A Study of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203)
Sponsor
Incyte Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT02318277
Collaborator
AstraZeneca (Industry)
176
13
1
69.4
13.5
0.2
Study Details
Study Description
Brief Summary
The purpose of this study is to explore the safety, tolerability, pharmacokinetics, immunogenicity and preliminary efficacy of INCB024360 administered in combination with MEDI4736 in subjects with selected advanced solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
176 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203)
Actual Study Start Date
:
Jan 5, 2015
Actual Primary Completion Date
:
Aug 28, 2019
Actual Study Completion Date
:
Oct 16, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MEDI4736 + INCB024360 MEDI4736 at selected dose levels every 2 weeks + INCB024360 25 mg BID as starting dose, followed by dose escalations until MTD or PAD is identified |
Drug: MEDI4736
MEDI4736 administered intravenously (IV) every two weeks (q2w)
Drug: INCB024360
INCB024360: Oral daily dosing
|
Outcome Measures
Primary Outcome Measures
- Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE) [Duration of study treatment and up to 90 days after the last dose [approximately 3 years]]
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment
- Phase 2: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [Measured every 8 weeks for duration of study treatment [approximately 12 months]]
ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Secondary Outcome Measures
- Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1 [Measured every 8 weeks for duration of study treatment [approximately 6 months]]
ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Phase 2: Number of Treatment-Emergent Adverse Events [Continuously for duration of study treatment and up to 90 days after the last dose [approximately 3 years]]
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment
- Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression [Measured every 8 weeks for duration of active study treatment [approximately 24 months]]
Defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1, or death due to any cause, if occurring sooner than progression.
- Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death [Measured every 8 weeks for duration of active study treatment [approximately 24 months]]
- Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration [Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1]
- Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration [Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1]
- Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve [Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1]
- Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs) [Measured at defined study visits from Cycle 1 Day 1 through cycle 2 [approximately 2 weeks].]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female subjects, age 18 years or older
-
Histologically or cytologically confirmed diagnosis of selected locally advanced or metastatic solid tumors
-
Must have failed at least 1 prior treatment regimen for locally advanced or metastatic disease or be intolerant to treatment or refuse standard treatment
Exclusion Criteria:
-
Laboratory and medical history parameters not within protocol-defined range
-
Participation in any other study in which receipt of an investigational study drug occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose
-
Prior treatment with immune checkpoint inhibitors (eg, anti-CTLA-4, anti-PD-1, anti-PD-L1, and any other antibody or drug specifically targeting T-cell co-stimulation) or an IDO inhibitor (exception is tumor types in which a PD-1 pathway targeted agent is approved, e.g. melanoma, non-small cell lung cancer.)
-
Receipt of any anticancer medication in the 21 days prior to receiving the first dose of study medication
-
Has an active or inactive autoimmune process
-
Evidence of interstitial lung disease or active, non-infectious pneumonitis
-
Prior radiotherapy within 2 weeks of initiating treatment; Must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
-
Untreated central nervous system (CNS) metastases or CNS metastases that have progressed
-
Currently pregnant or breastfeeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | San Francisco | California | United States | ||
| 2 | Denver | Colorado | United States | ||
| 3 | Miami | Florida | United States | ||
| 4 | Port Saint Lucie | Florida | United States | ||
| 5 | Sarasota | Florida | United States | ||
| 6 | Tampa | Florida | United States | ||
| 7 | Chicago | Illinois | United States | ||
| 8 | Louisville | Kentucky | United States | ||
| 9 | Durham | North Carolina | United States | ||
| 10 | Huntersville | North Carolina | United States | ||
| 11 | Winston-Salem | North Carolina | United States | ||
| 12 | Dallas | Texas | United States | ||
| 13 | Houston | Texas | United States |
Sponsors and Collaborators
- Incyte Corporation
- AstraZeneca
Investigators
- Study Director: Lance Leopold, MD, Incyte Corporation
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT02318277
Other Study ID Numbers:
- INCB 24360-203 / ECHO-203
First Posted:
Dec 17, 2014
Last Update Posted:
Jan 13, 2022
Last Verified:
Jan 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study was conducted at 13 study sites in the United States. Participants were enrolled at 12 study sites. |
|---|---|
| Pre-assignment Detail | A total of 235 participants were screened and 59 participants were screen failures. A total of 176 participants ( 34 participants in Phase 1 and 142 in Phase 2) were enrolled in the study. Study enrollment was permanently discontinued on 24 Apr 2018 as a strategic decision. At the time of data cut-off, 28 Aug 2019, 1 participant was ongoing. |
| Arm/Group Title | Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. |
| Period Title: Overall Study | ||||||||
| STARTED | 6 | 3 | 4 | 4 | 8 | 9 | 49 | 93 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 3 | 4 | 4 | 8 | 9 | 49 | 93 |
Baseline Characteristics
| Arm/Group Title | Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | Total of all reporting groups |
| Overall Participants | 6 | 3 | 4 | 4 | 8 | 9 | 49 | 93 | 176 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [Years] |
70.8
(4.79)
|
75.7
(7.23)
|
65.3
(9.07)
|
72.3
(7.59)
|
58.6
(8.65)
|
63.4
(7.75)
|
60.2
(13.24)
|
64
(10.27)
|
63.3
(11.11)
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
3
50%
|
2
66.7%
|
1
25%
|
1
25%
|
1
12.5%
|
5
55.6%
|
19
38.8%
|
25
26.9%
|
57
32.4%
|
| Male |
3
50%
|
1
33.3%
|
3
75%
|
3
75%
|
7
87.5%
|
4
44.4%
|
30
61.2%
|
68
73.1%
|
119
67.6%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||||
| White |
6
100%
|
3
100%
|
4
100%
|
4
100%
|
7
87.5%
|
9
100%
|
41
83.7%
|
83
89.2%
|
157
89.2%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
5
10.2%
|
5
5.4%
|
11
6.3%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2%
|
3
3.2%
|
4
2.3%
|
| Other |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2%
|
2
2.2%
|
3
1.7%
|
| Missing |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2%
|
0
0%
|
1
0.6%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||||
| Hispanic or Latino |
2
33.3%
|
0
0%
|
0
0%
|
1
25%
|
0
0%
|
0
0%
|
1
2%
|
3
3.2%
|
7
4%
|
| Not Hispanic or Latino |
4
66.7%
|
3
100%
|
4
100%
|
3
75%
|
8
100%
|
9
100%
|
46
93.9%
|
87
93.5%
|
164
93.2%
|
| Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.1%
|
1
0.6%
|
| Unknown |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
4.1%
|
2
2.2%
|
4
2.3%
|
Outcome Measures
| Title | Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE) |
|---|---|
| Description | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment |
| Time Frame | Duration of study treatment and up to 90 days after the last dose [approximately 3 years] |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Phase 1 safety population includes all subjects enrolled in the Phase 1 portion of the study who received at least 1 dose of INCB024360 or MEDI4736. Treatment groups were determined according to the actual treatment the subject received on Day 1 regardless of the actual study drug the subject received during participation in the study. |
| Arm/Group Title | Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. |
| Measure Participants | 6 | 3 | 4 | 4 | 8 | 9 |
| Count of Participants [Participants] |
6
100%
|
3
100%
|
4
100%
|
4
100%
|
8
100%
|
9
100%
|
| Title | Phase 2: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
|---|---|
| Description | ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
| Time Frame | Measured every 8 weeks for duration of study treatment [approximately 12 months] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population : All subjects who are enrolled in the Phase 2 portion of the study. |
| Arm/Group Title | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) |
|---|---|---|
| Arm/Group Description | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. |
| Measure Participants | 49 | 93 |
| Count of Participants [Participants] |
6
100%
|
12
400%
|
| Title | Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1 |
|---|---|
| Description | ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
| Time Frame | Measured every 8 weeks for duration of study treatment [approximately 6 months] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population: All subjects who are enrolled in the Phase 1 portion of the study. Treatment groups for this population were defined according to the treatment assignment at the time of enrollment on Day 1 regardless of the actual study drug the subject received during his/her continued participation in the study. |
| Arm/Group Title | Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. |
| Measure Participants | 6 | 3 | 4 | 4 | 8 | 9 |
| Count of Participants [Participants] |
1
16.7%
|
0
0%
|
1
25%
|
0
0%
|
1
12.5%
|
2
22.2%
|
| Title | Phase 2: Number of Treatment-Emergent Adverse Events |
|---|---|
| Description | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment |
| Time Frame | Continuously for duration of study treatment and up to 90 days after the last dose [approximately 3 years] |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Phase 2 safety population includes all subjects enrolled in the Phase 2 portion of the study who received at least 1 dose of INCB024360 or MEDI4736. |
| Arm/Group Title | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) |
|---|---|---|
| Arm/Group Description | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. |
| Measure Participants | 49 | 93 |
| Count of Participants [Participants] |
49
816.7%
|
93
3100%
|
| Title | Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression |
|---|---|
| Description | Defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1, or death due to any cause, if occurring sooner than progression. |
| Time Frame | Measured every 8 weeks for duration of active study treatment [approximately 24 months] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population: All subjects who are enrolled in the Phase 1 & 2 portion of the study. Treatment groups were defined at the time of enrollment on Day 1 according to the treatment assignment for Phase 1 and according to the tumor type for phase 2. |
| Arm/Group Title | Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. |
| Measure Participants | 1 | 0 | 1 | 0 | 1 | 2 | 6 | 12 |
| Median (95% Confidence Interval) [months] |
1.9
|
NA
|
NA
|
NA
|
13.8
|
NA
|
| Title | Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death |
|---|---|
| Description | |
| Time Frame | Measured every 8 weeks for duration of active study treatment [approximately 24 months] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Population: All subjects who are enrolled in the Phase 1 & 2 portion of the study. Treatment groups were defined at the time of enrollment on Day 1 according to the treatment assignment for Phase 1 and according to the tumor type for phase 2. |
| Arm/Group Title | Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. |
| Measure Participants | 6 | 3 | 4 | 4 | 8 | 9 | 49 | 93 |
| Median (95% Confidence Interval) [Months] |
2.4
|
12.0
|
1.9
|
1.7
|
4.1
|
2.5
|
1.9
|
2.1
|
| Title | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration |
|---|---|
| Description | |
| Time Frame | Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK evaluable population will include all subjects who received at least 1 dose of INCB024360 and provided at least 1 post dose plasma sample (1 PK/PD measurement). Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg)" Arm/Group were combined with the data collected from participants in the "Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg)" Arm/Group for PK Analysis. |
| Arm/Group Title | Phase I : Epacadostat (25 mg) + Durvalumab | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 or 10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. |
| Measure Participants | 8 | 3 | 3 | 7 | 7 | 38 | 36 |
| Mean (Standard Deviation) [nM] |
273
(65.3)
|
248
(135)
|
604
(493)
|
727
(403)
|
2660
(1200)
|
960
(499)
|
2500
(1190)
|
| Title | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration |
|---|---|
| Description | |
| Time Frame | Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK evaluable population will include all subjects who received at least 1 dose of INCB024360 and provided at least 1 post dose plasma sample (1 PK/PD measurement). Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg)" Arm/Group were combined with the data collected from participants in the "Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg)" Arm/Group for PK Analysis. |
| Arm/Group Title | Phase I : Epacadostat (25 mg) + Durvalumab | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 or 10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. |
| Measure Participants | 8 | 3 | 3 | 7 | 7 | 38 | 36 |
| Median (Full Range) [hours] |
2.0
|
2.0
|
1.9
|
2.0
|
3.3
|
2.0
|
2.1
|
| Title | Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve |
|---|---|
| Description | |
| Time Frame | Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK evaluable population will include all subjects who received at least 1 dose of INCB024360 and provided at least 1 post dose plasma sample (1 PK/PD measurement). Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg)" Arm/Group were combined with the data collected from participants in the "Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg)" Arm/Group for PK Analysis. |
| Arm/Group Title | Phase I : Epacadostat (25 mg) + Durvalumab | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 or 10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. |
| Measure Participants | 8 | 3 | 3 | 7 | 7 | 36 | 34 |
| Mean (Standard Deviation) [h*nM] |
1040
(345)
|
1580
(739)
|
3090
(1880)
|
3650
(2710)
|
15400
(6770)
|
4130
(1960)
|
12200
(5950)
|
| Title | Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs) |
|---|---|
| Description | |
| Time Frame | Measured at defined study visits from Cycle 1 Day 1 through cycle 2 [approximately 2 weeks]. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable Patients Post-Baseline: Treatment-Induced ADA - Patients who had baseline negative ADA result who developed anti-drug antibodies at any time after initial drug administration. |
| Arm/Group Title | Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg)Edit | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg)Edit | Phase 2 Stage 1: Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase 2 Stage 2: Epacadostat (300 mg) + Durvalumab (10 mg/kg) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle to determine maximum Tolerated dose (MTD) or pharmacologically active dose (PAD). | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle to determine maximum Tolerated dose (MTD) or pharmacologically active dose (PAD). |
| Measure Participants | 4 | 2 | 3 | 3 | 7 | 8 | 36 | 0 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Duration of study treatment and up to 90 days after the last dose [approximately 3 years] | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||
| Arm/Group Title | Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | ||||||||
| Arm/Group Description | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (3 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (25 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (50 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (75 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle. | Epacadostat (100 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | Epacadostat (300 mg) oral twice-daily (BID) dosing in combination with durvalumab (10 mg/kg) administered intravenously (IV) on Day 1 of each 14 day cycle in select tumor types. | ||||||||
All Cause Mortality |
||||||||||||||||
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | |||||||||
| 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 | 5/6 (83.3%) | 3/3 (100%) | 1/4 (25%) | 4/4 (100%) | 6/8 (75%) | 5/9 (55.6%) | 35/49 (71.4%) | 58/93 (62.4%) | ||||||||
Serious Adverse Events |
||||||||||||||||
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | |||||||||
| 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 | 2/6 (33.3%) | 0/3 (0%) | 2/4 (50%) | 0/4 (0%) | 4/8 (50%) | 3/9 (33.3%) | 20/49 (40.8%) | 54/93 (58.1%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Anaemia | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 4/93 (4.3%) | 4 |
| Leukocytosis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Cardiac disorders | ||||||||||||||||
| Atrial fibrillation | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 2/93 (2.2%) | 2 |
| Cardiac failure congestive | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Pericardial effusion | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 2/93 (2.2%) | 2 |
| Pulseless electrical activity | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Sinus tachycardia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Supraventricular tachycardia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Tachycardia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 1/93 (1.1%) | 1 |
| Eye disorders | ||||||||||||||||
| Vision blurred | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/8 (25%) | 2 | 0/9 (0%) | 0 | 3/49 (6.1%) | 4 | 1/93 (1.1%) | 1 |
| Ascites | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Colitis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 2/93 (2.2%) | 2 |
| Constipation | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 2/93 (2.2%) | 2 |
| Diarrhoea | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Dysphagia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 2 | 0/49 (0%) | 0 | 3/93 (3.2%) | 3 |
| Gastric haemorrhage | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Intestinal perforation | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Large intestinal obstruction | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Nausea | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 3 | 2/93 (2.2%) | 2 |
| Small intestinal obstruction | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 2 | 0/93 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 1/93 (1.1%) | 1 |
| Vomiting | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 4/49 (8.2%) | 5 | 3/93 (3.2%) | 3 |
| General disorders | ||||||||||||||||
| Asthenia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 3/93 (3.2%) | 3 |
| Chest pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Disease progression | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 1/93 (1.1%) | 1 |
| Face oedema | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Fatigue | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 4/93 (4.3%) | 5 |
| Localised oedema | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Multi-organ failure | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Non-cardiac chest pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Oedema peripheral | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 2/93 (2.2%) | 2 |
| Pyrexia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 3/93 (3.2%) | 3 |
| Hepatobiliary disorders | ||||||||||||||||
| Bile duct stenosis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Hepatic failure | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Hyperbilirubinaemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 2/93 (2.2%) | 2 |
| Immune system disorders | ||||||||||||||||
| Anaphylactic reaction | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Infections and infestations | ||||||||||||||||
| Bacteraemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Cellulitis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 2/93 (2.2%) | 3 |
| Device related sepsis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Lung infection | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Pneumonia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 5/93 (5.4%) | 6 |
| Sepsis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 4/93 (4.3%) | 5 |
| Skin infection | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Soft tissue infection | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Urinary tract infection | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 3/93 (3.2%) | 4 |
| Urosepsis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||
| Contrast media reaction | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Fall | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Infusion related reaction | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Spinal compression fracture | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Wound | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Investigations | ||||||||||||||||
| Alanine aminotransferase increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Amylase increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Aspartate aminotransferase increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Blood alkaline phosphatase increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Blood calcium increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Blood creatinine increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 1/93 (1.1%) | 1 |
| Lipase increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||
| Decreased appetite | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Dehydration | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 5/93 (5.4%) | 5 |
| Hyperglycaemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Hypoalbuminaemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Hyponatraemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Arthralgia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Back pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Neck pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 0/93 (0%) | 0 |
| Pain in extremity | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Malignant neoplasm progression | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 2/93 (2.2%) | 2 |
| Metastases to central nervous system | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 1/93 (1.1%) | 1 |
| Squamous cell carcinoma of head and neck | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Tumour pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 4/93 (4.3%) | 5 |
| Nervous system disorders | ||||||||||||||||
| Cerebrovascular accident | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Convulsion | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 2/93 (2.2%) | 2 |
| Depressed level of consciousness | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Dizziness | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 2/93 (2.2%) | 2 |
| Hypoaesthesia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Polyneuropathy | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Presyncope | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Subarachnoid haemorrhage | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Syncope | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 2/93 (2.2%) | 2 |
| Transient ischaemic attack | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 2/93 (2.2%) | 2 |
| Psychiatric disorders | ||||||||||||||||
| Agitation | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Confusional state | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Delirium | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Renal and urinary disorders | ||||||||||||||||
| Haematuria | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Renal failure acute | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 2/93 (2.2%) | 2 |
| Urinary tract obstruction | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 2/93 (2.2%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Chronic obstructive pulmonary disease | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Cough | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Dyspnoea | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 5/49 (10.2%) | 7 | 4/93 (4.3%) | 4 |
| Hypoxia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 2 |
| Laryngeal haemorrhage | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Pharyngeal haemorrhage | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 2/93 (2.2%) | 2 |
| Pleural effusion | 1/6 (16.7%) | 2 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 2/93 (2.2%) | 2 |
| Pneumonia aspiration | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Pneumothorax | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Pulmonary haemorrhage | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Stridor | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Rash maculo-papular | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Vascular disorders | ||||||||||||||||
| Angiopathy | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Deep vein thrombosis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Embolism | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 1/93 (1.1%) | 1 |
| Hypertensive emergency | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Hypotension | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 4/93 (4.3%) | 4 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/kg) | Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase I : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (100 mg) + Durvalumab (10 mg/kg) | Phase II : Epacadostat (300 mg) + Durvalumab (10 mg/kg) | |||||||||
| 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 | 6/6 (100%) | 3/3 (100%) | 4/4 (100%) | 4/4 (100%) | 8/8 (100%) | 9/9 (100%) | 48/49 (98%) | 87/93 (93.5%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Anaemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 3/9 (33.3%) | 3 | 11/49 (22.4%) | 11 | 11/93 (11.8%) | 13 |
| Leukocytosis | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 3/49 (6.1%) | 5 | 4/93 (4.3%) | 4 |
| Leukopenia | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Neutropenia | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||
| Angina pectoris | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Palpitations | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Tachycardia | 2/6 (33.3%) | 2 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 3 | 0/49 (0%) | 0 | 3/93 (3.2%) | 3 |
| Ear and labyrinth disorders | ||||||||||||||||
| Tinnitus | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 2/93 (2.2%) | 3 |
| Endocrine disorders | ||||||||||||||||
| Hyperthyroidism | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 1/93 (1.1%) | 1 |
| Hypogonadism | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Hypothyroidism | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 7/93 (7.5%) | 7 |
| Eye disorders | ||||||||||||||||
| Cataract | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 1/93 (1.1%) | 1 |
| Conjunctivitis allergic | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Dry eye | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Vision blurred | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 3/49 (6.1%) | 3 | 4/93 (4.3%) | 4 |
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal distension | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/8 (25%) | 2 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 4/93 (4.3%) | 4 |
| Abdominal pain | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/8 (12.5%) | 2 | 2/9 (22.2%) | 2 | 5/49 (10.2%) | 5 | 10/93 (10.8%) | 10 |
| Abdominal pain lower | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Abdominal pain upper | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/8 (37.5%) | 3 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 2/93 (2.2%) | 2 |
| Constipation | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 2/4 (50%) | 2 | 0/4 (0%) | 0 | 2/8 (25%) | 2 | 1/9 (11.1%) | 1 | 11/49 (22.4%) | 11 | 20/93 (21.5%) | 21 |
| Dental caries | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Diarrhoea | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 2/8 (25%) | 3 | 3/9 (33.3%) | 4 | 10/49 (20.4%) | 15 | 22/93 (23.7%) | 28 |
| Dry mouth | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 2/9 (22.2%) | 2 | 0/49 (0%) | 0 | 4/93 (4.3%) | 6 |
| Dysphagia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 2/9 (22.2%) | 2 | 3/49 (6.1%) | 3 | 5/93 (5.4%) | 5 |
| Epigastric discomfort | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Flatulence | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Gastric ulcer | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Gastritis | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 2/93 (2.2%) | 3 |
| Gastrointestinal pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 4/93 (4.3%) | 4 |
| Haemorrhoidal haemorrhage | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Impaired gastric emptying | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Melaena | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Nausea | 4/6 (66.7%) | 4 | 1/3 (33.3%) | 1 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 4/8 (50%) | 6 | 3/9 (33.3%) | 4 | 13/49 (26.5%) | 19 | 28/93 (30.1%) | 33 |
| Small intestinal obstruction | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Stomatitis | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 3/49 (6.1%) | 3 | 8/93 (8.6%) | 9 |
| Vomiting | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 3/8 (37.5%) | 3 | 3/9 (33.3%) | 5 | 7/49 (14.3%) | 10 | 17/93 (18.3%) | 20 |
| General disorders | ||||||||||||||||
| Asthenia | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 2/93 (2.2%) | 2 |
| Catheter site discharge | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Chills | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 6/49 (12.2%) | 7 | 8/93 (8.6%) | 10 |
| Face oedema | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 2 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Fatigue | 4/6 (66.7%) | 4 | 1/3 (33.3%) | 1 | 2/4 (50%) | 3 | 2/4 (50%) | 2 | 3/8 (37.5%) | 5 | 2/9 (22.2%) | 2 | 25/49 (51%) | 28 | 50/93 (53.8%) | 54 |
| Influenza like illness | 2/6 (33.3%) | 2 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 5/93 (5.4%) | 5 |
| Non-cardiac chest pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 5/93 (5.4%) | 5 |
| Oedema peripheral | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 3/8 (37.5%) | 5 | 0/9 (0%) | 0 | 5/49 (10.2%) | 5 | 9/93 (9.7%) | 10 |
| Pyrexia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 0/4 (0%) | 0 | 3/8 (37.5%) | 3 | 1/9 (11.1%) | 2 | 11/49 (22.4%) | 12 | 10/93 (10.8%) | 15 |
| Infections and infestations | ||||||||||||||||
| Bronchitis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Candida infection | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 1/9 (11.1%) | 2 | 0/49 (0%) | 0 | 2/93 (2.2%) | 2 |
| Clostridium difficile colitis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Eye infection | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Nasopharyngitis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Oral candidiasis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 2/93 (2.2%) | 2 |
| Pneumonia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Skin infection | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 5/93 (5.4%) | 5 |
| Upper respiratory tract infection | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 5/93 (5.4%) | 9 |
| Urinary tract infection | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 5/49 (10.2%) | 5 | 5/93 (5.4%) | 6 |
| Injury, poisoning and procedural complications | ||||||||||||||||
| Fall | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 4/49 (8.2%) | 4 | 7/93 (7.5%) | 9 |
| Foreign body aspiration | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Laceration | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Skin abrasion | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Tooth fracture | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Investigations | ||||||||||||||||
| Alanine aminotransferase increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 3/9 (33.3%) | 3 | 3/49 (6.1%) | 3 | 10/93 (10.8%) | 13 |
| Amylase increased | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 3/49 (6.1%) | 3 | 6/93 (6.5%) | 11 |
| Aspartate aminotransferase increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 3/9 (33.3%) | 3 | 5/49 (10.2%) | 5 | 11/93 (11.8%) | 13 |
| Blood albumin decreased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 3/93 (3.2%) | 3 |
| Blood alkaline phosphatase increased | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 2/9 (22.2%) | 2 | 3/49 (6.1%) | 3 | 12/93 (12.9%) | 13 |
| Blood bilirubin increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Blood creatinine increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 2/9 (22.2%) | 2 | 4/49 (8.2%) | 4 | 15/93 (16.1%) | 18 |
| Blood potassium decreased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 3/49 (6.1%) | 3 | 0/93 (0%) | 0 |
| Blood prolactin abnormal | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 3/49 (6.1%) | 3 | 5/93 (5.4%) | 5 |
| Blood testosterone decreased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Ejection fraction decreased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| International normalised ratio increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 2 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Lipase increased | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 5/49 (10.2%) | 8 | 9/93 (9.7%) | 10 |
| Lymphocyte count decreased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 3/49 (6.1%) | 3 | 2/93 (2.2%) | 5 |
| Transaminases increased | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Weight decreased | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/8 (25%) | 2 | 2/9 (22.2%) | 2 | 1/49 (2%) | 1 | 6/93 (6.5%) | 6 |
| Metabolism and nutrition disorders | ||||||||||||||||
| Decreased appetite | 2/6 (33.3%) | 2 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 1/8 (12.5%) | 1 | 2/9 (22.2%) | 2 | 9/49 (18.4%) | 12 | 26/93 (28%) | 26 |
| Dehydration | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 5/49 (10.2%) | 6 | 14/93 (15.1%) | 17 |
| Hypercalcaemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 3 | 7/93 (7.5%) | 7 |
| Hyperglycaemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 3 | 5/49 (10.2%) | 12 | 8/93 (8.6%) | 23 |
| Hyperkalaemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 2/49 (4.1%) | 2 | 4/93 (4.3%) | 6 |
| Hyperuricaemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 3/49 (6.1%) | 5 | 5/93 (5.4%) | 6 |
| Hypoalbuminaemia | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/8 (25%) | 2 | 0/9 (0%) | 0 | 4/49 (8.2%) | 5 | 6/93 (6.5%) | 6 |
| Hypoglycaemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 1/93 (1.1%) | 1 |
| Hypokalaemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 2/49 (4.1%) | 3 | 8/93 (8.6%) | 8 |
| Hypomagnesaemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 5/93 (5.4%) | 7 |
| Hyponatraemia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 3 | 4/49 (8.2%) | 4 | 8/93 (8.6%) | 10 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Arthralgia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 2/9 (22.2%) | 3 | 6/49 (12.2%) | 7 | 9/93 (9.7%) | 15 |
| Arthritis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 1/93 (1.1%) | 1 |
| Back pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/8 (25%) | 2 | 0/9 (0%) | 0 | 7/49 (14.3%) | 7 | 10/93 (10.8%) | 10 |
| Bone pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 2/49 (4.1%) | 2 | 2/93 (2.2%) | 2 |
| Muscle spasms | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 2/93 (2.2%) | 3 |
| Muscular weakness | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 3/49 (6.1%) | 3 | 4/93 (4.3%) | 4 |
| Musculoskeletal chest pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 4/49 (8.2%) | 4 | 4/93 (4.3%) | 4 |
| Musculoskeletal pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 3/49 (6.1%) | 3 | 5/93 (5.4%) | 7 |
| Myalgia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 4/49 (8.2%) | 6 | 14/93 (15.1%) | 16 |
| Neck pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 7/49 (14.3%) | 7 | 5/93 (5.4%) | 5 |
| Pain in extremity | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 3/49 (6.1%) | 4 | 8/93 (8.6%) | 8 |
| Spinal pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Malignant ascites | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Peritumoural oedema | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Tumour flare | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 3/93 (3.2%) | 3 |
| Tumour pain | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 2/9 (22.2%) | 2 | 1/49 (2%) | 2 | 9/93 (9.7%) | 9 |
| Nervous system disorders | ||||||||||||||||
| Dizziness | 1/6 (16.7%) | 3 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 5/49 (10.2%) | 5 | 9/93 (9.7%) | 10 |
| Dysgeusia | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 4/93 (4.3%) | 5 |
| Headache | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 2/4 (50%) | 2 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 6/49 (12.2%) | 8 | 16/93 (17.2%) | 20 |
| Neuropathy peripheral | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 5/93 (5.4%) | 5 |
| Paraesthesia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 1/93 (1.1%) | 1 |
| Serotonin syndrome | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Sinus headache | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Somnolence | 2/6 (33.3%) | 2 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 1/93 (1.1%) | 1 |
| Syncope | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 2/93 (2.2%) | 2 |
| Vocal cord paralysis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||
| Anxiety | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 4/49 (8.2%) | 4 | 6/93 (6.5%) | 7 |
| Confusional state | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 2/93 (2.2%) | 2 |
| Depression | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 2/49 (4.1%) | 2 | 4/93 (4.3%) | 4 |
| Insomnia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 5/49 (10.2%) | 5 | 16/93 (17.2%) | 16 |
| Renal and urinary disorders | ||||||||||||||||
| Haematuria | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Hydronephrosis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Lower urinary tract symptoms | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Urinary retention | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||
| Breast mass | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Erectile dysfunction | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Atelectasis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Cough | 2/6 (33.3%) | 2 | 2/3 (66.7%) | 2 | 1/4 (25%) | 1 | 2/4 (50%) | 3 | 1/8 (12.5%) | 1 | 2/9 (22.2%) | 2 | 7/49 (14.3%) | 9 | 19/93 (20.4%) | 26 |
| Dyspnoea | 1/6 (16.7%) | 2 | 1/3 (33.3%) | 2 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 5/49 (10.2%) | 7 | 13/93 (14%) | 18 |
| Dyspnoea exertional | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 3/49 (6.1%) | 3 | 1/93 (1.1%) | 1 |
| Haemoptysis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 4/93 (4.3%) | 4 |
| Hiccups | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Hypoxia | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 2/93 (2.2%) | 2 |
| Laryngeal inflammation | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Nasal congestion | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 2/49 (4.1%) | 2 | 5/93 (5.4%) | 5 |
| Oropharyngeal pain | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 2/93 (2.2%) | 2 |
| Pleural effusion | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 2/8 (25%) | 2 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Pneumonia aspiration | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Pneumonitis | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Rales | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Rhonchi | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Sputum discoloured | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Throat irritation | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 0/9 (0%) | 0 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Upper-airway cough syndrome | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 3/49 (6.1%) | 3 | 3/93 (3.2%) | 3 |
| Wheezing | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 2/49 (4.1%) | 2 | 2/93 (2.2%) | 2 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Alopecia | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 1/93 (1.1%) | 1 |
| Erythema | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Hyperhidrosis | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 0/93 (0%) | 0 |
| Pruritus | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 2/8 (25%) | 2 | 3/9 (33.3%) | 4 | 4/49 (8.2%) | 5 | 13/93 (14%) | 17 |
| Rash | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 3/49 (6.1%) | 4 | 10/93 (10.8%) | 11 |
| Rash macular | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 0/93 (0%) | 0 |
| Rash maculo-papular | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/4 (25%) | 3 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 2 | 9/49 (18.4%) | 14 | 10/93 (10.8%) | 13 |
| Swelling face | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 1/9 (11.1%) | 1 | 0/49 (0%) | 0 | 2/93 (2.2%) | 2 |
| Vascular disorders | ||||||||||||||||
| Hypertension | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/8 (12.5%) | 1 | 1/9 (11.1%) | 1 | 1/49 (2%) | 1 | 6/93 (6.5%) | 8 |
| Hypotension | 2/6 (33.3%) | 3 | 0/3 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/8 (0%) | 0 | 0/9 (0%) | 0 | 1/49 (2%) | 1 | 5/93 (5.4%) | 5 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Clinical Study Agreement
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Incyte Corporation |
| Phone | 855-463-3463 |
| medinfo@incyte.com |
Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT02318277
Other Study ID Numbers:
- INCB 24360-203 / ECHO-203
First Posted:
Dec 17, 2014
Last Update Posted:
Jan 13, 2022
Last Verified:
Jan 1, 2022