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Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT02709889
Recruitment Status : Terminated (Strategic considerations)
First Posted : March 16, 2016
Results First Posted : October 19, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Malignant Melanoma
Medullary Thyroid Cancer
Glioblastoma
Large-Cell Neuroendocrine Carcinoma
Neuroendocrine Prostate Cancer
High Grade Gastroenteropancreatic Neuroendocrine Carcinoma
Other Neuroendocrine Carcinoma
Other Solid Tumors
Interventions Drug: Rovalpituzumab tesirine
Drug: Dexamethasone
Enrollment 200
Recruitment Details  
Pre-assignment Details Participants were enrolled into a standard 3+3 dose-escalation study within disease-specific cohorts in Part A, and then participants were enrolled into a disease-specific expansion cohort in Part B based on the maximum tolerated dose determined in Part A.
Arm/Group Title Part A: Rovalpituzumab Tesirine 0.2 mg/kg Part A: Rovalpituzumab Tesirine 0.3 mg/kg Part A: Rovalpituzumab Tesirine 0.4 mg/kg Part B: Rovalpituzumab Tesirine 0.3 mg/kg
Hide Arm/Group Description Participants who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants who received rovalpituzumab tesirine 0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Period Title: Overall Study
Started 43 57 12 88
Large Cell Neuroendocrine Carcinoma(NEC) 3 4 2 4
Neuroendocrine Prostate Cancer 4 7 3 7
Gastroenteropancreatic NEC 6 5 2 23
Other NEC 11 12 1 7
Malignant Melanoma 3 6 0 11
Medullary Thyroid Cancer 3 3 0 7
Glioblastoma 4 4 1 14
Other Solid Tumors 9 16 3 15
Completed 0 0 0 0
Not Completed 43 57 12 88
Reason Not Completed
Withdrawal by Subject             11             10             2             12
Death             25             38             4             44
Physician Decision             1             2             3             5
Lost to Follow-up             2             0             0             4
Study Terminated by Sponsor             4             6             2             17
Other, Not Specified             0             1             1             6
Arm/Group Title Large Cell Neuroendocrine Carcinoma Neuroendocrine Prostate Cancer Gastroenteropancreatic Neuroendocrine Carcinoma Other Neuroendocrine Carcinoma Malignant Melanoma Medullary Thyroid Cancer Glioblastoma Other Solid Tumors Total
Hide Arm/Group Description Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with neuroendocrine prostate cancer (NEPC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with malignant melanoma (MM) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with medullary thyroid cancer (MTC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with glioblastoma (GBM) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with other solid tumors who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Total of all reporting groups
Overall Number of Baseline Participants 13 21 36 31 20 13 23 43 200
Hide Baseline Analysis Population Description
Baseline characteristics are presented by disease-specific cohorts, inclusive of participants in parts A and B.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 21 participants 36 participants 31 participants 20 participants 13 participants 23 participants 43 participants 200 participants
< 65 years old
7
  53.8%
7
  33.3%
25
  69.4%
19
  61.3%
11
  55.0%
11
  84.6%
17
  73.9%
23
  53.5%
120
  60.0%
>= 65 years old
6
  46.2%
14
  66.7%
11
  30.6%
12
  38.7%
9
  45.0%
2
  15.4%
6
  26.1%
20
  46.5%
80
  40.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 21 participants 36 participants 31 participants 20 participants 13 participants 23 participants 43 participants 200 participants
Female
5
  38.5%
0
   0.0%
13
  36.1%
17
  54.8%
10
  50.0%
5
  38.5%
4
  17.4%
20
  46.5%
74
  37.0%
Male
8
  61.5%
21
 100.0%
23
  63.9%
14
  45.2%
10
  50.0%
8
  61.5%
19
  82.6%
23
  53.5%
126
  63.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 21 participants 36 participants 31 participants 20 participants 13 participants 23 participants 43 participants 200 participants
White
11
  84.6%
17
  81.0%
32
  88.9%
25
  80.6%
20
 100.0%
10
  76.9%
20
  87.0%
40
  93.0%
175
  87.5%
Black or African American
0
   0.0%
3
  14.3%
3
   8.3%
2
   6.5%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.3%
9
   4.5%
Asian
2
  15.4%
0
   0.0%
1
   2.8%
2
   6.5%
0
   0.0%
1
   7.7%
1
   4.3%
0
   0.0%
7
   3.5%
Other, Not Specified
0
   0.0%
1
   4.8%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
0
   0.0%
1
   2.3%
3
   1.5%
Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
2
   6.5%
0
   0.0%
1
   7.7%
2
   8.7%
1
   2.3%
6
   3.0%
1.Primary Outcome
Title Summary of Treatment-Emergent Adverse Events (TEAEs), by Dose and Neuroendocrine (NEC) or Non-NEC Disease Groups
Hide Description The number of participants with TEAEs, serious TEAEs, study drug-related TEAEs, and study drug discontinuations or dose reductions due to TEAEs, summarized by dose received and neuroendocrine (NEC) or non-NEC disease groups. An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that at any dose: is fatal or life-threatening; results in death or hospitalization; is disabling/incapacitating or a congenital anomaly/birth defect; is medically significant. AE severity was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03 terminology: grade 1=mild; grade 2=moderate; grade 3=severe; grade 4 life-threatening; grade 5=death. TEAEs were defined as AEs that were newly occurring or worsened following study treatment.
Time Frame From first dose of study drug through 30 days after last dose. The overall mean number of 6-week treatment cycles was 1 (range 1.0, 5.0).
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: participants who received any amount of study drug. Presented by NEC/Non-NEC groups, inclusive of participants in parts A and B.
Arm/Group Title NEC: 0.2 mg/kg NEC: 0.3 mg/kg NEC: 0.4 mg/kg NEC: Any Dose Non-NEC: 0.2 mg/kg Non-NEC: 0.3 mg/kg Non-NEC: 0.4 mg/kg Non-NEC: Any Dose
Hide Arm/Group Description:
Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin, neuroendocrine prostate cancer (NEPC), high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC), other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin, neuroendocrine prostate cancer (NEPC), high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC), other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin, neuroendocrine prostate cancer (NEPC), high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC), other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received rovalpituzumab tesirine 0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin, neuroendocrine prostate cancer (NEPC), high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC), other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with malignant melanoma (MM), medullary thyroid cancer (MTC), glioblastoma (GBM), or other solid tumors who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with malignant melanoma (MM), medullary thyroid cancer (MTC), glioblastoma (GBM), or other solid tumors who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with malignant melanoma (MM), medullary thyroid cancer (MTC), glioblastoma (GBM), or other solid tumors who received rovalpituzumab tesirine 0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with malignant melanoma (MM), medullary thyroid cancer (MTC), glioblastoma (GBM), or other solid tumors who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Overall Number of Participants Analyzed 24 69 8 101 19 76 4 99
Measure Type: Number
Unit of Measure: participants
≥ 1 TEAE 24 69 8 101 18 75 4 97
≥ 1 TEAE, Grade 3-4 20 40 5 65 10 38 4 52
≥ 1 TEAE, Grade 5 1 13 2 16 3 8 0 11
≥ 1 Serious TEAE 16 39 5 60 10 38 3 51
≥ 1 Serious TEAE, Grade 3-4 16 24 3 43 6 25 3 34
≥ 1 Serious TEAE, Grade 5 0 13 2 15 3 8 0 11
≥ 1 Drug-Related (DR) Serious TEAE 6 20 3 29 3 14 3 20
≥ 1 DR Serious TEAE, Grade 3-4 6 15 1 22 3 8 3 14
≥ 1 DR Serious TEAE, Grade 5 0 2 2 4 0 2 0 2
≥ 1 DR TEAE 21 64 8 93 16 68 4 88
≥ 1 DR TEAE, Grade 3-4 14 43 3 60 6 27 4 37
≥ 1 DR TEAE, Grade 5 0 2 2 4 0 2 0 2
≥1 TEAE Leading to Study Drug Discontinuation (DC) 4 15 5 24 5 10 2 14
≥ 1 TEAE Leading to Study Drug DC, Grade 3-4 2 11 2 15 4 4 2 8
≥1 TEAE Leading to Study Drug DC, Grade 5 0 1 2 3 1 2 0 2
≥ 1 DR TEAE Leading to Study Drug DC 4 10 4 18 2 10 2 14
≥ 1 DR TEAE Leading to Study Drug DC, Grade 3-4 2 7 1 10 2 4 2 8
≥ 1 DR TEAE Leading to Study Drug DC, Grade 5 0 1 2 3 0 2 0 2
≥ 1 TEAE Leading to Dose Reduction 0 7 2 9 0 7 0 7
≥ 1 TEAE Leading to Dose Reduction, Grade 3-4 0 5 1 6 0 4 0 4
≥ 1 TEAE Leading to Dose Reduction, Grade 5 0 0 0 0 0 0 0 0
2.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR is defined as percentage of participants whose best overall response was either complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: A ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All enrolled participants who received any amount of study drug. Presented by disease-specific groups, inclusive of participants in parts A and B.
Arm/Group Title Large Cell Neuroendocrine Carcinoma Neuroendocrine Prostate Cancer Gastroenteropancreatic Neuroendocrine Carcinoma Other Neuroendocrine Carcinoma Malignant Melanoma Medullary Thyroid Cancer Glioblastoma Other Solid Tumors
Hide Arm/Group Description:
Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with neuroendocrine prostate cancer (NEPC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with malignant melanoma (MM) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with medullary thyroid cancer (MTC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with glioblastoma (GBM) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with other solid tumors who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Overall Number of Participants Analyzed 13 21 36 31 20 13 23 43
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
7.7
(0.2 to 36.0)
4.8
(0.1 to 23.8)
13.9
(4.7 to 29.5)
22.6
(9.6 to 41.1)
10.0
(1.2 to 31.7)
15.4
(1.9 to 45.4)
4.3
(0.1 to 21.9)
4.7
(0.6 to 15.8)
3.Secondary Outcome
Title Clinical Benefit Rate (CBR)
Hide Description CBR is defined as the percentage of participants with best overall response (confirmed or unconfirmed) of CR, PR or stable disease (SD) per RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: A ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressed disease (PD), taking as reference the smallest sum diameters while on study. SD criteria must have met at least once after study entry at a minimum interval of 42 days (-7 days to allow for scheduled visit window per the protocol).
Time Frame Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All enrolled participants who received any amount of study drug. Presented by disease-specific groups, inclusive of participants in parts A and B.
Arm/Group Title Large Cell Neuroendocrine Carcinoma Neuroendocrine Prostate Cancer Gastroenteropancreatic Neuroendocrine Carcinoma Other Neuroendocrine Carcinoma Malignant Melanoma Medullary Thyroid Cancer Glioblastoma Other Solid Tumors
Hide Arm/Group Description:
Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with neuroendocrine prostate cancer (NEPC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with malignant melanoma (MM) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with medullary thyroid cancer (MTC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with glioblastoma (GBM) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with other solid tumors who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Overall Number of Participants Analyzed 13 21 36 31 20 13 23 43
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
76.9
(46.2 to 95.0)
76.2
(52.8 to 91.8)
63.9
(46.2 to 79.2)
61.3
(42.2 to 78.2)
60.0
(36.1 to 80.9)
76.9
(46.2 to 95.0)
30.4
(13.2 to 52.9)
46.5
(31.2 to 62.3)
4.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR is defined as the time from the first assessment on therapy of a CR or PR response (per RECIST v1.1) to the date of progressive disease or death. CR: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: A ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not have progression were censored at the last non-missing response assessment on-therapy or baseline. Based on Kaplan-Meier estimates.
Time Frame Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All enrolled participants who received any amount of study drug. Responders (CR or PR response). Presented by disease-specific groups, inclusive of participants in parts A and B.
Arm/Group Title Large Cell Neuroendocrine Carcinoma Neuroendocrine Prostate Cancer Gastroenteropancreatic Neuroendocrine Carcinoma Other Neuroendocrine Carcinoma Malignant Melanoma Medullary Thyroid Cancer Glioblastoma Other Solid Tumors
Hide Arm/Group Description:
Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with neuroendocrine prostate cancer (NEPC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with malignant melanoma (MM) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with medullary thyroid cancer (MTC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with glioblastoma (GBM) who received rovalpituzumab rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with other solid tumors who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Overall Number of Participants Analyzed 2 4 9 8 3 2 1 3
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
3.0
(2.8 to 3.1)
2.6
(0.5 to 3.7)
6.7 [1] 
(2.0 to NA)
NA [1] 
(2.9 to NA)
NA [1] 
(4.5 to NA)
4.6 [2] 
(NA to NA)
3.9
(0.4 to 4.1)
[1]
NA=Not Estimable. Statistic could not be estimated due to an insufficient number of participants with progressive disease.
[2]
1 participant analyzed
5.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS is defined as the time from the first dose date to the date of disease progression or death. Participants who did not have progression or death are censored at the last non-missing response assessment on-therapy or baseline. Based on Kaplan-Meier estimates.
Time Frame Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
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Hide Analysis Population Description
Full Analysis Set: All enrolled participants who received any amount of study drug. Presented by disease-specific groups, inclusive of participants in parts A and B.
Arm/Group Title Large Cell Neuroendocrine Carcinoma Neuroendocrine Prostate Cancer Gastroenteropancreatic Neuroendocrine Carcinoma Other Neuroendocrine Carcinoma Malignant Melanoma Medullary Thyroid Cancer Glioblastoma Other Solid Tumors
Hide Arm/Group Description:
Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with neuroendocrine prostate cancer (NEPC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with malignant melanoma (MM) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with medullary thyroid cancer (MTC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with glioblastoma (GBM) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with other solid tumors who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Overall Number of Participants Analyzed 13 21 36 31 20 13 23 43
Median (95% Confidence Interval)
Unit of Measure: months
4.6 [1] 
(1.2 to NA)
4.5
(2.5 to 5.7)
3.3
(2.3 to 5.0)
3.1
(1.3 to 6.0)
2.9
(1.3 to 3.7)
11.7 [1] 
(1.3 to NA)
1.4
(1.3 to 2.5)
2.1
(1.3 to 3.3)
[1]
NA=Not Estimable. Statistic could not be estimated due to an insufficient number of participants with progressive disease.
6.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival is defined as the time from the first dose date to death for any reason. Subjects who were alive at the clinical data cut-off are censored at the last known alive date. Based on Kaplan-Meier estimates.
Time Frame Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: All enrolled participants who received any amount of study drug. Presented by disease-specific groups, inclusive of participants in parts A and B.
Arm/Group Title Large Cell Neuroendocrine Carcinoma Neuroendocrine Prostate Cancer Gastroenteropancreatic Neuroendocrine Carcinoma Other Neuroendocrine Carcinoma Malignant Melanoma Medullary Thyroid Cancer Glioblastoma Other Solid Tumors
Hide Arm/Group Description:
Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with neuroendocrine prostate cancer (NEPC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with malignant melanoma (MM) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with medullary thyroid cancer (MTC) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with glioblastoma (GBM) who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants with other solid tumors who received rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Overall Number of Participants Analyzed 13 21 36 31 20 13 23 43
Median (95% Confidence Interval)
Unit of Measure: months
7.7 [1] 
(2.4 to NA)
5.7
(2.7 to 7.3)
6.7
(3.9 to 9.7)
6.6
(4.3 to 12.2)
7.5
(3.6 to 9.2)
NA [1] 
(6.0 to NA)
6.6
(3.7 to 7.4)
5.5
(4.2 to 6.0)
[1]
NA=Not Estimable. Statistic could not be estimated due to an insufficient number of participants with progressive disease.
7.Secondary Outcome
Title Serum Concentrations of Rovalpituzumab Tesirine Over Time
Hide Description [Not Specified]
Time Frame Cycle 1: 0, 0.5, 6, 48, 168, 336, 672 hours postdose
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Hide Analysis Population Description
Participants who received at least 1 dose of study drug and had an assessment at given time point. Presented by dose-specific groups, inclusive of participants in parts A and B.
Arm/Group Title 0.2 mg/kg 0.3 mg/kg 0.4 mg/kg
Hide Arm/Group Description:
Participants who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants who received rovalpituzumab tesirine 0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Overall Number of Participants Analyzed 43 139 12
Mean (Standard Deviation)
Unit of Measure: ug/mL
Cycle 1: 0 hour Number Analyzed 42 participants 138 participants 12 participants
0.057  (0.367) 0.044  (0.507) 0  (0)
Cycle 1: 0.5 hour postdose Number Analyzed 42 participants 139 participants 12 participants
4.799  (1.474) 7.351  (2.640) 10.785  (1.516)
Cycle 1: 6 hours postdose Number Analyzed 43 participants 128 participants 11 participants
4.377  (1.222) 6.710  (1.701) 9.355  (0.859)
Cycle 1: 48 hours postdose Number Analyzed 43 participants 135 participants 11 participants
2.760  (0.939) 4.483  (1.317) 6.049  (1.171)
Cycle 1: 168 hours postdose Number Analyzed 40 participants 131 participants 12 participants
1.494  (0.569) 2.392  (0.902) 3.250  (0.825)
Cycle 1: 336 hours postdose Number Analyzed 41 participants 124 participants 12 participants
0.963  (0.470) 1.633  (0.710) 2.302  (0.703)
Cycle 1: 672 hours postdose Number Analyzed 40 participants 116 participants 8 participants
0.515  (0.278) 0.976  (0.410) 1.272  (0.414)
8.Secondary Outcome
Title Number of Participants With Anti-therapeutic Antibodies (ATA)
Hide Description Number of participants treated across each dose level reported to potentially have ATAs against rovalpituzumab tesirine at any time during the study.
Time Frame Day 1 and 42 days after last dose. The overall mean number of 6-week treatment cycles was 1 (range 1.0, 5.0).
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Hide Analysis Population Description
Participants who received at least 1 dose of study drug with available ATA data. Presented by dose-specific groups, inclusive of participants in parts A and B.
Arm/Group Title 0.2 mg/kg 0.3 mg/kg 0.4 mg/kg
Hide Arm/Group Description:
Participants who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Participants who received rovalpituzumab tesirine 0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Overall Number of Participants Analyzed 42 145 12
Measure Type: Number
Unit of Measure: participants
5 10 1
Time Frame From first dose of study drug through 30 days after last dose. The overall mean number of 6-week treatment cycles was 1 (range 1.0, 5.0).
Adverse Event Reporting Description No participants with malignant melanoma (MM) or medullary thyroid cancer (MTC) received the rovalpituzumab tesirine 0.4 mg/kg dose.
 
Arm/Group Title 0.2_mg_kg_(LCNEC) 0.2_mg_kg_(NEPC) 0.2_mg_kg_(GEPNEC) 0.2_mg_kg_(Other_NEC) 0.2_mg_kg_(MM) 0.2_mg_kg_(MTC) 0.2_mg_kg_(GBM) 0.2_mg_kg_(Other_Solid) 0.3_mg_kg_(LCNEC) 0.3_mg_kg_(NEPC) 0.3_mg_kg_(GEPNEC) 0.3_mg_kg_(Other_NEC) 0.3_mg_kg_(MM) 0.3_mg_kg_(MTC) 0.3_mg_kg_(GBM) 0.3_mg_kg_(Other_Solid) 0.4_mg_kg_(GBM) 0.4_mg_kg_(GEPNEC) 0.4_mg_kg_(LCNEC) 0.4_mg_kg_(NEPC) 0.4_mg_kg_(Other_NEC) 0.4_mg_kg_(Other_Solid)
Hide Arm/Group Description Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with neuroendocrine prostate cancer (NEPC) who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.

Participants with high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC) who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle.

Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.

Participants with other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with malignant melanoma (MM) who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with medullary thyroid cancer (MTC) who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with glioblastoma (GBM) who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with other solid tumors who received rovalpituzumab tesirine 0.2 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with neuroendocrine prostate cancer (NEPC) who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.

Participants with high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC) who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle.

Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.

Participants with other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with malignant melanoma (MM) who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with medullary thyroid cancer (MTC) who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with glioblastoma (GBM) who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with other solid tumors who received rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with glioblastoma (GBM) who received rovalpituzumab tesirine 0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.

Participants with high-grade gastroenteropancreatic neuroendocrine carcinoma (GEP NEC) who received rovalpituzumab tesirine 0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle.

Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.

Participants with large cell neuroendocrine carcinoma (LCNEC) of any origin who received rovalpituzumab tesirine 0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with neuroendocrine prostate cancer (NEPC) who received rovalpituzumab tesirine 0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with other neuroendocrine carcinoma (NEC), and high-grade neuroendocrine tumors who received rovalpituzumab tesirine 0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle. Participants with other solid tumors who received rovalpituzumab tesirine 0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
All-Cause Mortality
0.2_mg_kg_(LCNEC) 0.2_mg_kg_(NEPC) 0.2_mg_kg_(GEPNEC) 0.2_mg_kg_(Other_NEC) 0.2_mg_kg_(MM) 0.2_mg_kg_(MTC) 0.2_mg_kg_(GBM) 0.2_mg_kg_(Other_Solid) 0.3_mg_kg_(LCNEC) 0.3_mg_kg_(NEPC) 0.3_mg_kg_(GEPNEC) 0.3_mg_kg_(Other_NEC) 0.3_mg_kg_(MM) 0.3_mg_kg_(MTC) 0.3_mg_kg_(GBM) 0.3_mg_kg_(Other_Solid) 0.4_mg_kg_(GBM) 0.4_mg_kg_(GEPNEC) 0.4_mg_kg_(LCNEC) 0.4_mg_kg_(NEPC) 0.4_mg_kg_(Other_NEC) 0.4_mg_kg_(Other_Solid)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/3 (33.33%)      3/4 (75.00%)      5/6 (83.33%)      9/11 (81.82%)      3/3 (100.00%)      0/3 (0.00%)      4/4 (100.00%)      6/9 (66.67%)      6/8 (75.00%)      11/14 (78.57%)      16/28 (57.14%)      12/19 (63.16%)      10/17 (58.82%)      3/10 (30.00%)      13/18 (72.22%)      25/31 (80.65%)      0/1 (0.00%)      2/2 (100.00%)      0/2 (0.00%)      2/3 (66.67%)      0/1 (0.00%)      2/3 (66.67%)    
Hide Serious Adverse Events
0.2_mg_kg_(LCNEC) 0.2_mg_kg_(NEPC) 0.2_mg_kg_(GEPNEC) 0.2_mg_kg_(Other_NEC) 0.2_mg_kg_(MM) 0.2_mg_kg_(MTC) 0.2_mg_kg_(GBM) 0.2_mg_kg_(Other_Solid) 0.3_mg_kg_(LCNEC) 0.3_mg_kg_(NEPC) 0.3_mg_kg_(GEPNEC) 0.3_mg_kg_(Other_NEC) 0.3_mg_kg_(MM) 0.3_mg_kg_(MTC) 0.3_mg_kg_(GBM) 0.3_mg_kg_(Other_Solid) 0.4_mg_kg_(GBM) 0.4_mg_kg_(GEPNEC) 0.4_mg_kg_(LCNEC) 0.4_mg_kg_(NEPC) 0.4_mg_kg_(Other_NEC) 0.4_mg_kg_(Other_Solid)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/3 (66.67%)      3/4 (75.00%)      2/6 (33.33%)      9/11 (81.82%)      2/3 (66.67%)      1/3 (33.33%)      2/4 (50.00%)      5/9 (55.56%)      6/8 (75.00%)      8/14 (57.14%)      15/28 (53.57%)      10/19 (52.63%)      8/17 (47.06%)      3/10 (30.00%)      8/18 (44.44%)      19/31 (61.29%)      0/1 (0.00%)      2/2 (100.00%)      1/2 (50.00%)      2/3 (66.67%)      0/1 (0.00%)      3/3 (100.00%)    
Blood and lymphatic system disorders                                             
Anaemia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pancytopenia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 1/19 (5.26%)  1 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Thrombocytopenia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0 0/3 (0.00%)  0
Cardiac disorders                                             
Atrial fibrillation  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 1/19 (5.26%)  1 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Atrial flutter  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pericardial effusion  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 1/4 (25.00%)  1 0/9 (0.00%)  0 1/8 (12.50%)  1 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 1/17 (5.88%)  1 1/10 (10.00%)  1 1/18 (5.56%)  1 1/31 (3.23%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 1/2 (50.00%)  2 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Supraventricular tachycardia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 1/17 (5.88%)  1 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Tachycardia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 1/17 (5.88%)  1 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Gastrointestinal disorders                                             
Abdominal distension  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Abdominal pain  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 2/28 (7.14%)  2 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 1/31 (3.23%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Ascites  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Constipation  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Diarrhoea  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 1/31 (3.23%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Duodenitis  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 1/10 (10.00%)  1 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Gastrointestinal haemorrhage  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 1/3 (33.33%)  2 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 2/31 (6.45%)  2 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Intestinal obstruction  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Nausea  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 2/31 (6.45%)  2 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pancreatitis acute  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 1/31 (3.23%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Small intestinal obstruction  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Upper gastrointestinal haemorrhage  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 1/10 (10.00%)  1 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Vomiting  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 2/31 (6.45%)  2 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
General disorders                                             
Fatigue  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Gait disturbance  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Generalised oedema  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 1/19 (5.26%)  1 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Infusion site extravasation  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Multiple organ dysfunction syndrome  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 1/31 (3.23%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Oedema peripheral  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 1/19 (5.26%)  1 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pyrexia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  2 2/28 (7.14%)  2 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Hepatobiliary disorders                                             
Bile duct obstruction  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Cholangitis acute  1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/6 (16.67%)  1 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Cholecystitis  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Cholecystitis acute  1  0/3 (0.00%)  0 0/4 (0.00%)  0 1/6 (16.67%)  1 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 /1  0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 /1  0/3 (0.00%)  0
Hepatic failure  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 /1  1/2 (50.00%)  2 0/2 (0.00%)  0 0/3 (0.00%)  0 /1  0/3 (0.00%)  0
Hepatotoxicity  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 /1  0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 /1  0/3 (0.00%)  0
Hyperbilirubinaemia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 /1  0/2 (0.00%)  0 0/2 (0.00%)  0 1/3 (33.33%)  1 /1  0/3 (0.00%)  0
Liver injury  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Infections and infestations                                             
Abdominal abscess  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 1/18 (5.56%)  1 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Bacteraemia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 1/18 (5.56%)  1 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Cellulitis  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Clostridial sepsis  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Corona virus infection  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Device related infection  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 1/19 (5.26%)  2 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Diverticulitis  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 1/10 (10.00%)  2 1/18 (5.56%)  2 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Escherichia bacteraemia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pneumonia  1  1/3 (33.33%)  1 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Rash pustular  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 1/3 (33.33%)  1
Sepsis  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 1/19 (5.26%)  1 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 1/31 (3.23%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Sepsis syndrome  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Urinary tract infection  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Urosepsis  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Injury, poisoning and procedural complications                                             
Postoperative wound complication  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 1/18 (5.56%)  1 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Subdural haematoma  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 1/31 (3.23%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Investigations                                             
Blood bilirubin increased  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Liver function test increased  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Transaminases increased  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Troponin increased  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 1/18 (5.56%)  1 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Metabolism and nutrition disorders                                             
Dehydration  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 4/31 (12.90%)  4 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Failure to thrive  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Fluid overload  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  2 1/28 (3.57%)  1 2/19 (10.53%)  2 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Hypercalcaemia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Hyperglycaemia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 1/18 (5.56%)  1 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Hypervolaemia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Hypokalaemia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Hyponatraemia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  2 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 1/31 (3.23%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Tumour lysis syndrome  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 1/19 (5.26%)  1 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders                                             
Arthralgia  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Back pain  1  0/3 (0.00%)  0 1/4 (25.00%)  1 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 1/28 (3.57%)  1 1/19 (5.26%)  1 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 1/31 (3.23%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Bone pain  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 1/2 (50.00%)  1 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Flank pain  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pain in extremity  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 1/31 (3.23%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pathological fracture  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Rhabdomyolysis  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 1/19 (5.26%)  1 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                                             
Malignant neoplasm progression  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 1/9 (11.11%)  1 2/8 (25.00%)  2 2/14 (14.29%)  2 7/28 (25.00%)  7 1/19 (5.26%)  1 1/17 (5.88%)  1 0/10 (0.00%)  0 3/18 (16.67%)  3 2/31 (6.45%)  3 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0 0/3 (0.00%)  0
Neoplasm malignant  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 1/28 (3.57%)  1 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Tumour haemorrhage  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 1/19 (5.26%)  1 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Tumour pain  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Nervous system disorders                                             
Brain oedema  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 1/18 (5.56%)  1 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Cerebral haemorrhage  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Cerebral infarction  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0 0/3 (0.00%)  0
Hepatic encephalopathy  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 1/31 (3.23%)  2 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Seizure  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/4 (25.00%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 2/18 (11.11%)  2 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Toxic encephalopathy  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Psychiatric disorders                                             
Confusional state  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/14 (7.14%)  1 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 1/31 (3.23%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Delirium  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 1/11 (9.09%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 0/17 (0.00%)  0 0/10 (0.00%)  0 0/18 (0.00%)  0 0/31 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Mental status changes  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0 0/19 (0.00%)  0 1/17 (5.88%)  1 0/10 (0.00%)  0 0/18 (0.00%)  0 1/31 (3.23%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/2 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Renal and urinary disorders                                             
Acute kidney injury  1  0/3 (0.00%)  0 0/4 (0.00%)  0 0/6 (0.00%)  0 0/11 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/4 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/14 (0.00%)  0 0/28 (0.00%)  0