc., +1 781786-1058, richard.campbell@muraloncology.com

Scientific contact

Richard Campbell, Alkermes, Inc., +1 781786-1058, richard.campbell@muraloncology.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

11 Jun 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

11 Jun 2024

Was the trial ended prematurely?

Main objective of the trial

Cohort 1 (TME): • To evaluate the effects of nemvaleukin alfa (‘nemvaleukin,’ ‘ALKS 4230’) monotherapy on the TME of a variety of advanced, malignant solid tumors. Cohort 2 (Less Frequent IV Dosing): • To investigate the safety and tolerability of less frequent IV dosing schedules of nemvaleukin to identify and determine a recommended phase 2 dose (RP2D) of nemvaleukin monotherapy. • To determine the maximum tolerated dose (MTD) of nemvaleukin monotherapy and in combination with pembrolizumab.

Protection of trial subjects

This study was conducted in accordance with the protocol, the ICH Guideline E6, and all applicable local regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Sep 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 44

Country: Number of subjects enrolled

Spain: 17

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

Top of page

Recruitment details

The study was conducted at 6 investigative sites in Spain and the United States. This study was conducted in two cohorts: Cohort 1 (Tumor Microenvironment [TME]) and Cohort 2 (Less Frequent Dosing). Cohort 2 consisted of Part A (monotherapy with nemvaleukin) and Part B (combination therapy with nemvaleukin and pembrolizumab).

Screening details

As pre-specified in statistical analysis plan (SAP), Part B of Cohort 2 was not conducted and no subject was enrolled, therefore, no data was collected and reported for Cohort 2 Part B.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg

Arm description

Subjects received nemvaleukin alfa 6 micrograms per kilogram (mcg/kg), intravenous (IV) infusion, once daily for 5 consecutive days, followed by 9 days off during Cycle 1 (Cycle 1 length=14 days) and 16 days off during Cycle 2 (Cycle 2 length=21 days), then a single dose on Day 1 of each 21-day cycle in combination with pembrolizumab 200 milligrams (mg), IV infusion until subjects deriving clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Investigational medicinal product name

Pembrolizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Pembrolizumab administered as IV infusion.

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg

Arm description

Subjects received nemvaleukin alfa 10 mcg/kg, IV infusion, once on Day 1 of each 21-day cycle until subject derived clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg

Arm description

Subjects received nemvaleukin alfa 20 mcg/kg, IV infusion, once on Day 1 of each 21-day cycle until subjects deriving clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg

Arm description

Subjects received nemvaleukin alfa 30 mcg/kg, IV infusion, once on Day 1 of each 21-day cycle until subject deriving clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg

Arm description

Subjects received nemvaleukin alfa 35 mcg/kg, IV infusion, once on Day 1 of each 21-day cycle until subject deriving clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg

Arm description

Subjects received nemvaleukin alfa 40 mcg/kg, IV infusion, once on Day 1 of each 21-day cycle until subjects deriving clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg

Arm description

Subjects received nemvaleukin alfa 20 mcg/kg, IV infusion, once on Days 1 and 8 of each 21-day cycle until subjects derived clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg

Arm description

Subjects received nemvaleukin alfa 25 mcg/kg, IV infusion, once on Days 1 and 8 of each 21-day cycle until subjects derived clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg

Arm description

Subjects received nemvaleukin alfa 30 mcg/kg, IV infusion, once on Days 1 and 8 of each 21-day cycle until subjects derived clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg

Arm description

Subjects received nemvaleukin alfa 15 mcg/kg, IV infusion, once on Days 1 and 4 of each 21-day cycle until subjects derived clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg

Arm description

Subjects received nemvaleukin alfa 20 mcg/kg, IV infusion, once on Days 1 and 4 of each 21-day cycle until subjects derived clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg

Arm description

Subjects received nemvaleukin alfa 25 mcg/kg, IV infusion, once on Days 1 and 4 of each 21-day cycle until subjects derived clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg

Arm description

Subjects received nemvaleukin alfa 30 mcg/kg, IV infusion, once on Days 1 and 4 of each 21-day cycle until subjects derived clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg

Arm description

Subjects received nemvaleukin alfa 35 mcg/kg, IV infusion, once on Days 1 and 4 of each 21-day cycle until subjects derived clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Arm type

Experimental

Investigational medicinal product name

Nemvaleukin Alfa

Investigational medicinal product code

Other name

ALKS 4230

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nemvaleukin alfa administered as IV infusion.

Number of subjects in period 1	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Started	9	1	1	5	6	4	5	5	3	3	3	6	3	7
Completed	0	0	0	1	0	2	0	0	2	1	0	0	1	2
Not completed	9	1	1	4	6	2	5	5	1	2	3	6	2	5
Consent withdrawn by subject	7	-	1	1	-	-	1	1	-	1	-	2	1	1
Death	1	1	-	3	6	2	3	4	1	-	3	1	-	4
Lost to follow-up	1	-	-	-	-	-	1	-	-	1	-	3	1	-

Baseline characteristics

Top of page

Reporting group title

Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg

Reporting group description

Reporting group values	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg	Total
Number of subjects	9	1	1	5	6	4	5	5	3	3	3	6	3	7	61
Age categorical
Units: Subjects
<=18 years	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Between 18 and 65 years	6	1	1	3	1	2	3	2	3	3	1	5	2	5	38
>=65 years	3	0	0	2	5	2	2	3	0	0	2	1	1	2	23
Gender categorical
Units: Subjects
Female	8	0	1	3	5	2	2	5	3	3	2	3	2	6	45
Male	1	1	0	2	1	2	3	0	0	0	1	3	1	1	16
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	0	0	0	0	0	2	0	0	0	0	0	0	0	2
Not Hispanic or Latino	9	1	1	5	6	4	3	5	3	3	3	6	3	7	59
Race (NIH/OMB)
Units: Subjects
Asian	0	0	0	0	0	0	1	0	0	0	1	1	0	0	3
Black or African American	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
White	9	1	1	5	6	4	2	5	3	3	1	5	3	7	55
Unknown or Not Reported	0	0	0	0	0	0	2	0	0	0	0	0	0	0	2

End points

Top of page

Reporting group title

Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg

Reporting group description

Subject analysis set title

Cohort 1, Monotherapy: Nemvaleukin Alfa 6 mcg/kg

Subject analysis set type

Safety analysis

Subject analysis set description

The safety population included all subjects who received any exposure to nemvaleukin alfa.

Primary: Cohort 1: Change From Baseline in Density of Immune Cells: Total T Cells, Cluster of Differentiation (CD)8+ T Cells, CD56+ Cells, and Regulatory T Cells (Tregs) at Cycle 2 Day 8 in Paired Tumor Biopsies

Top of page

End point title

Cohort 1: Change From Baseline in Density of Immune Cells: Total T Cells, Cluster of Differentiation (CD)8+ T Cells, CD56+ Cells, and Regulatory T Cells (Tregs) at Cycle 2 Day 8 in Paired Tumor Biopsies ^[1]

End point description

The biopsies samples were collected and analyzed by immunohistochemistry (IHC) and/or immunofluorescence (IF). TME-evaluable population included subjects who had a confirmed diagnosis of one of included tumor types; had received specified minimum 4 out of 5 doses of nemvaleukin alfa (6 mcg/kg/day) during each of the first 2 cycles and completed doses of assigned less frequent IV dosing recommended phase 2 dose (RP2D) in the first 2 cycles; had contributed paired biopsies; and had not received any confounding therapies before the second biopsy (Cycle 2).

End point type

Primary

End point timeframe

Baseline, at Cycle 2 Day 8 (Cycle 2 length=21 days)

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: Only descriptive data was planned.

End point values	Cohort 1, Monotherapy: Nemvaleukin Alfa 6 mcg/kg
Number of subjects analysed	8
Units: cell counts per millimeter square
arithmetic mean (standard deviation)
Total T Cells: Total Region of Interest (ROI)	108.5 ( 474.87 )
Total T Cells: Within Tumor	-11.4 ( 158.27 )
Total T Cells: Outside Tumor	113.4 ( 630.59 )
CD8+: Total ROI	-72.6 ( 209.82 )
CD8+: Within Tumor	-39.3 ( 78.65 )
CD8+: Outside Tumor	-84.4 ( 258.03 )
CD56+: Total ROI	-196.1 ( 568.90 )
CD56+: Within Tumor	-221.4 ( 696.71 )
CD56+: Outside Tumor	-97.0 ( 332.26 )
Treg: Total ROI	7.2 ( 57.16 )
Treg: Within Tumor	-1.0 ( 10.44 )
Treg: Outside Tumor	9.2 ( 67.46 )

No statistical analyses for this end point

Primary: Cohort 1: Change From Baseline in Ratio of T/Treg, CD8+/Treg, CD56+/Tregs at Cycle 2 Day 8 in Paired Tumor Biopsies

Top of page

End point title

Cohort 1: Change From Baseline in Ratio of T/Treg, CD8+/Treg, CD56+/Tregs at Cycle 2 Day 8 in Paired Tumor Biopsies ^[2]

End point description

The biopsies samples were collected and analyzed by immunohistochemist. TME-evaluable population included subjects who had a confirmed diagnosis of one of included tumor types; had received specified minimum 4 out of 5 doses of nemvaleukin (6 mcg/kg/day) during each of the first 2 cycles and completed doses of assigned less frequent IV dosing RP2D in the first 2 cycles; had contributed paired biopsies; and had not received any confounding therapies before the second biopsy (Cycle 2).

End point type

Primary

End point timeframe

Baseline, at Cycle 2 Day 8 (Cycle 2 length=21 days)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned.

End point values	Cohort 1, Monotherapy: Nemvaleukin Alfa 6 mcg/kg
Number of subjects analysed	8
Units: ratio
arithmetic mean (standard deviation)
T/Treg: Total ROI	11.1 ( 57.05 )
T/Treg: Within Tumor	53.8 ( 144.88 )
T/Treg: Outside Tumor	3.3 ( 45.73 )
CD8+/Treg: Total ROI	-1.0 ( 4.21 )
CD8+/Treg: Within Tumor	-2.1 ( 5.00 )
CD8+/Treg: Outside Tumor	-1.0 ( 4.48 )
CD56+/Treg: Total ROI	4.6 ( 43.69 )
CD56+/Treg: Within Tumor	-212.9 ( 1096.11 )
CD56+/Treg: Outside Tumor	-20.3 ( 87.39 )

No statistical analyses for this end point

Primary: Cohort 2 (Less Frequent IV Dosing): Number of Participants With of Dose-limiting Toxicity (DLT)

Top of page

End point title

Cohort 2 (Less Frequent IV Dosing): Number of Participants With of Dose-limiting Toxicity (DLT) ^[3] ^[4]

End point description

DLTs was defined by any of the following events with some exceptions that were observed during the interval from Cycle 1 Day 1 through Cycle 1 Day 21 and were deemed as possibly, probably, or definitely related to nemvaleukin alfa: Hematologic: Grade 4 neutropenia or thrombocytopenia lasting greater than (>) 7 days and Grade 3 thrombocytopenia with bleeding requiring transfusion or medical intervention; Non-hematologic: Any Grade greater than or equal to (>=) 3 nonhematologic adverse events (AEs) that did not resolve to Grade 2 or lower within 7 days. The DLT-evaluable population included subjects who had a confirmed diagnosis of one of the included tumor types, had received the specified dose of nemvaleukin during the first cycle as per schedule assigned and had completed 21-day follow-up in Cycle 1.

End point type

Primary

End point timeframe

Cycle 1 Day 1 through Cycle 1 Day 21 (Cycle 1 length =14 days)

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: Only descriptive data was planned.
[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: Only descriptive data was planned.

End point values	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	1	1	5	6	4	4	4	3	3	3	4	3	5
Units: participants	0	0	0	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Overall Response Rate (ORR) Based on RECIST 1.1

Top of page

End point title

Overall Response Rate (ORR) Based on RECIST 1.1

End point description

ORR was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) based on Investigator review of the radiographic or photographic images, as defined according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR: At least a 30 percentage (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The safety population included all subjects who received any exposure to nemvaleukin alfa.

End point type

Secondary

End point timeframe

From time of initiation of therapy until the date of first documented tumor progression (up to 12 weeks for Cohort 1; up to 39 weeks for Cohort 2)

Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg

Number of subjects analysed

Units: percentage of participants

number (confidence interval 95%)

0.0 (0.0 to 33.6)

0.0 (0.0 to 97.5)

0.0 (0.0 to 52.2)

0.0 (0.0 to 45.9)

0.00 (0.0 to 60.2)

0.00 (0.00 to 52.2)

0.00 (0.00 to 70.8)

0.00 (0.00 to 45.9)

0.00 (0.00 to 70.8)

0.00 (0.00 to 41.0)

No statistical analyses for this end point

Secondary: Overall Response Rate (ORR) Based on iRECIST

Top of page

End point title

Overall Response Rate (ORR) Based on iRECIST

End point description

ORR was defined as the percentage of participants with confirmed immune complete response (iCR) or immune partial response (iPR) based on Investigator review of the radiographic or photographic images, as defined according to immune Response Evaluation Criteria in Solid Tumors (iRECIST) v1.1. iCR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be <10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. The safety population included all subjects who received any exposure to nemvaleukin alfa.

End point type

Secondary

End point timeframe

From time of initiation of therapy until the date of first documented tumor progression (up to 12 weeks for Cohort 1; up to 39 weeks for Cohort 2)

Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg

Number of subjects analysed

Units: percentage of participants

number (confidence interval 95%)

0.0 (0.0 to 33.6)

0.0 (0.0 to 97.5)

0.0 (0.0 to 52.2)

0.0 (0.0 to 45.9)

0.00 (0.00 to 60.2)

0.00 (0.00 to 52.2)

0.00 (0.00 to 70.8)

0.00 (0.00 to 45.9)

0.00 (0.00 to 70.8)

0.00 (0.00 to 41.0)

No statistical analyses for this end point

Secondary: Duration of Response (DOR) Among Confirmed Responders Based on RECIST 1.1

Top of page

End point title

Duration of Response (DOR) Among Confirmed Responders Based on RECIST 1.1

End point description

The DOR was defined as the time from the first documentation of response (PR or CR) to the first documentation of objective tumor progression or death due to any cause based on RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The safety population included all subjects who received any exposure to nemvaleukin alfa. Here, "Overall Number of Participants Analyzed" signifies participants who had confirmed response (CR or PR).

End point type

Secondary

End point timeframe

From the first documentation of response (PR or CR) to the first documentation of objective tumor progression or death due to any cause (up to 12 weeks for Cohort 1; up to 39 weeks for Cohort 2)

Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg

Number of subjects analysed

0 ^[5]

0 ^[6]

0 ^[7]

0 ^[8]

0 ^[9]

0 ^[10]

0 ^[11]

0 ^[12]

0 ^[13]

0 ^[14]

0 ^[15]

0 ^[16]

0 ^[17]

0 ^[18]

Units: months

median (full range (min-max))

( to )

Notes
[5] - Endpoint has zero total participants analyzed.
[6] - Endpoint has zero total participants analyzed.
[7] - Endpoint has zero total participants analyzed.
[8] - Endpoint has zero total participants analyzed.
[9] - Endpoint has zero total participants analyzed.
[10] - Endpoint has zero total participants analyzed.
[11] - Endpoint has zero total participants analyzed.
[12] - Endpoint has zero total participants analyzed.
[13] - Endpoint has zero total participants analyzed.
[14] - Endpoint has zero total participants analyzed.
[15] - Endpoint has zero total participants analyzed.
[16] - Endpoint has zero total participants analyzed.
[17] - Endpoint has zero total participants analyzed.
[18] - Endpoint has zero total participants analyzed.

No statistical analyses for this end point

Secondary: Duration of Response (DOR) Among Confirmed Responders Based on iRECIST 1.1

Top of page

End point title

Duration of Response (DOR) Among Confirmed Responders Based on iRECIST 1.1

End point description

The DOR was defined as the time from the first documentation of response (iPR or iCR) to the first documentation of objective tumor progression or death due to any cause based on iRECIST 1.1. iCR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be <10 mm in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. The safety population included all subjects who received any exposure to nemvaleukin alfa. Here, "Overall Number of Participants Analyzed" signifies participants who had confirmed response (CR or PR).

End point type

Secondary

End point timeframe

From the first documentation of response (iPR or iCR) to the first documentation of objective tumor progression or death due to any cause (up to 12 weeks for Cohort 1; up to 39 weeks for Cohort 2)

Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg

Number of subjects analysed

0 ^[19]

0 ^[20]

0 ^[21]

0 ^[22]

0 ^[23]

0 ^[24]

0 ^[25]

0 ^[26]

0 ^[27]

0 ^[28]

0 ^[29]

0 ^[30]

0 ^[31]

0 ^[32]

Units: months

median (full range (min-max))

( to )

Notes
[19] - Data collection or analysis based on iRECIST was not performed.
[20] - Data collection or analysis based on iRECIST was not performed.
[21] - Data collection or analysis based on iRECIST was not performed.
[22] - Data collection or analysis based on iRECIST was not performed.
[23] - Data collection or analysis based on iRECIST was not performed.
[24] - Data collection or analysis based on iRECIST was not performed.
[25] - Data collection or analysis based on iRECIST was not performed.
[26] - Data collection or analysis based on iRECIST was not performed.
[27] - Data collection or analysis based on iRECIST was not performed.
[28] - Data collection or analysis based on iRECIST was not performed.
[29] - Data collection or analysis based on iRECIST was not performed.
[30] - Data collection or analysis based on iRECIST was not performed.
[31] - Data collection or analysis based on iRECIST was not performed.
[32] - Data collection or analysis based on iRECIST was not performed.

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and TEAEs Severity Grade 3 or Higher

Top of page

End point title

Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and TEAEs Severity Grade 3 or Higher

End point description

TEAEs were defined as AEs that occur or worsen after the first dose of study drug(s). An AE was any untoward medical occurrence in a subject or clinical investigation subject who had been administered a pharmaceutical product. Severity was evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, where Grade 3: Severe or medically significant but not immediately life-threatening: hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL). Grade 4: Life-threatening consequences: urgent intervention indicated. Grade 5: Death related to AE. The safety population included all subjects who received any exposure to nemvaleukin alfa

End point type

Secondary

End point timeframe

From first dose of study drug up to 30 days after last dose (up to 16 weeks for Cohort 1; up to 43 weeks for Cohort 2)

End point values	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg	Cohort 1, Monotherapy: Nemvaleukin Alfa 6 mcg/kg
Number of subjects analysed	4	1	1	5	6	4	5	5	3	3	3	6	3	7	9
Units: participants
TEAEs	4	1	1	5	6	4	5	5	3	3	3	6	3	7	9
TEAEs Severity Grade 3 or Higher	2	1	1	3	2	2	2	3	2	1	2	4	2	3	8

No statistical analyses for this end point

Secondary: Number of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs Values

Top of page

End point title

Number of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs Values

End point description

Potentially clinically significant criteria in vital sign were defined as systolic blood pressure (SBP) >=160 or diastolic blood pressure (DBP) >=100, or SBP less than or equal to (<=) 90 or DBP <=60, or Temperature >40 degree centigrade (℃). The safety population included all subjects who received any exposure to nemvaleukin alfa

End point type

Secondary

End point timeframe

From first dose of study drug up to 30 days after last dose (up to 16 weeks for Cohort 1; up to 43 weeks for Cohort 2)

End point values	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	9	1	1	5	6	4	5	5	3	3	3	6	3	7
Units: participants
SBP >=160	2	0	0	0	0	0	0	3	2	0	0	0	0	1
DBP >=100	1	0	0	0	0	0	0	1	0	0	0	0	0	0
SBP <=90	7	0	0	0	3	2	2	1	2	1	1	4	3	3
DBP <=60	0	0	1	3	4	3	4	4	3	3	3	4	3	5
Temperature >40℃	0	0	0	0	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants With Clinically Significant Abnormal Changes From Baseline in Laboratory Tests

Top of page

End point title

Number of Participants With Clinically Significant Abnormal Changes From Baseline in Laboratory Tests

End point description

Laboratory tests hematology, serum chemistry, and urinalysis assessment. Any clinically significant abnormality was based on Investigator's assessment. The safety population included all subjects who received any exposure to nemvaleukin alfa.

End point type

Secondary

End point timeframe

Laboratory tests hematology, serum chemistry, and urinalysis assessment. Any clinically significant abnormality was based on Investigator's assessment.

End point values	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	9	1	1	5	6	4	5	5	3	3	3	6	3	7
Units: participants	0	0	0	0	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants With Clinically Significant Change From Baseline in Electrocardiograms (ECGs) Values

Top of page

End point title

Number of Participants With Clinically Significant Change From Baseline in Electrocardiograms (ECGs) Values

End point description

Any clinically significant abnormality was based on Investigator's assessment. The safety population included all subjects who received any exposure to nemvaleukin alfa.

End point type

Secondary

End point timeframe

From first dose of study drug up to 30 days after last dose (up to 16 weeks for Cohort 1; up to 43 weeks for Cohort 2)

End point values	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	9	1	1	5	6	4	5	5	3	3	3	6	3	7
Units: participants	0	0	0	0	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Cohort 1: Concentrations of Nemvaleukin in Serum

Top of page

End point title

Cohort 1: Concentrations of Nemvaleukin in Serum ^[33]

End point description

The pharmacokinetic (PK) population included subjects who received at least 1 dose of nemvaleukin and have at least 1 measurable serum concentration of nemvaleukin at any scheduled PK time point. Here, "Number Analyzed" signifies subjects evaluable at given timepoints. "99999" means data could not be estimated due to insufficient events.

End point type

Secondary

End point timeframe

At pre-dose and within 5 minutes of End of Infusion (EOI) on Days 1 and 5 of Cycles 1 and 2; At pre-dose and within 5 minutes of EOI on Day 1 of Cycles 3 and 4 (Cycle 1 length = 14 days; Cycle 2, 3 and 4 length= 21 days)

Notes
[33] - 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: Only descriptive data was planned.

End point values	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Number of subjects analysed	9
Units: nanograms per milliliter (ng/mL)
arithmetic mean (standard deviation)
Cycle 1 Day 1: Predose (n=9)	0 ( 99999 )
Cycle 1 Day 1: Within 5 minutes of EOI (n=9)	114.1 ( 62.47 )
Cycle 1 Day 5: Predose (n=8)	3.0 ( 1.50 )
Cycle 1 Day 5: Within 5 minutes of EOI (n=8)	125.4 ( 41.39 )
Cycle 2 Day 1: Predose (n=9)	0 ( 99999 )
Cycle 2 Day 1: Within 5 minutes of EOI (n=9)	120.3 ( 14.44 )
Cycle 2 Day 5: Predose (n=9)	2.7 ( 1.31 )
Cycle 2 Day 5: Within 5 minutes of EOI (n=9)	105.0 ( 26.67 )
Cycle 3 Day 1: Predose (n=4)	0 ( 99999 )
Cycle 3 Day 1: Within 5 minutes of EOI (n=4)	83.6 ( 33.54 )
Cycle 4 Day 1: Predose (n=2)	0 ( 99999 )
Cycle 4 Day 1: Within 5 minutes of EOI (n=2)	90.2 ( 22.72 )

No statistical analyses for this end point

Secondary: Cohort 2: Concentrations of Nemvaleukin in Serum

Top of page

End point title

Cohort 2: Concentrations of Nemvaleukin in Serum ^[34]

End point description

The PK population included subjects who received at least 1 dose of nemvaleukin alfa and had at least 1 measurable serum concentration of nemvaleukin alfa at any scheduled PK time point. Here, "number of subjects analyzed" signifies subjects who were evaluable for this endpoint and "n" signifies subjects who were evaluable at specified timepoints. Here, "99999" means data could not be calculated due to less subject and "9999” means data could not be evaluated as no subject was evaluated.

End point type

Secondary

End point timeframe

Cycle 1 and 2 Day 1: Pre-dose, 1, 2, 4, 8 hours post-dose and within 5 minutes from the EOI; Cycle 1 and 2 Day 4; Cycle 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 13: Pre-dose and within 5 minutes from the EOI (Cycle 1 = 14 days; other Cycles = 21 days)

Notes
[34] - 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: Only descriptive data was planned.

End point values	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	1	1	5	6	4	5	5	3	3	3	6	3	7
Units: ng/mL
arithmetic mean (standard deviation)
C1 D1: Predose (n=1,1,5,6,4,5,5,3,3,3,6,3, 7)	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	3 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )
C1 D1:1 Hr Post Inf (n=1,1,5,6,4,5,5,3,3,3,6,3,7)	81.7 ( 99999 )	512.7 ( 99999 )	536.5 ( 149.89 )	511.2 ( 248.50 )	749.9 ( 327.76 )	271.0 ( 94.88 )	345.1 ( 63.24 )	467.0 ( 27.70 )	375.9 ( 15.55 )	475.3 ( 292.23 )	392.0 ( 117.51 )	407.4 ( 40.52 )	590.9 ( 128.85 )
C1 D1:2 Hr Post Inf (n=1,1,5,6,4,4,5,3,3,3,6,3,7)	161.6 ( 99999 )	413.6 ( 99999 )	723.0 ( 669.04 )	568.3 ( 525.29 )	885.7 ( 570.36 )	249.1 ( 126.02 )	283.3 ( 34.21 )	308.5 ( 87.35 )	321.2 ( 123.50 )	329.6 ( 136.55 )	313.5 ( 74.34 )	339.6 ( 65.43 )	502.6 ( 141.64 )
C1 D1:4 Hr Post Inf (n=1,1,5,6,4,4,5,3,3,3,6,3,7)	92.5 ( 9999 )	103.3 ( 99999 )	456.5 ( 301.13 )	269.5 ( 143.16 )	423.6 ( 220.23 )	140.5 ( 59.78 )	190.1 ( 44.29 )	229.4 ( 6.81 )	142.6 ( 154.06 )	227.0 ( 102.52 )	231.8 ( 70.63 )	226.3 ( 34.19 )	287.3 ( 88.88 )
C1 D1:8 Hr Post Inf (n=1,1,3,6,4,4,5,3,3,3,6,3,7)	33.2 ( 9999 )	110.5 ( 99999 )	226.4 ( 146.60 )	108.8 ( 62.05 )	309.9 ( 130.26 )	78.9 ( 30.91 )	97.1 ( 16.04 )	116.7 ( 54.26 )	118.9 ( 92.98 )	120.8 ( 75.18 )	108.3 ( 21.65 )	80.1 ( 34.07 )	208.5 ( 96.99 )
C1D1: In 5m from EOI(n=1,1,4,6,4,5,5,3,3,3,6,3,7)	174.7 ( 9999 )	546.7 ( 99999 )	906.3 ( 662.31 )	662.0 ( 442.53 )	999.4 ( 543.38 )	338.3 ( 129.85 )	412.3 ( 66.88 )	436.1 ( 140.65 )	427.8 ( 30.36 )	456.1 ( 178.76 )	401.2 ( 76.75 )	461.4 ( 76.94 )	670.9 ( 186.47 )
C1 D4 (n=1,1,5,5,4,5,5,3,0,0,0,0,0)	9999 ( 99999 )	0 ( 99999 )	2.9 ( 1.62 )	1.9 ( 0.86 )	2.7 ( 0.90 )	1.0 ( 0.71 )	1.2 ( 0.16 )	12.3 ( 18.58 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C2 D1: Predose (n=0,1,3,4,2,4,4,3,3,3,6,3,6)	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	3 ( 99999 )	1 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )
C2 D1: 1 Hr Post Inf (n=0,1,3,4,2,5,4,3,3,3,6,3,6)	9999 ( 9999 )	363.9 ( 99999 )	669.4 ( 314.87 )	583.8 ( 279.09 )	884.2 ( 201.52 )	283.7 ( 83.75 )	332.8 ( 83.19 )	375.6 ( 62.23 )	431.8 ( 162.46 )	407.3 ( 228.72 )	246.5 ( 82.08 )	396.4 ( 66.90 )	575.3 ( 186.18 )
C2 D1: 2 Hr Post Inf (n=0,1,3,4,2,5,5,3,3,3,6,3,6)	9999 ( 9999 )	306.1 ( 99999 )	535.9 ( 101.44 )	497.0 ( 251.06 )	605.0 ( 58.50 )	215.2 ( 81.02 )	235.0 ( 16.58 )	272.1 ( 56.15 )	317.6 ( 75.80 )	383.0 ( 188.02 )	237.9 ( 127.98 )	369.1 ( 60.21 )	479.7 ( 179.55 )
C2 D1: 4 Hr Post Inf (n=0,1,3,4,2,5,4,3,3,3,6,3,6)	9999 ( 9999 )	182.5 ( 99999 )	408.0 ( 154.81 )	306.7 ( 275.77 )	270.6 ( 290.31 )	130.7 ( 52.81 )	128.7 ( 86.16 )	193.4 ( 37.63 )	189.8 ( 32.43 )	238.9 ( 172.54 )	188.0 ( 148.09 )	221.1 ( 52.34 )	308.6 ( 81.55 )
C2 D1: 8 Hr Post Inf (n=0,1,3,4,2,4,4,3,3,3,5,2,6)	9999 ( 9999 )	68.7 ( 99999 )	244.8 ( 20.43 )	213.0 ( 250.36 )	180.4 ( 55.37 )	61.9 ( 17.64 )	82.1 ( 9.47 )	88.1 ( 29.48 )	88.4 ( 18.40 )	120.1 ( 73.13 )	66.1 ( 19.39 )	106.9 ( 2.28 )	161.5 ( 58.04 )
C2D1: In 5m from EOI(n=0,1,3,4,2,5,5,3,3,3,6,3,6)	9999 ( 9999 )	426.4 ( 99999 )	784.4 ( 251.81 )	622.5 ( 241.93 )	929.8 ( 334.10 )	306.1 ( 134.02 )	330.7 ( 18.08 )	476.5 ( 133.60 )	336.0 ( 106.98 )	536.0 ( 391.82 )	306.8 ( 113.96 )	458.3 ( 121.75 )	692.3 ( 209.98 )
C2 D4 (n=0,1,2,4,2,0,0,0,0,0,0,0,0)	9999 ( 9999 )	0.5 ( 99999 )	1.1 ( 0.27 )	1.5 ( 0.79 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C3 D1: Predose (n=0,0,1,1,0,1,2,1,0,1,3,3,4)	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	0.6 ( 99999 )	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )
C3D1:In 5m from EOI(n=0,0,1,1,0,1,2,1,0,1,3,3,4)	9999 ( 9999 )	9999 ( 9999 )	741.5 ( 99999 )	504.2 ( 99999 )	9999 ( 9999 )	282.6 ( 99999 )	331.8 ( 49.78 )	575.1 ( 99999 )	9999 ( 9999 )	769.5 ( 99999 )	404.3 ( 253.19 )	269 ( 99999 )	697.9 ( 187.85 )
C4 D1: Predose (n=0,0,1,1,0,1,2,1,0,0,2,3,3)	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )
C4 D1:In 5m from EOI(n=0,0,1,1,0,1,2,1,0,0,2,3,3)	9999 ( 9999 )	9999 ( 9999 )	898.2 ( 99999 )	1408.0 ( 99999 )	9999 ( 9999 )	275.2 ( 99999 )	297.1 ( 0.05 )	637.2 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	437.1 ( 147.32 )	384.7 ( 62.27 )	781.7 ( 62.17 )
C5 D1: Predose (n=0,0,1,0,0,1,2,0,0,0,1,1,1)	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )
C5D1: In 5m from EOI (n=0,0,1,0,0,1,2,0,0,0,1,1,1)	9999 ( 9999 )	9999 ( 9999 )	574.3 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	340.5 ( 99999 )	365.6 ( 117.78 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	262.1 ( 99999 )	712.3 ( 99999 )	776.4 ( 99999 )
C6 D1: Predose (n=0,0,1,0,0,1,2,0, 0,0,6,3,7)	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	0 ( 99999 )
C6 D1: In 5m from EOI(n=0,0,1,0,0,1,2,0,0,0,1,1,1)	9999 ( 9999 )	9999 ( 9999 )	581.6 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	289.4 ( 99999 )	331.9 ( 157.69 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	257.8 ( 99999 )	358.8 ( 99999 )	757.0 ( 99999 )
C7 D1: Predose (n=0,0,1,0,0,1,2,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	1.2 ( 99999 )	9999 ( 9999 )
C7D1:In 5m from EOI(n=0,0,0,0,0,1,2,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	396.6 ( 99999 )	358.6 ( 35.74 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	334.1 ( 99999 )	9999 ( 9999 )
C8 D1: Predose (n=0,0,1,0,0,1,2,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	0 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	9999 ( 9999 )
C8D1:In 5m from EOI(n=0,0,0,0,0,1,2,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	436.0 ( 99999 )	311.9 ( 103.16 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	431.6 ( 99999 )	9999 ( 9999 )
C9 D1: Predose (n=0,0,0,0,0,0,1,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	571.0 ( 99999 )	9999 ( 9999 )
C9D1:In 5m from EOI(n=0,0,0,0,0,0,1,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	362.8 ( 99999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	9999 ( 9999 )
C10 D1: Predose (n=0,0,0,0,0,0,0,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	9999 ( 9999 )
C10D1:In 5m from EOI(n=0,0,0,0,0,0,0,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	480.1 ( 99999 )	9999 ( 9999 )
C11 D1: Predose (n=0,0,0,0,0,0,0,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	9999 ( 9999 )
C11D1:In 5m from EOI(n=0,0,0,0,0,0,0,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	487.4 ( 99999 )	9999 ( 9999 )
C12 D1: Predose (n=0,0,0,0,0,0,0,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	9999 ( 9999 )
C12D1:In 5m from EOI(n=0,0,0,0,0,0,0,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	602.1 ( 99999 )	9999 ( 9999 )
C13 D1: Predose (n=0,0,0,0,0,0,0,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	0 ( 99999 )	9999 ( 9999 )
C13D1:In 5m from EOI(n=0,0,0,0,0,0,0,0,0,0,0,1,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	488.8 ( 99999 )	9999 ( 9999 )

No statistical analyses for this end point

Secondary: Cohort 2, Cmax: Maximum Observed Serum Concentration of Nemvaleukin Alfa

Top of page

End point title

Cohort 2, Cmax: Maximum Observed Serum Concentration of Nemvaleukin Alfa ^[35]

End point description

Noncompartmental PK analysis was performed. The PK population included subjects who received at least 1 dose of nemvaleukin alfa and had at least 1 measurable serum concentration of nemvaleukin alfa at any scheduled PK time point. Here, "Number of Subjects Analyzed" signifies subjects evaluable for this outcome measure and "n" signifies subjects evaluable at given timepoints. As planned, this PK parameter was assessed in Cohort 2 only. Here, "99999" means data could not be calculated due to less subject and "9999” means data could not be evaluated as no subject was evaluated for the specified endpoint.

End point type

Secondary

End point timeframe

Cycles 1 and 2: Day 1 (Schedules 1, 2 and 3), Day 4 (Schedule 3 only), and Day 8 (Schedule 2 only): Pre-dose, and within 5 minutes, 1, 2, 4, and 8 hours post-dose (each Cycle length=21 days)

Notes
[35] - 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: Only descriptive data was planned.

End point values	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	1	1	5	6	4	5	5	3	3	3	6	3	7
Units: micrograms per liter (mcg/L)
geometric mean (geometric coefficient of variation)
C1D1 (n=1,1,5,6,4,5,5,3,3,3,6,3,7)	175 ( 99999 )	547 ( 99999 )	769 ( 57.7 )	601 ( 61.0 )	925 ( 47.6 )	339 ( 42.0 )	415 ( 15.7 )	490 ( 9.9 )	430 ( 7.9 )	466 ( 51.2 )	408 ( 25.5 )	457 ( 17.1 )	656 ( 27.7 )
C1D4 (n=0,0,0,0,0,0,0,0,3,3,4,3,5)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	304 ( 24.3 )	456 ( 45.5 )	358 ( 25.9 )	400 ( 13.9 )	632 ( 25.3 )
C1D8 (n=0,0,0,0,0,4,4,3,0,0,0,0,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	298 ( 35.0 )	342 ( 14.4 )	558 ( 46.7 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C2D1 (n=0,1,3,4,2,5,4,3,3,5,4,3,6)	9999 ( 9999 )	426 ( 99999 )	760 ( 31.1 )	596 ( 38.0 )	930 ( 32.8 )	316 ( 44.7 )	353 ( 17.5 )	463 ( 31.4 )	446 ( 34.1 )	362 ( 69.4 )	339 ( 46.6 )	492 ( 16.6 )	665 ( 32.5 )
C2D4 (n=0,0,0,0,0,0,0,0,3,4,4,3,5)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	441 ( 57.1 )	309 ( 57.5 )	316 ( 85.1 )	401 ( 18.7 )	652 ( 32.0 )
C2D8 (n=0,0,0,0,0,3,4,2,0,0,0,0,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	307 ( 14.9 )	353 ( 7.3 )	646 ( 30.3 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )

No statistical analyses for this end point

Secondary: Cohort 2, Tmax: Time to Reach Cmax of Nemvaleukin Alfa

Top of page

End point title

Cohort 2, Tmax: Time to Reach Cmax of Nemvaleukin Alfa ^[36]

End point description

End point type

Secondary

End point timeframe

Cycles 1 and 2: Day 1 (Schedules 1, 2 and 3), Day 4 (Schedule 3 only), and Day 8 (Schedule 2 only): Pre-dose, and within 5 minutes, 1, 2, 4, and 8 hours post-dose (each Cycle length=21 days)

Notes
[36] - 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: Only descriptive data was planned.

End point values	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	1	1	4	6	4	5	5	3	3	3	6	3	7
Units: hours
geometric mean (geometric coefficient of variation)
C1D1 (n=1,1,4,6,4,5,5,3,3,3,6,3,7)	0.673 ( 99999 )	1.05 ( 99999 )	1.25 ( 102.0 )	1.10 ( 55.5 )	1.12 ( 45.7 )	0.807 ( 61.9 )	0.614 ( 29.1 )	0.682 ( 36.4 )	0.908 ( 75.2 )	0.705 ( 31.1 )	0.757 ( 64.2 )	0.536 ( 12.2 )	0.610 ( 24.1 )
C1D4 (n=0,0,0,0,0,0,0,0,3,3,4,3,5)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	1.21 ( 88.1 )	0.695 ( 33.9 )	0.917 ( 30.9 )	0.574 ( 14.5 )	1.04 ( 99.7 )
C1D8 (n=0,0,0,0,0,4,4,3,0,0,0,0,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	0.612 ( 19.8 )	0.707 ( 41.7 )	0.531 ( 10.6 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C2D1 (n=0,1,3,4,2,5,4,3,3,5,6,3,7)	9999 ( 9999 )	0.913 ( 99999 )	0.589 ( 1.6 )	0.748 ( 53.5 )	0.775 ( 37.3 )	0.747 ( 27.7 )	0.654 ( 34.5 )	0.526 ( 8.9 )	0.716 ( 48.5 )	0.754 ( 59.6 )	0.901 ( 130.6 )	1.00 ( 78.5 )	0.556 ( 9.4 )
C2D4 (n=0,0,0,0,0,0,0,0,3,4,4,3,5)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	0.901 ( 87.4 )	0.820 ( 86.3 )	0.991 ( 73.3 )	0.691 ( 33.2 )	0.596 ( 26.7 )
C2D8 (n=0,0,0,0,0,3,4,2,0,0,0,0,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	0.589 ( 4.3 )	0.572 ( 18.3 )	0.563 ( 16.8 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )

No statistical analyses for this end point

Secondary: Cohort 2, AUClast: Area Under the Serum Concentration–Time Curve From Zero Time to Time of Last Quantifiable Concentration of Nemvaleukin Alfa

Top of page

End point title

Cohort 2, AUClast: Area Under the Serum Concentration–Time Curve From Zero Time to Time of Last Quantifiable Concentration of Nemvaleukin Alfa ^[37]

End point description

End point type

Secondary

End point timeframe

Cycles 1 and 2: Day 1 (Schedules 1, 2 and 3), Day 4 (Schedule 3 only), and Day 8 (Schedule 2 only): Pre-dose, and within 5 minutes, 1, 2, 4, and 8 hours post-dose (each Cycle length=21 days)

Notes
[37] - 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: Only descriptive data was planned.

End point values	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	1	1	4	6	4	5	5	3	3	3	6	3	7
Units: hour micrograms per liter (h*mcg/L)
geometric mean (geometric coefficient of variation)
C1D1 (n=1,1,4,6,4,4,5,3,3,3,6,3,7)	677 ( 99999 )	1700 ( 99999 )	2870 ( 71.8 )	2120 ( 59.0 )	3790 ( 46.8 )	1180 ( 50.1 )	1560 ( 12.4 )	1860 ( 20.4 )	1490 ( 47.8 )	1780 ( 45.9 )	1790 ( 28.4 )	1770 ( 10.2 )	2620 ( 27.1 )
C1D4 (n=0,0,0,0,0,0,0,0,3,3,4,3,5)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	821 ( 32.0 )	1720 ( 50.2 )	1440 ( 30.0 )	1420 ( 17.4 )	2590 ( 24.6 )
C1D8 (n=0,0,0,0,0,4,4,3,0,0,0,0,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	1040 ( 65.1 )	1350 ( 6.5 )	1930 ( 33.1 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C2D1 (n=0,1,3,4,2,5,4,3,3,5,4,3,6)	9999 ( 9999 )	1520 ( 99999 )	2930 ( 35.9 )	2290 ( 67.2 )	2800 ( 59.2 )	987 ( 60.5 )	1390 ( 5.2 )	1600 ( 22.3 )	1560 ( 11.4 )	1360 ( 64.1 )	1290 ( 59.0 )	1670 ( 13.7 )	2490 ( 30.4 )
C2D4 (n=0,0,0,0,0,0,0,0,3,4,4,3,5)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	1860 ( 52.2 )	1280 ( 62.8 )	1100 ( 80.9 )	1590 ( 3.9 )	2210 ( 27.0 )
C2D8 (n=0,0,0,0,0,3,4,2,0,0,0,0,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	1190 ( 26.6 )	1150 ( 15.7 )	2100 ( 2.7 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )

No statistical analyses for this end point

Secondary: Cohort 2, Clast: Last Quantifiable Serum Concentration of Nemvaleukin Alfa

Top of page

End point title

Cohort 2, Clast: Last Quantifiable Serum Concentration of Nemvaleukin Alfa ^[38]

End point description

End point type

Secondary

End point timeframe

Cycles 1 and 2: Day 1 (Schedules 1, 2 and 3), Day 4 (Schedule 3 only), and Day 8 (Schedule 2 only): Pre-dose, and within 5 minutes, 1, 2, 4, and 8 hours post-dose (each Cycle length=21 days)

Notes
[38] - 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: Only descriptive data was planned.

End point values	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	1	1	5	6	4	5	5	3	3	3	6	3	7
Units: micrograms per liter (mcg/L)
geometric mean (geometric coefficient of variation)
C1D1 (n=1,1,5,6,4,5,5,3,3,5,6,3,7)	33.2 ( 99999 )	111 ( 99999 )	260 ( 61.8 )	96.4 ( 56.8 )	288 ( 48.4 )	98.3 ( 85.3 )	96.1 ( 16.7 )	106 ( 63.3 )	98.3 ( 84.1 )	107 ( 62.7 )	106 ( 20.7 )	74.4 ( 52.8 )	191 ( 48.1 )
C1D4 (n=0,0,0,0,0,0,0,0,3,3,4,3,5)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	80.0 ( 17.0 )	9999 ( 9999 )	9999 ( 9999 )	129 ( 37.9 )	77.0 ( 58.6 )	72.6 ( 30.7 )	54.5 ( 48.5 )	125 ( 38.8 )
C1D8 (n=0,0,0,0,0,4,4,3,0,0,0,0,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	62.7 ( 26.6 )	70.7 ( 9.6 )	92.4 ( 48.6 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C2D1 (n=0,1,3,4,2,5,4,3,3,5,4,3,6)	9999 ( 9999 )	68.7 ( 99999 )	244 ( 8.6 )	136 ( 140.0 )	176 ( 32.0 )	9999 ( 9999 )	81.7 ( 11.8 )	84.6 ( 37.2 )	87.0 ( 22.7 )	84.3 ( 62.2 )	86.1 ( 57.4 )	147 ( 59.7 )	153 ( 36.1 )
C2D4 (n=0,0,0,0,0,0,0,0,3,4,4,3,5)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	132 ( 132.7 )	76.9 ( 83.3 )	87.5 ( 98.5 )	111 ( 59.1 )	107 ( 37.0 )
C2D8 (n=0,0,0,0,0,5,5,3,0,0,0,0,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	84.5 ( 83.8 )	85.4 ( 50.6 )	117 ( 8.6 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )

No statistical analyses for this end point

Secondary: Cohort 2, Tlast: Time to the Last Quantifiable Concentration of Nemvaleukin Alfa

Top of page

End point title

Cohort 2, Tlast: Time to the Last Quantifiable Concentration of Nemvaleukin Alfa ^[39]

End point description

End point type

Secondary

End point timeframe

Cycles 1 and 2: Day 1 (Schedules 1, 2 and 3), Day 4 (Schedule 3 only), and Day 8 (Schedule 2 only): Pre-dose, and within 5 minutes, 1, 2, 4, and 8 hours post-dose (each Cycle length=21 days)

Notes
[39] - 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: Only descriptive data was planned.

End point values	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	1	1	5	6	4	5	5	3	3	3	6	3	7
Units: hours
geometric mean (geometric coefficient of variation)
C1D1 (n=1,1,5,6,4,5,5,3,3,3,6,3,7)	7.52 ( 99999 )	7.88 ( 99999 )	6.15 ( 34.7 )	7.81 ( 2.1 )	7.93 ( 3.7 )	5.51 ( 102.1 )	7.56 ( 13.0 )	7.95 ( 1.1 )	7.79 ( 3.6 )	7.87 ( 1.1 )	7.88 ( 5.8 )	7.91 ( 4.8 )	7.77 ( 4.7 )
C1D4 (n=0,0,0,0,0,0,0,0,3,3,4,3,5)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	5.09 ( 41.6 )	7.90 ( 1.7 )	7.93 ( 3.6 )	7.94 ( 2.1 )	7.95 ( 1.4 )
C1D8 (n=0,0,0,0,0,4,4,3,0,0,0,0,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	6.77 ( 33.0 )	7.96 ( 1.1 )	8.01 ( 0.1 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C2D1 (n=0,1,3,4,2,5,4,3,3,5,4,3,6)	9999 ( 9999 )	9999 ( 9999 )	6.99 ( 12.3 )	7.64 ( 3.1 )	7.89 ( 3.7 )	6.81 ( 32.8 )	7.96 ( 1.1 )	7.85 ( 3.0 )	7.31 ( 8.9 )	7.88 ( 1.4 )	6.67 ( 38.9 )	6.38 ( 40.9 )	7.68 ( 7.7 )
C2D4 (n=0,0,0,0,0,0,0,0,3,4,4,3,5)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	7.79 ( 3.5 )	7.95 ( 5.4 )	6.78 ( 33.4 )	7.76 ( 3.3 )	8.01 ( 1.2 )
C2D8 (n=0,0,0,0,0,3,4,2,0,0,0,0,0)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	7.84 ( 1.7 )	6.73 ( 31.9 )	7.87 ( 2.2 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )

No statistical analyses for this end point

Secondary: Number of Participants With Positive Anti-nemvaleukin Antibodies (ADA)

Top of page

End point title

Number of Participants With Positive Anti-nemvaleukin Antibodies (ADA)

End point description

Positive ADA were defined as sample with a positive result in the screen and the confirmatory assays. The immunogenicity population included all subjects who received at least one dose of nemvaleukin alfa and has a baseline and at least 1 post-treatment sample for ADA analysis.

End point type

Secondary

End point timeframe

Baseline up to 12 weeks for Cohort A; up to 39 weeks for Cohort 2

End point values	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	9	1	1	3	5	3	4	4	3	3	3	5	3	6
Units: participants	0	0	0	0	0	0	0	1	1	0	0	0	2	2

No statistical analyses for this end point

Secondary: Change From Baseline in Number of Total T Cells, CD8+ T Cells, CD56+ Cells, and Treg Cells in Peripheral Blood

Top of page

End point title

Change From Baseline in Number of Total T Cells, CD8+ T Cells, CD56+ Cells, and Treg Cells in Peripheral Blood

End point description

The circulating total T Cells, CD8+ T cells, CD56+ cells, and Treg cells in peripheral whole blood were measured using a validated biomarker assay. The peripheral blood PD population included subjects who received at least 1 dose of nemvaleukin alfa and had at least 1 post-baseline available peripheral blood PD measurement. Here, "number of subjects analyzed" signifies subjects who were evaluable for this endpoint and "n" signifies subjects who were evaluable at specified timepoints. Here, "99999" means data could not be calculated due to less subject and "9999” means data could not be evaluated as no subject was evaluated for the specified endpoint.

End point type

Secondary

End point timeframe

Cycle 1 Day 5; Cycle 2 Day 1; Cycle 3 Day 1 (each Cycle length = 21 days)

End point values	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	9	0 ^[40]	1	3	4	2	5	4	3	3	3	3	3	6
Units: cells count
arithmetic mean (standard deviation)
Total T:C1D5 (n=8,0,0,0,0,0,0,0,0,0,0,0,0,0)	-25.3 ( 231.55 )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
Total T:C2D1 (n=8,0,1,3,4,2,5,4,3,3,3,6,2,6)	224.8 ( 246.65 )	( )	29.0 ( 99999 )	14.3 ( 180.06 )	69.3 ( 92.10 )	-129.5 ( 338.70 )	-89.2 ( 61.92 )	236.8 ( 188.54 )	328.0 ( 392.49 )	370.3 ( 453.35 )	98.0 ( 277.64 )	140.3 ( 159.32 )	252.0 ( 26.87 )	459.8 ( 405.86 )
Total T:C3D1 (n=4,0,0,1,1,0,1,2,1,0,1,3,3,4)	-226.0 ( 99999 )	( )	9999 ( 9999 )	375.0 ( 99999 )	199.0 ( 99999 )	9999 ( 9999 )	619.0 ( 99999 )	307.0 ( 271.53 )	150.0 ( 99999 )	9999 ( 9999 )	55.0 ( 99999 )	267.7 ( 194.04 )	31.0 ( 660.80 )	324.8 ( 216.97 )
CD8+ T Cells:C1D5 (n=8,0,0,0,0,0,0,0,0,0,0,0,0,0)	-15.3 ( 84.27 )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
CD8+ T Cells:C2D1 (n=9,0,1,3,4,2,5,4,3,3,3,6,2,6)	117.0 ( 112.97 )	( )	8.0 ( 99999 )	161.0 ( 119.00 )	58.8 ( 48.82 )	-64.5 ( 222.74 )	-13.8 ( 58.94 )	144.8 ( 115.22 )	157.7 ( 122.60 )	160.0 ( 136.52 )	61.3 ( 20.53 )	81.7 ( 66.55 )	148.0 ( 53.74 )	226.5 ( 215.80 )
CD8+ T Cells:C3D1 (n=4,0,0,1,1,0,1,2,1,1,1,6,3,4)	42.5 ( 204.82 )	( )	9999 ( 9999 )	173.0 ( 99999 )	110.0 ( 99999 )	9999 ( 9999 )	524.0 ( 99999 )	191.0 ( 250.32 )	549.0 ( 99999 )	0 ( 99999 )	161.0 ( 99999 )	518.7 ( 338.54 )	99.3 ( 367.75 )	166.5 ( 107.07 )
CD56+ Cells:C1D5 (n=8,0,0,0,0,0,0,0,0,0,0,0,0,0)	156.9 ( 253.59 )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
CD56+ Cells:C2D1 (n=8,0,1,3,4,2,5,4,3,3,3,6,2,6)	294.1 ( 213.25 )	( )	6.0 ( 99999 )	166.0 ( 140.81 )	42.5 ( 57.23 )	133.0 ( 277.19 )	75.0 ( 46.73 )	267.8 ( 177.05 )	123.7 ( 76.49 )	82.0 ( 51.51 )	104.0 ( 62.22 )	110.2 ( 44.51 )	556.5 ( 792.67 )	280.8 ( 207.80 )
CD56+ Cells:C3D1 (n=4,0,0,1,1,0,1,2,1,0,1,3,3,4)	123.3 ( 167.07 )	( )	9999 ( 9999 )	239.0 ( 99999 )	-67.0 ( 99999 )	9999 ( 9999 )	653.0 ( 99999 )	584.0 ( 967.32 )	1284.0 ( 99999 )	9999 ( 9999 )	435.0 ( 99999 )	138.0 ( 23.81 )	-220.3 ( 604.21 )	303.0 ( 197.05 )
Treg:C1D5 (n=4,0,0,0,0,0,0,0,0,0,0,0,0,0)	14.7 ( 9.99 )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
Treg:C2D1 (n=8,0,1,1,4,2,4,4,3,3,3,5,3,6)	-0.7 ( 10.41 )	( )	8.4 ( 99999 )	-0.6 ( 99999 )	1.3 ( 6.25 )	-22.3 ( 30.78 )	3.3 ( 16.32 )	-0.1 ( 17.50 )	-5.0 ( 17.54 )	-10.4 ( 17.91 )	-11.8 ( 20.11 )	5.8 ( 15.61 )	-3.3 ( 8.94 )	4.6 ( 13.25 )
Treg:C3D1 (n=3,0,0,0,0,0,1,2,1,0,1,2,3,4)	-5.7 ( 5.91 )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	22.3 ( 99999 )	-9.3 ( 20.06 )	7.7 ( 99999 )	9999 ( 9999 )	-22.6 ( 99999 )	7.0 ( 6.85 )	-8.4 ( 8.68 )	-0.5 ( 6.88 )

Notes
[40] - No subjects were evaluable.

No statistical analyses for this end point

Secondary: Change From Baseline in Ratio of T Cells/Treg, CD8+/Treg, CD56+/Treg in Peripheral Blood

Top of page

End point title

Change From Baseline in Ratio of T Cells/Treg, CD8+/Treg, CD56+/Treg in Peripheral Blood

End point description

The circulating CD8+ T cells, Tregs, and NK cells in peripheral whole blood were measured using a validated biomarker assays and ratio of T Cells/Treg, CD8+/Treg, CD56+/Treg was calculated and reported. The peripheral blood PD population included subjects who received at least 1 dose of nemvaleukin alfa and had at least 1 post-baseline available peripheral blood PD measurement. Here, "number of subjects analyzed" signifies subjects who were evaluable for this endpoint and "n" signifies subjects who were evaluable at specified timepoints. Here, "99999" means data could not be calculated due to less subject and "9999” means data could not be evaluated as no subject was evaluated for the specified endpoint.

End point type

Secondary

End point timeframe

Cycle 1 Day 5; Cycle 2 Day 1; Cycle 3 Day 1 (each Cycle length = 21 days)

End point values	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	8	0 ^[41]	1	1	4	3	4	4	3	3	3	5	3	6
Units: ratio
arithmetic mean (standard deviation)
T/Treg:C1D5 (n=4,0,0,0,0,0,0,0,0,0,0,0,0,0)	-19.5 ( 15.90 )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
T/Treg:C2D1 (n=8,0,1,1,4,2,4,4,3,3,3,5,2,6)	25.6 ( 25.50 )	( )	-22.5 ( 99999 )	11.9 ( 99999 )	-78.9 ( 170.65 )	26.2 ( 56.16 )	34.9 ( 208.05 )	7.1 ( 21.31 )	1.0 ( 96.36 )	105.4 ( 159.69 )	-382.1 ( 1019.06 )	-17.5 ( 47.99 )	5.5 ( 10.32 )	15.4 ( 28.86 )
T/Treg:C3D1 (n=3,0,0,0,0,0,1,2,1,0,1,2,3,4)	12.8 ( 9.96 )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	-89.3 ( 99999 )	33.8 ( 58.63 )	21.2 ( 99999 )	9999 ( 9999 )	264.3 ( 99999 )	17.3 ( 0.33 )	333.2 ( 589.70 )	28.6 ( 33.91 )
CD8+/Treg:C1D5 (n=4,0,0,0,0,0,0,0,0,0,0,0,0,0)	-6.5 ( 6.26 )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
CD8+/Treg:C2D1 (n=8,0,1,1,4,3,4,4,3,3,3,5,2,6)	9.8 ( 9.61 )	( )	-5.9 ( 99999 )	3.6 ( 99999 )	23.4 ( 57.43 )	3.8 ( 16.98 )	30.1 ( 120.44 )	6.5 ( 6.15 )	-7.6 ( 46.42 )	39.2 ( 52.39 )	-166.3 ( 380.84 )	-2.9 ( 19.58 )	4.1 ( 7.03 )	9.2 ( 13.48 )
CD8+/Treg:C3D1 (n=3,0,0,0,0,0,1,2,1,0,1,2,3,4)	7.5 ( 9.78 )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	-35.8 ( 99999 )	10.4 ( 15.70 )	9.8 ( 99999 )	9999 ( 9999 )	59.7 ( 99999 )	10.1 ( 0.68 )	182.8 ( 319.89 )	11.2 ( 11.08 )
CD56+/Treg:C1D5 (n=4,0,0,0,0,0,0,0,0,0,0,0,0,0)	1.8 ( 9.25 )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
CD56+/Treg:C2D1 (n=8,0,1,1,4,2,4,4,3,3,3,5,2,6)	21.2 ( 15.65 )	( )	-7.4 ( 99999 )	11.4 ( 99999 )	-11.3 ( 33.71 )	12.3 ( 20.76 )	45.5 ( 112.43 )	10.5 ( 5.16 )	0.8 ( 34.35 )	14.2 ( 12.09 )	7.3 ( 109.52 )	3.1 ( 14.01 )	10.8 ( 15.01 )	15.0 ( 19.08 )
CD56+/Treg:C3D1 (n=3,0,0,0,0,0,1,2,1,0,1,2,3,4)	10.8 ( 8.57 )	( )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	-4.7 ( 99999 )	10.0 ( 2.73 )	1.8 ( 99999 )	9999 ( 9999 )	286.8 ( 99999 )	5.1 ( 5.37 )	101.7 ( 184.75 )	19.9 ( 14.82 )

Notes
[41] - No subjects were evaluable.

No statistical analyses for this end point

Secondary: Change From Baseline in Absolute Numbers of Circulating Leukocytes Subtypes Cells

Top of page

End point title

Change From Baseline in Absolute Numbers of Circulating Leukocytes Subtypes Cells

End point description

The interpretation of the TME data was limited by the small sample size in individual cohorts and schedules and by the wide variability in expression of the biomarkers. Since it was planned to not summarize data when number of samples is small. Therefore, the data was not summarized and reported in this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 39

Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg

Number of subjects analysed

0 ^[42]

0 ^[43]

0 ^[44]

0 ^[45]

0 ^[46]

0 ^[47]

0 ^[48]

0 ^[49]

0 ^[50]

0 ^[51]

0 ^[52]

0 ^[53]

0 ^[54]

0 ^[55]

Units: participants

Notes
[42] - No subject was evaluated.
[43] - No subject was evaluated.
[44] - No subject was evaluated.
[45] - No subject was evaluated.
[46] - No subject was evaluated.
[47] - No subject was evaluated.
[48] - No subject was evaluated.
[49] - No subject was evaluated.
[50] - No subject was evaluated.
[51] - No subject was evaluated.
[52] - No subject was evaluated.
[53] - No subject was evaluated.
[54] - No subject was evaluated.
[55] - No subject was evaluated.

No statistical analyses for this end point

Secondary: Serum Concentrations of Interferon Gamma (IFN-γ), Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1 Beta, IL-6, and IL-10 Cytokines

Top of page

End point title

Serum Concentrations of Interferon Gamma (IFN-γ), Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1 Beta, IL-6, and IL-10 Cytokines

End point description

Serum concentrations of IFN-γ, TNF-α, IL-1 beta, IL-6, and IL-10 were determined using a validated soluble protein assay kit. Here, in timeframe 'C' stands for Cycle, 'D' for Day and 'h' for hours. Cycle 1 length was 14 days and length of other specified cycle was 21 days. The peripheral blood PD population included subjects who received at least 1 dose of nemvaleukin alfa and had at least 1 post-baseline available peripheral blood PD measurement. Here, "Number Analyzed" signifies subjects evaluable at given timepoints. "99999" means data could not be estimated due to insufficient events. “9999” means data could not be evaluated as no subject was evaluated.

End point type

Secondary

End point timeframe

Cycle 1 Day 1: Pre-dose, 4 and 8 hours post-dose; Cycle 1 Day 8 (Cycle length = 21 days)

End point values	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Number of subjects analysed	9	1	1	2	5	4	5	5	3	3	3	3	3	6
Units: picograms per milliters (pg/mL)
arithmetic mean (standard deviation)
IFN-γ:C1D1:Pre dose(n=9,1,1,1,2,1,5,5,3,1,3,6,3,6)	9.5 ( 5.84 )	15.0 ( 99999 )	4.9 ( 9999 )	27.7 ( 99999 )	9.5 ( 10.85 )	2.7 ( 99999 )	4.9 ( 3.19 )	7.0 ( 3.46 )	7.7 ( 1.87 )	11.7 ( 99999 )	33.0 ( 45.51 )	7.3 ( 5.57 )	7.4 ( 5.40 )	19.7 ( 30.84 )
IFN-γ:C1D1:4h PD(n=9,1,1,2,2,1,4,5,3,1,3,6,3,6)	1263.2 ( 1114.35 )	1925.7 ( 99999 )	4968.0 ( 99999 )	3990.1 ( 3714.49 )	1442.0 ( 256.73 )	2825.2 ( 99999 )	737.0 ( 403.60 )	2841.2 ( 2548.13 )	3405.2 ( 2386.54 )	2813.0 ( 99999 )	2081.5 ( 1625.63 )	1690.3 ( 1188.49 )	1883.1 ( 711.64 )	3309.7 ( 1431.11 )
IFN-γ:C1D1:8h PD(n=0,1,1,1,2,1,4,5,3,1,3,6,3,6)	9999 ( 9999 )	653.4 ( 99999 )	852.4 ( 99999 )	11483.0 ( 99999 )	467.9 ( 391.92 )	6018.8 ( 99999 )	293.4 ( 99.52 )	1578.0 ( 1700.82 )	1345.0 ( 774.61 )	1316.1 ( 99999 )	3340.6 ( 3302.24 )	1738.7 ( 1928.47 )	1568.8 ( 244.11 )	2586.2 ( 1800.74 )
IFN-γ:C1D8(n=6,0,0,0,0,0,0,0,0,0,0,0,1,6)	20.0 ( 7.22 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	5.2 ( 99999 )	78.7 ( 115.98 )
IL-10 :C1D1:Predose(n=9,1,1,1,2,1,5,5,3,1,3,6,3,6)	1.9 ( 0.75 )	1.6 ( 99999 )	1.6 ( 99999 )	1.6 ( 99999 )	1.7 ( 0.05 )	1.6 ( 99999 )	1.6 ( 0.00 )	1.6 ( 0.00 )	1.6 ( 0.00 )	1.6 ( 99999 )	1.6 ( 0.00 )	1.6 ( 0.00 )	1.6 ( 0.00 )	2.0 ( 0.82 )
IL-10 :C1D1:4h PD(n=9,1,1,2,2,1,5,5,3,1,3,6,3,6)	5.0 ( 8.69 )	3.8 ( 99999 )	1.6 ( 99999 )	3.9 ( 3.03 )	4.7 ( 0.95 )	1.8 ( 99999 )	2.7 ( 0.78 )	2.7 ( 1.04 )	1.9 ( 0.56 )	2.0 ( 99999 )	2.0 ( 0.54 )	2.2 ( 0.52 )	2.9 ( 0.75 )	7.0 ( 10.20 )
IL-10 :C1D1:8h PD(n=0,1,1,1,2,1,4,5,3,1,3,6,3,6)	9999 ( 9999 )	7.4 ( 99999 )	2.9 ( 99999 )	12.1 ( 99999 )	10.6 ( 1.73 )	4.6 ( 99999 )	8.5 ( 5.22 )	7.2 ( 4.55 )	5.8 ( 2.24 )	3.3 ( 99999 )	9.4 ( 5.33 )	14.1 ( 17.55 )	11.8 ( 10.11 )	14.1 ( 9.63 )
IL-10 :C1D8(n=6,0,0,0,0,0,0,0,0,0,0,1,0,6)	1.6 ( 0.00 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	1.6 ( 99999 )	9999 ( 9999 )	1.7 ( 0.08 )
IL1beta:C1D1Predose(n=9,1,1,1,2,1,5,5,3,1,3,6,3,6)	3.0 ( 0.00 )	3.0 ( 99999 )	3.0 ( 99999 )	3.0 ( 99999 )	3.0 ( 0.00 )	3.0 ( 99999 )	3.0 ( 0.00 )	3.1 ( 0.27 )	3.0 ( 0.00 )	3.0 ( 99999 )	3.0 ( 0.00 )	3.0 ( 0.00 )	3.0 ( 0.00 )	3.0 ( 0.00 )
IL1beta:C1D1:4h PD(n=9,1,1,2,2,1,4,5,3,1,3,6,3,6)	3.0 ( 0.00 )	3.0 ( 99999 )	3.0 ( 99999 )	3.0 ( 0.00 )	3.0 ( 0.00 )	3.0 ( 99999 )	3.0 ( 0.00 )	3.4 ( 0.76 )	3.0 ( 0.00 )	3.0 ( 99999 )	3.0 ( 0.00 )	3.0 ( 0.00 )	3.0 ( 0.00 )	3.0 ( 0.00 )
IL1beta:C1D1:8h PD(n=0,1,1,1,2,1,4,5,3,1,3,6,3,6)	9999 ( 9999 )	3.0 ( 99999 )	3.0 ( 99999 )	3.0 ( 99999 )	3.0 ( 0.00 )	3.0 ( 99999 )	3.0 ( 0.00 )	3.0 ( 0.00 )	3.0 ( 0.00 )	3.0 ( 99999 )	3.0 ( 0.00 )	3.0 ( 0.00 )	3.0 ( 0.00 )	3.0 ( 0.00 )
IL1beta:C1D8(n=6,0,0,0,0,0,0,0,0,0,0,0,0,0)	3.0 ( 0.00 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
IL-6:C1D1:Predose(n=9,1,1,1,2,1,5,5,3,1,3,6,3,6)	7.5 ( 5.88 )	10.8 ( 99999 )	2.0 ( 99999 )	7.6 ( 99999 )	27.4 ( 28.63 )	1.5 ( 99999 )	8.3 ( 10.97 )	5.7 ( 4.57 )	6.7 ( 8.25 )	1.4 ( 99999 )	4.2 ( 3.33 )	6.9 ( 13.79 )	2.2 ( 0.51 )	5.8 ( 3.68 )
IL-6:C1D1:4h PD(n=9,1,1,2,2,1,4,5,3,1,3,6,3,6)	156.4 ( 188.57 )	274.7 ( 99999 )	363.5 ( 99999 )	475.2 ( 208.66 )	544.8 ( 699.65 )	595.7 ( 99999 )	267.7 ( 418.09 )	293.4 ( 192.88 )	228.0 ( 190.51 )	125.7 ( 99999 )	104.1 ( 84.93 )	163.9 ( 156.06 )	137.9 ( 74.25 )	287.6 ( 147.72 )
IL-6:C1D1:8h PD(n=0,1,1,1,2,1,4,5,3,1,3,6,3,6)	9999 ( 9999 )	40.9 ( 99999 )	37.9 ( 99999 )	566.2 ( 99999 )	90.6 ( 78.29 )	298.4 ( 99999 )	91.5 ( 86.72 )	184.9 ( 265.79 )	81.6 ( 58.64 )	26.2 ( 99999 )	227.4 ( 169.43 )	321.5 ( 522.63 )	107.8 ( 57.89 )	223.0 ( 196.59 )
IL-6:C1D8(n=6,0,0,0,0,0,0,0,0,0,0,0,0,0)	6.2 ( 4.70 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
TNF-α:C1D1:Predose(n=9,1,1,2,5,4,5,5,3,3,3,6,3,6)	4.6 ( 1.77 )	2.8 ( 99999 )	1.1 ( 99999 )	4.7 ( 2.36 )	3.5 ( 0.97 )	2.0 ( 0.25 )	2.8 ( 0.94 )	3.3 ( 2.25 )	2.8 ( 0.79 )	2.7 ( 0.40 )	4.1 ( 1.65 )	2.3 ( 0.73 )	2.3 ( 0.57 )	2.4 ( 0.92 )
TNF-α:C1D1:4h PD(n=0,1,1,3,5,4,4,5,3,3,3,6,3,6)	9999 ( 9999 )	9.5 ( 99999 )	11.3 ( 99999 )	10.2 ( 8.44 )	15.1 ( 7.58 )	23.2 ( 10.50 )	9.4 ( 2.50 )	16.8 ( 4.74 )	15.4 ( 1.78 )	13.9 ( 7.35 )	14.3 ( 3.58 )	14.8 ( 9.52 )	15.9 ( 4.88 )	16.1 ( 6.86 )
TNF-α:C1D1:8h PD(n=0,1,1,2,5,4,4,5,3,3,3,6,3,1)	9999 ( 9999 )	5.8 ( 99999 )	4.7 ( 99999 )	19.8 ( 2.54 )	15.66 ( 11.37 )	16.6 ( 4.42 )	9.2 ( 3.23 )	13.0 ( 3.63 )	13.5 ( 3.79 )	10.3 ( 3.38 )	25.0 ( 12.71 )	17.5 ( 17.58 )	14.9 ( 6.05 )	15.5 ( 99999 )
TNF-α:C1D8(n=6,0,0,0,0,0,0,0,0,0,0,1,0,6)	6.7 ( 3.04 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	1.7 ( 99999 )	9999 ( 9999 )	3.2 ( 1.09 )

No statistical analyses for this end point

Secondary: Cohort 1: Change From Baseline in Density of Immune Cells: Total T Cells, CD8+ T Cells, CD56+ Cells, and Tregs in Tumor Biopsies

Top of page

End point title

Cohort 1: Change From Baseline in Density of Immune Cells: Total T Cells, CD8+ T Cells, CD56+ Cells, and Tregs in Tumor Biopsies ^[56]

End point description

TME-evaluable population. As pre-specified in protocol, tumor biopsies were optional at Day 8 of Cycles 4 and 5, and these optional assessments were not performed. Hence, no data was collected to be reported in this outcome measure.

End point type

Secondary

End point timeframe

Baseline, at Day 8 of Cycles 4 and 5 (each Cycle length=21 days)

Notes
[56] - 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: Only descriptive data was planned.

End point values	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Number of subjects analysed	0 ^[57]
Units: participants

Notes
[57] - No subjects evaluated for this endpoint

No statistical analyses for this end point

Secondary: Cohort 1: Change From Baseline in Ratio of T/Treg, CD8+/Treg, CD56+/Tregs in Tumor Biopsies

Top of page

End point title

Cohort 1: Change From Baseline in Ratio of T/Treg, CD8+/Treg, CD56+/Tregs in Tumor Biopsies ^[58]

End point description

End point type

Secondary

End point timeframe

Baseline, at Day 8 of Cycle 4 and 5 (each Cycle length=21 days)

Notes
[58] - 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: Only descriptive data was planned.

End point values	Cohort 1: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Number of subjects analysed	0 ^[59]
Units: ratio
arithmetic mean (standard deviation)	( )

Notes
[59] - no data was collected to be reported in this endpoint.

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From first dose of study drug up to 30 days after last dose (up to 16 weeks for Cohort 1; up to 43 weeks for Cohort 2)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

Cohort 1, Monotherapy: Nemvaleukin Alfa 6 mcg/kg

Reporting group description

Subjects received nemvaleukin alfa 6 mcg/kg, IV infusion, once daily for 5 consecutive days, followed by 9 days off during Cycle 1 (Cycle 1 length=14 days) and 16 days off during Cycle 2 (Cycle 2 length=21 days).

Reporting group title

Cohort 1, Combination: Nemvaleukin Alfa 6 mcg/kg+Pembrolizumab

Reporting group description

Subjects received nemvaleukin alfa 6 mcg/kg, as a single dose, IV infusion, on Day 1 of each 21-day cycle in combination with pembrolizumab 200 mg, IV infusion until subjects deriving clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg

Reporting group description

Subjects received nemvaleukin alfa 10 mcg/kg, IV infusion, once on Day 1 of each 21-day cycle until subjects deriving clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg

Reporting group description

Subjects received nemvaleukin alfa 30 mcg/kg, IV infusion, once on Day 1 of each 21-day cycle until subjects deriving clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg

Reporting group description

Subjects received nemvaleukin alfa 35 mcg/kg, IV infusion, once on Day 1 of each 21-day cycle until subjects deriving clinical benefit (i.e., stable disease or better) or they met any other discontinuation criteria.

Reporting group title

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg

Reporting group description

Reporting group title

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg

Reporting group description

Cohort 1, Monotherapy: Nemvaleukin Alfa 6 mcg/kg

Cohort 1, Combination: Nemvaleukin Alfa 6 mcg/kg+Pembrolizumab

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg

Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg

Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg

Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg

Total subjects affected by serious adverse events

subjects affected / exposed

2 / 9 (22.22%)

1 / 4 (25.00%)

1 / 1 (100.00%)

2 / 5 (40.00%)

1 / 6 (16.67%)

2 / 4 (50.00%)

2 / 5 (40.00%)

3 / 5 (60.00%)

2 / 3 (66.67%)

0 / 3 (0.00%)

1 / 3 (33.33%)

2 / 6 (33.33%)

1 / 3 (33.33%)

3 / 7 (42.86%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tumour associated fever

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Vascular disorders

Haemorrhage

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Immune system disorders

Cytokine release syndrome

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Dyspnoea

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

2 / 5 (40.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory disorder

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

occurrences causally related to treatment / all

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

0 / 1

Investigations

Capillary permeability increased

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Heat exhaustion

subjects affected / exposed

1 / 9 (11.11%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fall

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Pericardial effusion

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Cerebral haemorrhage

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Headache

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

1 / 1 (100.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Uraemic encephalopathy

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

1 / 9 (11.11%)

1 / 4 (25.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

1 / 9 (11.11%)

1 / 4 (25.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

1 / 9 (11.11%)

1 / 4 (25.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

Photosensitivity reaction

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Lumbar spinal stenosis

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

1 / 1 (100.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Pneumonia

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Device related infection

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia escherichia

subjects affected / exposed

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Cohort 1, Monotherapy: Nemvaleukin Alfa 6 mcg/kg	Cohort 1, Combination: Nemvaleukin Alfa 6 mcg/kg+Pembrolizumab	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 10 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 35 mcg/kg	Cohort 2, Part A, Schedule 1: Nemvaleukin Alfa 40 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 2: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 15 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 20 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 25 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 30 mcg/kg	Cohort 2, Part A, Schedule 3: Nemvaleukin Alfa 35 mcg/kg
Total subjects affected by non serious adverse events
subjects affected / exposed	9 / 9 (100.00%)	4 / 4 (100.00%)	1 / 1 (100.00%)	1 / 1 (100.00%)	4 / 5 (80.00%)	6 / 6 (100.00%)	4 / 4 (100.00%)	5 / 5 (100.00%)	5 / 5 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)	3 / 3 (100.00%)	7 / 7 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to peritoneum
subjects affected / exposed	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Tumour pain
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cancer pain
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Vascular disorders
Hypertension
subjects affected / exposed	4 / 9 (44.44%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pelvic venous thrombosis
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypotension
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	2 / 6 (33.33%)	0 / 3 (0.00%)	2 / 7 (28.57%)
occurrences all number	0	0	0	0	0	1	1	1	0	0	0	3	3	0	3
General disorders and administration site conditions
Fatigue
subjects affected / exposed	4 / 9 (44.44%)	2 / 4 (50.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	2 / 5 (40.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)	3 / 6 (50.00%)	1 / 3 (33.33%)	2 / 7 (28.57%)
occurrences all number	4	2	0	0	1	2	1	2	3	0	2	1	5	1	2
Chills
subjects affected / exposed	5 / 9 (55.56%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 3 (33.33%)	1 / 7 (14.29%)
occurrences all number	9	0	0	0	0	1	2	0	0	0	0	1	3	2	1
Pyrexia
subjects affected / exposed	3 / 9 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	2 / 5 (40.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	2 / 3 (66.67%)	2 / 7 (28.57%)
occurrences all number	4	0	0	0	0	0	1	2	1	0	0	1	1	3	4
Oedema peripheral
subjects affected / exposed	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)
occurrences all number	2	0	0	0	0	0	0	2	1	0	2	0	0	0	1
Asthenia
subjects affected / exposed	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	1	0	0	0	0	0	1	0	0	0	0	3	0	1
Catheter site pain
subjects affected / exposed	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Early satiety
subjects affected / exposed	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Peripheral swelling
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Immune system disorders
Cytokine release syndrome
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 5 (0.00%)	2 / 6 (33.33%)	2 / 4 (50.00%)	2 / 5 (40.00%)	0 / 5 (0.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 6 (33.33%)	0 / 3 (0.00%)	3 / 7 (42.86%)
occurrences all number	0	0	0	1	0	2	2	3	0	2	3	2	4	0	8
Reproductive system and breast disorders
Vulvovaginal burning sensation
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vulvovaginal pruritus
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	3 / 9 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Dyspnoea
subjects affected / exposed	1 / 9 (11.11%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	2	0	0	0	1	0	0	2	0	2	0	1	0	0
Pleural effusion
subjects affected / exposed	1 / 9 (11.11%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	2	0	0	0	1	0	0	1	0	0	0	0	0	0
Bronchostenosis
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory tract congestion
subjects affected / exposed	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	2	0	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Epistaxis
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Hypoxia
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	5 / 9 (55.56%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	2 / 5 (40.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	3 / 6 (50.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)
occurrences all number	10	0	0	0	2	0	0	0	0	0	1	0	4	2	0
Alanine aminotransferase increased
subjects affected / exposed	4 / 9 (44.44%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	2 / 5 (40.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 6 (50.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)
occurrences all number	6	0	0	0	2	0	0	0	0	0	0	0	4	1	0
Blood creatinine increased
subjects affected / exposed	3 / 9 (33.33%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	5	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0	0	1	0	0	0	0	0	0	0	0	0	0
White blood cell count decreased
subjects affected / exposed	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	4	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Bacterial test positive
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Electrocardiogram PR prolongation
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Electrocardiogram QT prolonged
subjects affected / exposed	1 / 9 (11.11%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0
Eastern Cooperative Oncology Group performance status
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Bilirubin conjugated increased
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 9 (0.00%)	2 / 4 (50.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 3 (33.33%)	0 / 7 (0.00%)
occurrences all number	0	2	0	0	0	0	1	1	1	0	0	1	1	1	0
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 1 (100.00%)	1 / 1 (100.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 5 (20.00%)	3 / 5 (60.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 3 (66.67%)	1 / 6 (16.67%)	1 / 3 (33.33%)	2 / 7 (28.57%)
occurrences all number	0	0	1	1	0	1	0	1	3	4	0	2	3	2	3
Fall
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Cardiac disorders
Tachycardia
subjects affected / exposed	5 / 9 (55.56%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	8	1	0	0	0	0	0	0	0	0	2	0	6	0	0
Bradycardia
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	4 / 9 (44.44%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 7 (14.29%)
occurrences all number	5	0	0	0	0	0	0	1	0	0	0	0	1	0	1
Hypoaesthesia
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dizziness
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Dysgeusia
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Seizure
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Somnolence
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Lymphopenia
subjects affected / exposed	7 / 9 (77.78%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 7 (14.29%)
occurrences all number	22	0	0	0	0	2	0	0	0	0	1	0	1	0	1
Anaemia
subjects affected / exposed	4 / 9 (44.44%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	4	1	0	0	1	0	1	3	0	0	1	0	1	0	0
Neutropenia
subjects affected / exposed	4 / 9 (44.44%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 6 (50.00%)	2 / 3 (66.67%)	1 / 7 (14.29%)
occurrences all number	6	0	0	0	1	0	0	0	0	0	0	0	4	3	1
Leukopenia
subjects affected / exposed	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Thrombocytopenia
subjects affected / exposed	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)
occurrences all number	6	0	0	0	1	0	0	1	0	0	0	1	0	1	0
Eosinophilia
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Leukocytosis
subjects affected / exposed	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0
Thrombocytosis
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Nausea
subjects affected / exposed	3 / 9 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	3 / 5 (60.00%)	1 / 6 (16.67%)	2 / 4 (50.00%)	0 / 5 (0.00%)	2 / 5 (40.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)	0 / 3 (0.00%)	2 / 7 (28.57%)
occurrences all number	4	0	0	0	4	1	4	0	2	1	0	3	4	0	3
Abdominal distension
subjects affected / exposed	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Abdominal pain
subjects affected / exposed	0 / 9 (0.00%)	2 / 4 (50.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	3 / 6 (50.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	3	0	0	1	3	0	1	0	0	0	0	0	0	0
Abdominal pain upper
subjects affected / exposed	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Diarrhoea
subjects affected / exposed	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Anal haemorrhage
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Ascites
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0	0	0	0	0	2	1	0	0	0	0	0	0
Constipation
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	1	2	0	0	0	0	0	0	0	0	0
Haemorrhoids
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Large intestinal obstruction
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Retching
subjects affected / exposed	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Stomatitis
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vomiting
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	3 / 5 (60.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	4	1	2	1	1	0	0	0	0	0	0
Dyspepsia
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1
Skin and subcutaneous tissue disorders
Night sweats
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hyperhidrosis
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Pruritus
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Angioedema
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Photosensitivity reaction
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Haematuria
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Urinary tract disorder
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Muscle spasms
subjects affected / exposed	1 / 9 (11.11%)	2 / 4 (50.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	0	0	0	0	0	0
Muscular weakness
subjects affected / exposed	1 / 9 (11.11%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Myalgia
subjects affected / exposed	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Flank pain
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal stiffness
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Myopathy
subjects affected / exposed	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Neck pain
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Muscle atrophy
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Infections and infestations
COVID-19
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Cellulitis
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Clostridium difficile colitis
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Viral infection
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 7 (28.57%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	2
Pneumonia
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	2 / 9 (22.22%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 3 (33.33%)	0 / 7 (0.00%)
occurrences all number	2	1	0	0	0	1	1	0	0	0	0	0	2	1	0
Hyperuricaemia
subjects affected / exposed	2 / 9 (22.22%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)
occurrences all number	3	1	0	0	0	1	1	0	0	0	0	0	0	0	0
Appetite disorder
subjects affected / exposed	1 / 9 (11.11%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Hyperkalaemia
subjects affected / exposed	2 / 9 (22.22%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypoalbuminaemia
subjects affected / exposed	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0	0	0	0	0	1	0	0	1	0	1	0	0
Hyponatraemia
subjects affected / exposed	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0	0	0	0	0	1	0	0	1	0	1	0	0
Hypocalcaemia
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypokalaemia
subjects affected / exposed	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	2 / 5 (40.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)
occurrences all number	1	0	0	0	2	1	0	0	0	0	0	1	0	0	1
Malnutrition
subjects affected / exposed	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	2 / 5 (40.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	1	0	0	2	1	0	0	0	0	0	1	0	0	1
Dehydration
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 5 (20.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0
Hypercalcaemia
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Hypomagnesaemia
subjects affected / exposed	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

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

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Clinical and Immunologic Activity of Nemvaleukin Alfa With a Less Frequent IV Dosing Schedule as Monotherapy and in Combination With Pembrolizumab and Impact on Tumor Microenvironment in Solid Tumor Patients (ARTISTRY-3)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Cohort 1: Change From Baseline in Density of Immune Cells: Total T Cells, Cluster of Differentiation (CD)8+ T Cells, CD56+ Cells, and Regulatory T Cells (Tregs) at Cycle 2 Day 8 in Paired Tumor Biopsies

Primary: Cohort 1: Change From Baseline in Density of Immune Cells: Total T Cells, Cluster of Differentiation (CD)8+ T Cells, CD56+ Cells, and Regulatory T Cells (Tregs) at Cycle 2 Day 8 in Paired Tumor Biopsies

Primary: Cohort 1: Change From Baseline in Ratio of T/Treg, CD8+/Treg, CD56+/Tregs at Cycle 2 Day 8 in Paired Tumor Biopsies

Primary: Cohort 1: Change From Baseline in Ratio of T/Treg, CD8+/Treg, CD56+/Tregs at Cycle 2 Day 8 in Paired Tumor Biopsies

Primary: Cohort 2 (Less Frequent IV Dosing): Number of Participants With of Dose-limiting Toxicity (DLT)

Primary: Cohort 2 (Less Frequent IV Dosing): Number of Participants With of Dose-limiting Toxicity (DLT)

Secondary: Overall Response Rate (ORR) Based on RECIST 1.1

Secondary: Overall Response Rate (ORR) Based on RECIST 1.1

Secondary: Overall Response Rate (ORR) Based on iRECIST

Secondary: Overall Response Rate (ORR) Based on iRECIST

Secondary: Duration of Response (DOR) Among Confirmed Responders Based on RECIST 1.1

Secondary: Duration of Response (DOR) Among Confirmed Responders Based on RECIST 1.1

Secondary: Duration of Response (DOR) Among Confirmed Responders Based on iRECIST 1.1

Secondary: Duration of Response (DOR) Among Confirmed Responders Based on iRECIST 1.1

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and TEAEs Severity Grade 3 or Higher

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and TEAEs Severity Grade 3 or Higher

Secondary: Number of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs Values

Secondary: Number of Participants With Potentially Clinically Significant Change From Baseline in Vital Signs Values

Secondary: Number of Participants With Clinically Significant Abnormal Changes From Baseline in Laboratory Tests

Secondary: Number of Participants With Clinically Significant Abnormal Changes From Baseline in Laboratory Tests

Secondary: Number of Participants With Clinically Significant Change From Baseline in Electrocardiograms (ECGs) Values

Secondary: Number of Participants With Clinically Significant Change From Baseline in Electrocardiograms (ECGs) Values

Secondary: Cohort 1: Concentrations of Nemvaleukin in Serum

Secondary: Cohort 1: Concentrations of Nemvaleukin in Serum

Secondary: Cohort 2: Concentrations of Nemvaleukin in Serum

Secondary: Cohort 2: Concentrations of Nemvaleukin in Serum

Secondary: Cohort 2, Cmax: Maximum Observed Serum Concentration of Nemvaleukin Alfa

Secondary: Cohort 2, Cmax: Maximum Observed Serum Concentration of Nemvaleukin Alfa

Secondary: Cohort 2, Tmax: Time to Reach Cmax of Nemvaleukin Alfa

Secondary: Cohort 2, Tmax: Time to Reach Cmax of Nemvaleukin Alfa

Secondary: Cohort 2, AUClast: Area Under the Serum Concentration–Time Curve From Zero Time to Time of Last Quantifiable Concentration of Nemvaleukin Alfa

Secondary: Cohort 2, AUClast: Area Under the Serum Concentration–Time Curve From Zero Time to Time of Last Quantifiable Concentration of Nemvaleukin Alfa

Secondary: Cohort 2, Clast: Last Quantifiable Serum Concentration of Nemvaleukin Alfa

Secondary: Cohort 2, Clast: Last Quantifiable Serum Concentration of Nemvaleukin Alfa

Secondary: Cohort 2, Tlast: Time to the Last Quantifiable Concentration of Nemvaleukin Alfa

Secondary: Cohort 2, Tlast: Time to the Last Quantifiable Concentration of Nemvaleukin Alfa

Secondary: Number of Participants With Positive Anti-nemvaleukin Antibodies (ADA)

Secondary: Number of Participants With Positive Anti-nemvaleukin Antibodies (ADA)

Secondary: Change From Baseline in Number of Total T Cells, CD8+ T Cells, CD56+ Cells, and Treg Cells in Peripheral Blood

Secondary: Change From Baseline in Number of Total T Cells, CD8+ T Cells, CD56+ Cells, and Treg Cells in Peripheral Blood

Secondary: Change From Baseline in Ratio of T Cells/Treg, CD8+/Treg, CD56+/Treg in Peripheral Blood

Secondary: Change From Baseline in Ratio of T Cells/Treg, CD8+/Treg, CD56+/Treg in Peripheral Blood

Secondary: Change From Baseline in Absolute Numbers of Circulating Leukocytes Subtypes Cells

Secondary: Change From Baseline in Absolute Numbers of Circulating Leukocytes Subtypes Cells

Secondary: Serum Concentrations of Interferon Gamma (IFN-γ), Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1 Beta, IL-6, and IL-10 Cytokines

Secondary: Serum Concentrations of Interferon Gamma (IFN-γ), Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1 Beta, IL-6, and IL-10 Cytokines

Secondary: Cohort 1: Change From Baseline in Density of Immune Cells: Total T Cells, CD8+ T Cells, CD56+ Cells, and Tregs in Tumor Biopsies

Secondary: Cohort 1: Change From Baseline in Density of Immune Cells: Total T Cells, CD8+ T Cells, CD56+ Cells, and Tregs in Tumor Biopsies

Secondary: Cohort 1: Change From Baseline in Ratio of T/Treg, CD8+/Treg, CD56+/Tregs in Tumor Biopsies

Secondary: Cohort 1: Change From Baseline in Ratio of T/Treg, CD8+/Treg, CD56+/Tregs in Tumor Biopsies

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Clinical and Immunologic Activity of Nemvaleukin Alfa With a Less Frequent IV Dosing Schedule as Monotherapy and in Combination With Pembrolizumab and Impact on Tumor Microenvironment in Solid Tumor Patients (ARTISTRY-3)