Trial Outcomes & Findings for EMD 525797 in Colorectal and Ovarian Cancer Patients With Liver Metastases (NCT NCT00848510)

Last Updated: 2015-12-14

Results Overview

Toxicity was graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. A DLT was defined as any Grade 3 or 4 haematological or non-haematological toxicity occurring during the first 4 weeks of treatment (that is, until the beginning of Week 5, with the exception of Grade 3 asymptomatic increase in liver function tests (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], and alkaline phosphatase \[ALP\]) returning to Baseline within 7 days.), at any dose level, for which a causal relationship to the investigative medicinal product could not be ruled out by the Investigator and/or the Sponsor.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

41 participants

Primary outcome timeframe

Up to Week 4

Results posted on

2015-12-14

Participant Flow

First/last participant (informed consent): Feb2009/Sep 2013. Study completion date: 28 Nov 2013. The study was conducted at 2 centers in United Kingdom and Spain.

Enrolled: 61 screened for eligibility; 20 excluded (mainly non-fulfillment of inclusion or exclusion criteria), 41 participants were enrolled into the study.

Participant milestones

Participant milestones
Measure	Abituzumab 250 mg Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 milligram (mg) at Weeks 1, 3 and 5. In case of clinical benefit (stable disease \[SD\], complete response \[CR\], or partial response \[PR\]) as assessed by the Response Evaluation Criteria in Solid Tumors version (RECIST) Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.
Overall Study STARTED	10	13	8	10
Overall Study COMPLETED	10	13	8	10
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

EMD 525797 in Colorectal and Ovarian Cancer Patients With Liver Metastases

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abituzumab 250 mg n=10 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg n=13 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg n=10 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Total n=41 Participants Total of all reporting groups
Age, Continuous	61.6 Years STANDARD_DEVIATION 11.13 • n=5 Participants	58.9 Years STANDARD_DEVIATION 9.94 • n=7 Participants	68.9 Years STANDARD_DEVIATION 10.68 • n=5 Participants	57.8 Years STANDARD_DEVIATION 16.58 • n=4 Participants	61.2 Years STANDARD_DEVIATION 12.48 • n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants	22 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	2 Participants n=4 Participants	19 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to Week 4

Population: Dose escalation analysis set included all subjects in the safety analysis set who experienced any DLT during the DLT observation period, regardless of the number of investigational medicinal product (IMP) administrations and subjects who received the IMP at Weeks 1, 3, and 5 for Cohort 1 and at Weeks 1 and 3 for all other cohorts.

Outcome measures

Outcome measures
Measure	Abituzumab 250 mg n=6 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg n=12 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg n=6 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg n=7 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.
Number of Subjects With Dose Limiting Toxicities (DLTs)	1 Subjects	1 Subjects	0 Subjects	2 Subjects

PRIMARY outcome

Timeframe: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1

Population: The DCE-MRI analysis set included all subjects who had at least one valid predose scan and at least one valid postdose (that is, after the infusion) scan.

Volume transfer coefficient was defined as the volume transfer coefficient of contrast agent across the capillary wall, reflecting endothelial permeability and blood flow. Volumetric transfer coefficient was measured by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI is a noninvasive quantitative method of investigating microvascular structure and function by tracking the pharmacokinetics of injected low molecular weight contrast agents as they pass through tumor vasculature.

Outcome measures

Outcome measures
Measure	Abituzumab 250 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg n=12 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg n=10 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.
Volume Transfer Coefficient of Contrast Agent Across the Capillary Walls Week 1 Day 2	0.227 min^-1 Standard Deviation 0.0869	0.175 min^-1 Standard Deviation 0.1048	0.180 min^-1 Standard Deviation 0.0769	0.136 min^-1 Standard Deviation 0.0676
Volume Transfer Coefficient of Contrast Agent Across the Capillary Walls Screening 2	0.253 min^-1 Standard Deviation 0.1219	0.177 min^-1 Standard Deviation 0.1450	0.176 min^-1 Standard Deviation 0.0851	0.137 min^-1 Standard Deviation 0.0602
Volume Transfer Coefficient of Contrast Agent Across the Capillary Walls Week 1 Day 5	0.227 min^-1 Standard Deviation 0.0934	0.165 min^-1 Standard Deviation 0.1154	0.171 min^-1 Standard Deviation 0.0665	0.132 min^-1 Standard Deviation 0.0723
Volume Transfer Coefficient of Contrast Agent Across the Capillary Walls Week 2 Day 1	0.209 min^-1 Standard Deviation 0.0992	0.171 min^-1 Standard Deviation 0.1039	0.194 min^-1 Standard Deviation 0.0938	0.156 min^-1 Standard Deviation 0.0687
Volume Transfer Coefficient of Contrast Agent Across the Capillary Walls Screening 1	0.233 min^-1 Standard Deviation 0.0817	0.214 min^-1 Standard Deviation 0.1385	0.221 min^-1 Standard Deviation 0.0991	0.141 min^-1 Standard Deviation 0.0650

PRIMARY outcome

Timeframe: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1

Population: The DCE-MRI analysis set included all subjects who had at least one valid predose scan and at least one valid postdose (that is, after the infusion) scan.

Blood plasma volume and extracellular/extravascular volume was measured using DCE-MRI.

Outcome measures

Outcome measures
Measure	Abituzumab 250 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg n=12 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg n=10 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.
Blood Plasma Volume and Extravascular/Extracellular Volume Blood Plasma Volume: Week 1 Day 2	0.019 milliliter Standard Deviation 0.0078	0.014 milliliter Standard Deviation 0.0090	0.015 milliliter Standard Deviation 0.0114	0.020 milliliter Standard Deviation 0.0191
Blood Plasma Volume and Extravascular/Extracellular Volume Blood Plasma Volume: Week 1 Day 5	0.026 milliliter Standard Deviation 0.0155	0.017 milliliter Standard Deviation 0.0080	0.013 milliliter Standard Deviation 0.0082	0.023 milliliter Standard Deviation 0.0252
Blood Plasma Volume and Extravascular/Extracellular Volume Blood Plasma Volume: Screening 1	0.024 milliliter Standard Deviation 0.0162	0.014 milliliter Standard Deviation 0.0071	0.020 milliliter Standard Deviation 0.0122	0.022 milliliter Standard Deviation 0.0183
Blood Plasma Volume and Extravascular/Extracellular Volume Blood Plasma Volume: Screening 2	0.024 milliliter Standard Deviation 0.0125	0.013 milliliter Standard Deviation 0.0060	0.020 milliliter Standard Deviation 0.0252	0.016 milliliter Standard Deviation 0.0092
Blood Plasma Volume and Extravascular/Extracellular Volume Blood Plasma Volume: Week 2 Day 1	0.028 milliliter Standard Deviation 0.0201	0.019 milliliter Standard Deviation 0.0087	0.019 milliliter Standard Deviation 0.0220	0.020 milliliter Standard Deviation 0.0164
Blood Plasma Volume and Extravascular/Extracellular Volume Extravascular Volume: Screening 1	0.319 milliliter Standard Deviation 0.0649	0.385 milliliter Standard Deviation 0.1246	0.345 milliliter Standard Deviation 0.1352	0.313 milliliter Standard Deviation 0.0993
Blood Plasma Volume and Extravascular/Extracellular Volume Extravascular Volume: Screening 2	0.302 milliliter Standard Deviation 0.0559	0.319 milliliter Standard Deviation 0.1007	0.307 milliliter Standard Deviation 0.0860	0.307 milliliter Standard Deviation 0.0808
Blood Plasma Volume and Extravascular/Extracellular Volume Extravascular Volume: Week 1 Day 2	0.283 milliliter Standard Deviation 0.0464	0.335 milliliter Standard Deviation 0.1202	0.330 milliliter Standard Deviation 0.0723	0.327 milliliter Standard Deviation 0.0714
Blood Plasma Volume and Extravascular/Extracellular Volume Extravascular Volume: Week 1 Day 5	0.271 milliliter Standard Deviation 0.0531	0.327 milliliter Standard Deviation 0.1162	0.336 milliliter Standard Deviation 0.1080	0.312 milliliter Standard Deviation 0.0924
Blood Plasma Volume and Extravascular/Extracellular Volume Extravascular Volume: Week 2 Day 1	0.286 milliliter Standard Deviation 0.0700	0.316 milliliter Standard Deviation 0.1125	0.345 milliliter Standard Deviation 0.0803	0.297 milliliter Standard Deviation 0.0636

PRIMARY outcome

Timeframe: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1

Population: The DCE-MRI analysis set included all subjects who had at least one valid predose scan and at least one valid postdose (that is, after the infusion) scan.

IAUC 60 was used to give a gross indication of the delivery and uptake of contrast agent within the tumor (indicating the degree of perfusion and endothelial permeability. IAUC60 was measured using DCE-MRI.

Outcome measures

Outcome measures
Measure	Abituzumab 250 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg n=12 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg n=10 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.
Initial Area Under the DCE-MRI Contrast Agent Concentration Time Curve After 60 Seconds (IAUC60) Screening 1	21.900 (Millimoles/liter)*sec Standard Deviation 6.0987	20.844 (Millimoles/liter)*sec Standard Deviation 8.8439	22.752 (Millimoles/liter)*sec Standard Deviation 8.2156	16.602 (Millimoles/liter)*sec Standard Deviation 7.9627
Initial Area Under the DCE-MRI Contrast Agent Concentration Time Curve After 60 Seconds (IAUC60) Screening 2	21.155 (Millimoles/liter)*sec Standard Deviation 6.4053	17.670 (Millimoles/liter)*sec Standard Deviation 9.0159	19.437 (Millimoles/liter)*sec Standard Deviation 8.5201	16.168 (Millimoles/liter)*sec Standard Deviation 6.9961
Initial Area Under the DCE-MRI Contrast Agent Concentration Time Curve After 60 Seconds (IAUC60) Week 1 Day 2	22.513 (Millimoles/liter)*sec Standard Deviation 6.8728	18.140 (Millimoles/liter)*sec Standard Deviation 8.1305	18.724 (Millimoles/liter)*sec Standard Deviation 6.6599	17.607 (Millimoles/liter)*sec Standard Deviation 9.2052
Initial Area Under the DCE-MRI Contrast Agent Concentration Time Curve After 60 Seconds (IAUC60) Week 1 Day 5	21.006 (Millimoles/liter)*sec Standard Deviation 5.7951	17.557 (Millimoles/liter)*sec Standard Deviation 9.9606	18.758 (Millimoles/liter)*sec Standard Deviation 5.1517	16.313 (Millimoles/liter)*sec Standard Deviation 9.0325
Initial Area Under the DCE-MRI Contrast Agent Concentration Time Curve After 60 Seconds (IAUC60) Week 2 Day 1	20.356 (Millimoles/liter)*sec Standard Deviation 6.6613	18.498 (Millimoles/liter)*sec Standard Deviation 8.4957	20.201 (Millimoles/liter)*sec Standard Deviation 7.1768	17.314 (Millimoles/liter)*sec Standard Deviation 7.5539

PRIMARY outcome

Timeframe: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1

Population: The DCE-MRI analysis set included all subjects who had at least one valid predose scan and at least one valid postdose (that is, after the infusion) scan.

Tumor volume (three-dimensional measurement) and the enhancing fraction of the tumor, which provides a gross measure of the proportion of the tumor that has a measurable level of perfusion, were assessed using DCE-MRI.

Outcome measures

Outcome measures
Measure	Abituzumab 250 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg n=12 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg n=10 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.
Whole Tumor Volume and Enhancing Tumor Volume Whole Tumor Volume: Screening 1	180310.380 Cubic millimeter (mm^3) Standard Deviation 254443.5241	83921.304 Cubic millimeter (mm^3) Standard Deviation 85983.0790	58662.341 Cubic millimeter (mm^3) Standard Deviation 49075.1555	58665.247 Cubic millimeter (mm^3) Standard Deviation 101041.3892
Whole Tumor Volume and Enhancing Tumor Volume Whole tumor volume: Screening 2	195939.314 Cubic millimeter (mm^3) Standard Deviation 268158.6384	73940.030 Cubic millimeter (mm^3) Standard Deviation 81243.6227	57573.776 Cubic millimeter (mm^3) Standard Deviation 48175.9173	63694.678 Cubic millimeter (mm^3) Standard Deviation 121709.7593
Whole Tumor Volume and Enhancing Tumor Volume Whole tumor volume: Week 1 Day 2	188556.463 Cubic millimeter (mm^3) Standard Deviation 260719.8741	76214.685 Cubic millimeter (mm^3) Standard Deviation 84401.6466	62941.056 Cubic millimeter (mm^3) Standard Deviation 56871.6273	68159.203 Cubic millimeter (mm^3) Standard Deviation 122487.7558
Whole Tumor Volume and Enhancing Tumor Volume Whole tumor volume: Week 1 Day 5	195172.560 Cubic millimeter (mm^3) Standard Deviation 264976.6619	72302.778 Cubic millimeter (mm^3) Standard Deviation 79746.9479	68160.675 Cubic millimeter (mm^3) Standard Deviation 61512.3298	74122.030 Cubic millimeter (mm^3) Standard Deviation 135359.3601
Whole Tumor Volume and Enhancing Tumor Volume Whole tumor volume: Week 2 Day 1	200316.632 Cubic millimeter (mm^3) Standard Deviation 271342.9822	84412.235 Cubic millimeter (mm^3) Standard Deviation 95360.1124	76755.877 Cubic millimeter (mm^3) Standard Deviation 75170.5945	75468.633 Cubic millimeter (mm^3) Standard Deviation 142025.4967
Whole Tumor Volume and Enhancing Tumor Volume EnhancingTumor Volume: Screening 1	173882.006 Cubic millimeter (mm^3) Standard Deviation 243514.1367	71043.485 Cubic millimeter (mm^3) Standard Deviation 73510.7915	58160.983 Cubic millimeter (mm^3) Standard Deviation 49084.1307	32790.886 Cubic millimeter (mm^3) Standard Deviation 17602.3758
Whole Tumor Volume and Enhancing Tumor Volume Enhancing tumor volume: Screening 2	190189.883 Cubic millimeter (mm^3) Standard Deviation 259044.1496	70835.730 Cubic millimeter (mm^3) Standard Deviation 75748.1887	56818.305 Cubic millimeter (mm^3) Standard Deviation 48373.6133	68940.184 Cubic millimeter (mm^3) Standard Deviation 118913.2150
Whole Tumor Volume and Enhancing Tumor Volume Enhancing tumor volume: Week 1 Day 2	184552.465 Cubic millimeter (mm^3) Standard Deviation 254423.3623	71323.352 Cubic millimeter (mm^3) Standard Deviation 76071.6880	61519.396 Cubic millimeter (mm^3) Standard Deviation 55375.5040	70147.221 Cubic millimeter (mm^3) Standard Deviation 117332.7409
Whole Tumor Volume and Enhancing Tumor Volume Enhancing tumor volume: Week 1 Day 5	189836.185 Cubic millimeter (mm^3) Standard Deviation 256862.4972	71293.696 Cubic millimeter (mm^3) Standard Deviation 75853.1409	66927.883 Cubic millimeter (mm^3) Standard Deviation 61671.2327	74973.916 Cubic millimeter (mm^3) Standard Deviation 133033.3585
Whole Tumor Volume and Enhancing Tumor Volume Enhancing tumor volume: Week 2 Day 1	206074.402 Cubic millimeter (mm^3) Standard Deviation 270622.8624	83616.930 Cubic millimeter (mm^3) Standard Deviation 92140.5994	75835.576 Cubic millimeter (mm^3) Standard Deviation 75420.1670	41201.278 Cubic millimeter (mm^3) Standard Deviation 25012.0230

SECONDARY outcome

Timeframe: From the initiation of the trial treatment until 30 days after last administration of trial treatment.

Population: The safety analysis set included all subjects who received at least one dose of IMP administration.

An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/ significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were the AEs that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	Abituzumab 250 mg n=10 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg n=13 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg n=10 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death TEAEs	10 Subjects	13 Subjects	8 Subjects	10 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death Serious TEAEs	5 Subjects	7 Subjects	5 Subjects	7 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death TEAEs leading to Discontinuation	1 Subjects	2 Subjects	1 Subjects	2 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death TEAEs Leading to Death	0 Subjects	1 Subjects	2 Subjects	1 Subjects

SECONDARY outcome

Timeframe: Up to 4 years

Population: The full analysis set included all subjects who received at least one dose of IMP administration. "N" signifies the total number of participants evaluable for this outcome measure. Same subjects may be reported in more than one category.

Tumor response was assessed by the Investigator, based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 criteria. Tumor response was defined as the presence of a "best overall response" of complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions and/or normalization of serum levels of tumor markers. PR: At least a 30 percent decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD of target lesions. The qualification of a CR or of a PR needed a confirmation by a second computed tomography (CT) scan at least 4 weeks after the first scan. Best overall response was derived programmatically as the best response recorded from the first investigation medicinal product administration until disease progression. Clinical benefit was defined as the presence of a "best overall response" of complete response or partial response or stable disease lasting at least 6 weeks.

Outcome measures

Outcome measures
Measure	Abituzumab 250 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg n=11 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg n=7 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg n=6 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.
Number of Subjects With Best Overall Response, Tumor Response and Clinical Benefit CR	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Best Overall Response, Tumor Response and Clinical Benefit PR	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Best Overall Response, Tumor Response and Clinical Benefit SD	0 Subjects	2 Subjects	1 Subjects	0 Subjects
Number of Subjects With Best Overall Response, Tumor Response and Clinical Benefit Progressive Disease	8 Subjects	9 Subjects	6 Subjects	5 Subjects
Number of Subjects With Best Overall Response, Tumor Response and Clinical Benefit Not Assessable	0 Subjects	0 Subjects	0 Subjects	1 Subjects
Number of Subjects With Best Overall Response, Tumor Response and Clinical Benefit Tumor Response	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Best Overall Response, Tumor Response and Clinical Benefit Clinical Benefit	0 Subjects	2 Subjects	1 Subjects	0 Subjects

SECONDARY outcome

Timeframe: Up to 4 weeks after last dose administration

Population: The safety analysis set included all subjects who received at least one dose of IMP administration.

The number of subjects who experienced worse post baseline shift were assessed as per ECOG performance status score recorded during the treatment. The ECOG score is categorized as Grade 0, 1, 2, 3 and 4 where Grade 0=fully active, Grade 1=restricted in physically strenuous activity, Grade 2=unable to carry out any work activities, Grade 3=capable of only limited self-care and Grade 4=completely disabled.

Outcome measures

Outcome measures
Measure	Abituzumab 250 mg n=10 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg n=13 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg n=10 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.
Number of Subjects With Worsened Post Baseline Shift in ECOG Performance Status Score	4 Subjects	8 Subjects	4 Subjects	5 Subjects

SECONDARY outcome

Timeframe: Day 1 of Weeks 1, 3, 5, 6, 7, 8, and week 11 and end of study (EOS) visit (4 weeks after last dose administration)

Population: The immunogenicity analysis set included all subjects who received at least one dose of study drug administration and provided sufficient data from the antibodies samples. 'N' (number of subjects analyzed) signifies the subjects evaluable for this outcome measure. "n" signifies the number of subjects evaluable for each time point, respectively.

Subjects were defined as abituzumab positive if at least one positive result of antibodies against abituzumab was observed. In all other cases, subjects were defined as abituzumab negative.

Outcome measures

Outcome measures
Measure	Abituzumab 250 mg n=9 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg n=11 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg n=7 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg n=7 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.
Number of Subjects With Positive Binding Abituzumab Antibodies Week 1 Day 1 (n=9,11,7,7)	0 Subjects	1 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Binding Abituzumab Antibodies Week 3 Day 1 (n=9,11,7,7)	1 Subjects	0 Subjects	2 Subjects	0 Subjects
Number of Subjects With Positive Binding Abituzumab Antibodies Week 5 Day 1 (n=6,9,6,2)	0 Subjects	1 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Binding Abituzumab Antibodies Week 6 Day 1 (n=0,6,5,2)	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Binding Abituzumab Antibodies Week 7 Day 1 (n=0,5,5,2)	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Binding Abituzumab Antibodies Week 8 Day 1 (n=4,0,0,0)	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Binding Abituzumab Antibodies Week 11 (n=0,1,3,0)	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Positive Binding Abituzumab Antibodies EOS Visit (n=6,3,2,1)	1 Subjects	0 Subjects	0 Subjects	0 Subjects

SECONDARY outcome

Timeframe: Time from first study drug intake to disease progression, death or last tumor assessment until end of trial visit (4 weeks after last dose administration)

Population: The safety analysis set included all subjects who received at least one dose of IMP administration.

PFS was defined as the time from first study drug intake until radiological progression (based on RECIST Version 1.0) or death due to any cause. Only deaths within 84 days of last tumor assessment are considered. Subjects without event were censored on the date of last tumor assessment. Investigator read was the assessment of all imaging by the treating physician at the local trial site.

Outcome measures

Outcome measures
Measure	Abituzumab 250 mg n=10 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg n=13 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg n=8 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg n=10 Participants Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.
Progression-Free Survival (PFS) Time	1.22 months Interval 0.0 to 1.3	0.77 months Interval 0.0 to 7.6	1.40 months Interval 1.0 to 10.7	1.08 months Interval 0.0 to 1.2

Adverse Events

Abituzumab 250 mg

Serious events: 5 serious events

Other events: 10 other events

Deaths: 0 deaths

Abituzumab 500 mg

Serious events: 7 serious events

Other events: 13 other events

Deaths: 0 deaths

Abituzumab 1000 mg

Serious events: 5 serious events

Other events: 8 other events

Deaths: 0 deaths

Abituzumab 1500 mg

Serious events: 7 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Merck KGaA Communication Center

Merck Serono, a division of Merck KGaA

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Abituzumab 250 mg n=10 participants at risk Abituzumab was administered as an intravenous infusion for an hour at a dose of 250 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 500 mg n=13 participants at risk Abituzumab was administered as an intravenous infusion for an hour at a dose of 500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1000 mg n=8 participants at risk Abituzumab was administered as an intravenous infusion for an hour at a dose of 1000 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.	Abituzumab 1500 mg n=10 participants at risk Abituzumab was administered as an intravenous infusion for an hour at a dose of 1500 mg at Weeks 1, 3 and 5. In case of clinical benefit (SD, CR, or PR) as assessed by the RECIST Version 1.0 during initial 6 Weeks, subjects were allowed to continue treatment at the start of Week 7 at the given dose every second week until intolerance to treatment, withdrawal of consent, or the subject was no longer benefiting from treatment in the opinion of the Investigator.
Cardiac disorders Myocardial ischaemia	10.0% 1/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	7.7% 1/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	10.0% 1/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Gastrointestinal disorders Abdominal pain upper	10.0% 1/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	10.0% 1/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Gastrointestinal disorders Ascites	20.0% 2/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Gastrointestinal disorders Constipation	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	10.0% 1/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	12.5% 1/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
General disorders Pyrexia	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	12.5% 1/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	30.0% 3/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
General disorders Asthenia	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	7.7% 1/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	10.0% 1/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
General disorders Disease progression	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	10.0% 1/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	15.4% 2/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Hepatobiliary disorders Cholangitis	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	10.0% 1/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Hepatobiliary disorders Hepatic failure	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	12.5% 1/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Immune system disorders Drug hypersensitivity	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	20.0% 2/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Infections and infestations Biliary tract infection	10.0% 1/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Investigations International normalised ratio increased	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	7.7% 1/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Metabolism and nutrition disorders Dehydration	10.0% 1/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	12.5% 1/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	10.0% 1/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	10.0% 1/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Nervous system disorders Haemorrhage intracranial	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	7.7% 1/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Nervous system disorders Hemiparesis	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	7.7% 1/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	12.5% 1/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.
Infections and infestations Hepatobiliary infection	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	7.7% 1/13 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/8 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.	0.00% 0/10 • From the initiation of the trial treatment until 30 days after last administration of trial treatment.