Trial Outcomes & Findings for A Phase 1b/2 Study of MEDI4736 With Tremelimumab, MEDI4736 or Tremelimumab Monotherapy in Gastric or GEJ Adenocarcinoma (NCT NCT02340975)
NCT ID: NCT02340975
Last Updated: 2020-06-09
Results Overview
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
114 participants
Primary outcome timeframe
Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Results posted on
2020-06-09
Participant Flow
The study was conducted in the United States of America, Japan, Korea, Taiwan and Singapore between 31Mar2015 and 29Apr2019.
A total of 114 participants were randomized in the study, out of which 113 participants received study treatment.
Participant milestones
| Measure |
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
27
|
24
|
12
|
25
|
19
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
27
|
24
|
12
|
25
|
19
|
Reasons for withdrawal
| Measure |
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|---|
|
Overall Study
Death
|
6
|
23
|
21
|
7
|
21
|
13
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
0
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
3
|
3
|
2
|
0
|
|
Overall Study
Other
|
0
|
4
|
0
|
2
|
0
|
6
|
Baseline Characteristics
A Phase 1b/2 Study of MEDI4736 With Tremelimumab, MEDI4736 or Tremelimumab Monotherapy in Gastric or GEJ Adenocarcinoma
Baseline characteristics by cohort
| Measure |
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Total
n=113 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
70.0 Years
STANDARD_DEVIATION 12.7 • n=5 Participants
|
60.4 Years
STANDARD_DEVIATION 13.5 • n=7 Participants
|
59.8 Years
STANDARD_DEVIATION 12.0 • n=5 Participants
|
52.3 Years
STANDARD_DEVIATION 16.0 • n=4 Participants
|
58.6 Years
STANDARD_DEVIATION 10.7 • n=21 Participants
|
59.9 Years
STANDARD_DEVIATION 12.8 • n=8 Participants
|
59.4 Years
STANDARD_DEVIATION 12.9 • n=8 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
30 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
14 Participants
n=8 Participants
|
83 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
25 Participants
n=21 Participants
|
18 Participants
n=8 Participants
|
111 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
13 Participants
n=8 Participants
|
49 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
63 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Day 1 up to 90 days after the last dose (approximately 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 1b
TEAEs
|
—
|
6 Participants
|
—
|
—
|
—
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 1b
TESAEs
|
—
|
2 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From first dose of Study drug (Day 1) through 28 days after the administration of MEDI4736 and tremelimumabPopulation: Dose limiting toxicity (DLT) evaluable population included all participants in the Phase 1b who received the Study drug and completed safety follow-up through the DLT evaluation period or experience a DLT during the DLT evaluation period (From first dose of Study drug \[Day 1\] through 28 days after the administration of MEDI4736 and tremelimumab).
A DLT was defined as any Grade 3 or higher toxicity that occurs during the DLT evaluation period (From first dose of Study drug \[Day 1\] through 28 days after the administration of MEDI4736 and tremelimumab). The DLTs are: any Grade 4 immune-related adverse event (irAE), any Grade \>=3 non-irAE, \>= Grade 3 colitis, Grade 3 or 4 noninfectious pneumonitis irrespective of duration, Grade 2 pneumonitis, liver transaminase elevation \> 8 × upper limit of normal (ULN) or total bilirubin \> 5 × ULN. Immune-related AEs are defined as AEs of an immune nature (ie, inflammatory) in the absence of a clear alternative etiology.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1b
|
—
|
1 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 up to 90 days after the last dose (approximately 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
Anaemia
|
—
|
1 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
Lymphopenia
|
—
|
1 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
Haemoglobin decreased
|
—
|
1 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
Prothrombin time prolonged
|
—
|
1 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
Activated partial thromboplastin time prolonged
|
—
|
1 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
Blood alkaline phosphatase increased
|
—
|
1 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
Blood bilirubin increased
|
—
|
1 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
Gamma-glutamyltransferase increased
|
—
|
2 Participants
|
—
|
—
|
—
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
Transaminases increased
|
—
|
1 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 up to 90 days after the last dose (approximately 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure \[BP\], pulse rate \[or pulse oximetry at screening\], and respiratory rate). Abnormal physical examinations are defined as any abnormal impact on measurements of height and weight.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 1b
Pyrexia
|
—
|
1 Participants
|
—
|
—
|
—
|
|
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 1b
Weight decreased
|
—
|
1 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 up to 90 days after the last dose (approximately 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, PR, RR, QRS and QT intervals from the primary lead of the digital 12-lead ECG.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 1b
|
—
|
1 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (Day 1)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
The ECOG scale of performance status describes the level of functioning of participants in terms of their ability to care for themselves, daily activity, and physical ability. ECOG Performance Status Scorings are: 0= fully active, able to carry on all pre-disease performance without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (for example, light house work, office work); 2= ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5= dead. The baseline performance status of participants is presented.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b
ECOG 0
|
—
|
4 Participants
|
—
|
—
|
—
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b
ECOG 1
|
—
|
2 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
OR: best overall response (BOR) of confirmed complete response (CR) or partial response (PR) per RECIST v1.1. BOR: best response (CR, PR, stable disease \[SD\], progressive disease \[PD\], and not evaluable) among all overall responses recorded from date of randomization for Arm A, B, C participants or date of first dose of study drug for Arms D, E participants until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study; PD: at least 20% increase in SOD of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Percentage of Participants With Objective Response (OR) in Phase 2
|
4.0 Percentage of participants
Interval 0.1 to 20.4
|
11.1 Percentage of participants
Interval 2.4 to 29.2
|
0 Percentage of participants
Interval 0.0 to 14.2
|
8.3 Percentage of participants
Interval 0.2 to 38.5
|
15.8 Percentage of participants
Interval 3.4 to 39.6
|
PRIMARY outcome
Timeframe: From Day 1 upto 6 monthsPopulation: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
The PFS-6 is the 6-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 6 months. PFS was defined as the time from the date of first dose of study drug for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS-6.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Progression Free Survival at 6 (PFS-6) Month in Phase 2
|
12.5 Percentage of participants
Interval 3.1 to 28.7
|
12.1 Percentage of participants
Interval 3.1 to 27.9
|
NA Percentage of participants
No participants were progression free at 6 months.
|
23.3 Percentage of participants
Interval 3.6 to 52.9
|
5.3 Percentage of participants
Interval 0.4 to 21.4
|
SECONDARY outcome
Timeframe: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
OR: best overall response (BOR) of confirmed complete response (CR) or partial response (PR) per RECIST v1.1. BOR: best response (CR, PR, stable disease \[SD\], progressive disease \[PD\], and not evaluable) among all overall responses recorded from date of randomization of participants or date of first dose of study drug until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study; PD: at least 20% increase in SOD of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Percentage of Participants With Objective Response in Phase 1b
|
—
|
0 Percentage of participants
Interval 0.0 to 45.9
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. DSD was analyzed for participants with SD.
The DSD was defined as the time from the date of first dose of study treatment for Phase 1b until the first date of documented PD (per RECIST v1.1), or death due to any cause, whichever occurred first. PD is at least a 20% increase in sum of diameters of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. Kaplan Meier method was used to evaluate DSD.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=2 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Duration of Stable Disease (DSD) in Phase 1b
|
—
|
5.4 Months
Interval 3.5 to 7.4
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Best percentage change from baseline of the SLD of target lesions per RECIST v1.1 was derived as the biggest decease or the smallest increase from baseline on the SLD among all post-baseline disease assessment including unscheduled assessments. Best percent change is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 1b
|
—
|
17.7 mm
Interval -3.2 to 115.1
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Day 1 up to 16 weeksPopulation: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
The disease control rate at 16 weeks was defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 110 days, following the date of first dose of study drug. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Percentage of Participants With Disease Control at 16 Weeks in Phase 1b
|
—
|
33.3 Percentage of participants
Interval 4.3 to 77.7
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Day 1 up to 24 weeksPopulation: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
The disease control rate at 24 weeks was defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 166 days, following the date of first dose of study drug. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Percentage of Participants With Disease Control at 24 Weeks in Phase 1b
|
—
|
16.7 Percentage of participants
Interval 0.4 to 64.1
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From Day 1 upto 6 monthsPopulation: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
The PFS-6 is the 6-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 6 months. PFS was defined as the time from the date of first dose of study drug for Phase 1b participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Progression Free Survival at 6 Month in Phase 1b
|
—
|
16.7 Percentage of participants
Interval 0.8 to 51.7
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to 90 days after the last dose (approximately 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2
TEAEs
|
22 Participants
|
27 Participants
|
23 Participants
|
12 Participants
|
18 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2
TESAEs
|
15 Participants
|
14 Participants
|
16 Participants
|
10 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Day 1 up to 90 days after the last dose (approximately 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Tri-iodothyronine free decreased
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Anaemia
|
7 Participants
|
9 Participants
|
3 Participants
|
3 Participants
|
4 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Lymphocyte count decreased
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
White blood cell count decreased
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
International normalised ratio increased
|
1 Participants
|
3 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Activated partial thromboplastin time prolonged
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Platelet count decreased
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Blood fibrinogen decreased
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Hepatic function abnormal
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Alanine aminotransferase increased
|
2 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Aspartate aminotransferase increased
|
3 Participants
|
2 Participants
|
2 Participants
|
3 Participants
|
2 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Blood alkaline phosphatase increased
|
2 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Blood bilirubin increased
|
1 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Gamma-glutamyltransferase increased
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Hyperthyroidism
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Hypothyroidism
|
4 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Blood thyroid stimulating hormone increased
|
0 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Thyroxine free decreased
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 up to 90 days after the last dose (approximately 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure \[BP\], pulse rate \[or pulse oximetry at screening\], and respiratory rate). Abnormal physical examinations are defined as any abnormal impact on measurements of height and weight.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Atrial fibrillation
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Bradycardia
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Hypertension
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Hypotension
|
2 Participants
|
6 Participants
|
3 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Hypoxia
|
0 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Pyrexia
|
4 Participants
|
5 Participants
|
7 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Respiratory distress
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Sinus tachycardia
|
0 Participants
|
3 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Tachycardia
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Weight decreased
|
5 Participants
|
3 Participants
|
4 Participants
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Day 1 up to 90 days after the last dose (approximately 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, PR, RR, QRS and QT intervals from the primary lead of the digital 12-lead ECG.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Cardiac failure
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Pericardial effusion
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Cardiac failure congestive
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Atrial tachycardia
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Bradycardia
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Sinus tachycardia
|
0 Participants
|
3 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Angina pectoris
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Ventricular tachycardia
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Tachycardia
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Atrial fibrillation
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
The ECOG scale of performance status describes the level of functioning of participants in terms of their ability to care for themselves, daily activity, and physical ability. ECOG Performance Status Scorings are: 0= fully active, able to carry on all pre-disease performance without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (for example, light house work, office work); 2= ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5= dead. The baseline performance status of participants is presented.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2
ECOG 0
|
11 Participants
|
9 Participants
|
9 Participants
|
4 Participants
|
11 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2
ECOG 1
|
14 Participants
|
18 Participants
|
14 Participants
|
8 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: From Day 1 up to 16 weeksPopulation: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
The disease control rate at 16 weeks was defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 110 days, following the date of randomization for Arm A, B, and C participants and the date of first dose of study drug for Arm D and E participants. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Percentage of Participants With Disease Control at 16 Weeks in Phase 2
|
28.0 Percentage of participants
Interval 12.1 to 49.4
|
18.5 Percentage of participants
Interval 6.3 to 38.1
|
12.5 Percentage of participants
Interval 2.7 to 32.4
|
16.7 Percentage of participants
Interval 2.1 to 48.4
|
21.1 Percentage of participants
Interval 6.1 to 45.6
|
SECONDARY outcome
Timeframe: From Day 1 up to 24 weeksPopulation: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
The disease control rate at 24 weeks was defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 166 days, following the date of randomization for Arm A, B, and C participants and the date of first dose of study drug for Arm D and E participants. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Percentage of Participants With Disease Control at 24 Weeks in Phase 2
|
12.0 Percentage of participants
Interval 2.5 to 31.2
|
11.1 Percentage of participants
Interval 2.4 to 29.2
|
0 Percentage of participants
Interval 0.0 to 14.2
|
16.7 Percentage of participants
Interval 2.1 to 48.4
|
15.8 Percentage of participants
Interval 3.4 to 39.6
|
SECONDARY outcome
Timeframe: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. Participants with OR were analyzed for the specified outcome measure.
The DoR was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression according to RECIST v1.1 that occurred subsequently after response or death due to any cause, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline. Kaplan Meier method was used to evaluate DoR.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=1 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=3 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=1 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=3 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Duration of Response (DoR) in Phase 2
|
7.4 Months
Interval 7.4 to 7.4
|
NA Months
Interval 2.0 to 22.4
Median was not estimable because insufficient number of participants had events.
|
—
|
4.6 Months
Interval 4.6 to 4.6
|
3.1 Months
Interval 1.9 to 7.4
|
SECONDARY outcome
Timeframe: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. Participants with OR were analyzed for the specified outcome measure.
TTR: time from date of randomization of participants for Arm A, B, and C or date of first dose of study drug for Arm D and Arm E until first documented OR per RECIST v1.1. OR: BOR of confirmed CR or PR per RECIST v1.1. BOR: best response (CR, PR, SD, PD, and not evaluable) among all overall responses recorded from date of randomization/date of first dose of study drug until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in SOD of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD; PD: at least 20% increase in SOD of target lesions from smallest sum (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. Kaplan Meier method used to evaluate TTR.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=1 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=3 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=1 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=3 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Time to Response (TTR) in Phase 2
|
7.2 Months
Interval 7.2 to 7.2
|
1.9 Months
Interval 1.9 to 3.7
|
—
|
2.7 Months
Interval 2.7 to 2.7
|
1.8 Months
Interval 1.7 to 1.8
|
SECONDARY outcome
Timeframe: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. DSD was analyzed for participants with SD.
The DSD was defined as the time from the date of randomization for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants until the first date of documented PD (per RECIST v1.1), or death due to any cause, whichever occurred first. PD is at least a 20% increase in sum of diameters of target lesions from smallest sum on study (at least 5 mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. Kaplan Meier method was used to evaluate DSD.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=6 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=4 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=3 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=1 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=1 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Duration of Stable Disease in Phase 2
|
4.2 Months
Interval 3.5 to 7.2
|
3.5 Months
Interval 2.8 to 3.7
|
3.6 Months
Interval 3.5 to 4.3
|
7.7 Months
Interval 7.7 to 7.7
|
3.5 Months
Interval 3.5 to 3.5
|
SECONDARY outcome
Timeframe: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. Participants with any reduction in tumor size were analyzed for the specified outcome measure.
Best percentage change from baseline of the SLD of target lesions per RECIST v1.1 was derived as the biggest decease or the smallest increase from baseline on the SLD among all post-baseline disease assessment including unscheduled assessments. Best percent change is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=21 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=17 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=9 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=17 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2
|
0.00 mm
Interval -58.4 to 116.2
|
8.00 mm
Interval -86.7 to 123.0
|
21.20 mm
Interval -60.0 to 101.2
|
-4.00 mm
Interval -61.1 to 67.2
|
3.00 mm
Interval -100.0 to 54.8
|
SECONDARY outcome
Timeframe: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
The PFS was defined as the time from the date of randomization for Arm A, B, and C participants or the date of first dose of study treatment for Arm D and E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Progression Free Survival in Phase 2
|
1.8 Months
Interval 1.6 to 3.5
|
1.8 Months
Interval 1.6 to 2.8
|
1.6 Months
Interval 1.0 to 1.8
|
1.7 Months
Interval 0.8 to 7.3
|
1.8 Months
Interval 1.6 to 1.9
|
SECONDARY outcome
Timeframe: From Day 1 up to 9 monthsPopulation: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
The PFS-9 is the 9-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 9 months. PFS was defined as the time from the date of first dose of study drug for Arm A, B, C participants or the date of first dose of study drug for Arm D and E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Progression Free Survival at 9 Month (PFS-9) in Phase 2
|
4.2 Percentage of participants
Interval 0.3 to 17.6
|
12.1 Percentage of participants
Interval 3.1 to 27.9
|
NA Percentage of participants
No participants were progression free at 9 months.
|
NA Percentage of participants
No participants were progression free at 9 months.
|
5.3 Percentage of participants
Interval 0.4 to 21.4
|
SECONDARY outcome
Timeframe: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
The OS was defined as the time from date of randomization for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants until death due to any cause. OS was censored at last known alive date. Kaplan Meier method was used to evaluate OS. Kaplan Meier method was used to evaluate OS.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Overall Survival (OS) in Phase 2
|
10.7 Months
Interval 1.0 to 30.7
|
9.2 Months
Interval 1.6 to 32.0
|
3.4 Months
Interval 0.8 to 9.5
|
7.7 Months
Interval 0.8 to 33.8
|
7.0 Months
Interval 0.6 to 18.8
|
SECONDARY outcome
Timeframe: From Day 1 up to 12 monthsPopulation: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
The OS was defined as the time from date of randomization for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants until 12 months. OS was censored at last known alive date. Kaplan Meier method was used to evaluate OS. Kaplan Meier method was used to evaluate OS and 95% confidence interval.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Overall Survival at 12 Months in Phase 2
|
40.7 Percentage of participants
Interval 20.2 to 60.3
|
37.0 Percentage of participants
Interval 19.6 to 54.6
|
NA Percentage of participants
No participants were alive at 12 months.
|
13.1 Percentage of participants
Interval 0.7 to 43.6
|
29.2 Percentage of participants
Interval 10.9 to 50.5
|
SECONDARY outcome
Timeframe: Day 1 through Day 30 post EOT (approximately 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Percentage of participants with OR with positive IFN-γ gene expression is reported. OR: BOR of confirmed CR or PR per RECIST v1.1. BOR: best response (CR, PR, SD, PD, and not evaluable) among all overall responses recorded from date of randomization for Arm A, B, C participants or date of first dose of study drug for Arms D, E participants until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study; PD: at least 20% increase in SOD of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Percentage of Participants With Objective Response With Positive Interferon Gamma (IFN-γ) Gene Expression in Phase 2
|
—
|
15.8 Percenatge of Participants
Interval 3.4 to 39.6
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 through Day 30 post EOT (approximately 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. Only those participants were analyzed who were at risk at 6 months.
Percentage of participants with PFS at 6 month with positive IFN-γ gene expression is reported. The PFS-6 is the 6-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 6 months. PFS was defined as the time from the date of first dose of study drug for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS-6.
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=1 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Percentage of Participants With Progression Free Survival (PFS) at 6 Month With Positive IFN-γ Gene Expression in Phase 2
|
—
|
5.3 Percentage of Participants
Interval 0.4 to 21.4
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 through Day 30 post EOT (approximately 4 years and one month)Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Percentage of participants with objective response in Phase 2 by programmed death-ligand (PD-L1) status is reported. PD-L1 is a protein that may be found on some normal cells and in higher-than-normal amounts on some types of cancer cells. It plays a role in regulating the immune response against some types of cancers and therefore, is the target for some anticancer drugs. PD-L1 status was based on the percentage of tumor cells from baseline tumor tissue samples with PD-L1 membrane staining: PD-L1 high if \>= 1% tumor cells (better response), PD-L1 low/neg if \< 1% tumor cells (low response).
Outcome measures
| Measure |
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 Participants
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=27 Participants
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 Participants
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 Participants
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|
|
Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status
PD-L1 high
|
0 Percentage of participants
Interval 0.0 to 52.2
|
13.3 Percentage of participants
Interval 1.7 to 40.5
|
0 Percentage of participants
Interval 0.0 to 28.5
|
0 Percentage of participants
Interval 0.0 to 41.0
|
33.3 Percentage of participants
Interval 7.5 to 70.1
|
|
Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status
PD-L1 low/negative
|
0 Percentage of participants
Interval 0.0 to 21.8
|
11.1 Percentage of participants
Interval 0.3 to 48.2
|
0 Percentage of participants
Interval 0.0 to 33.6
|
25.0 Percentage of participants
Interval 0.6 to 80.6
|
0 Percentage of participants
Interval 0.0 to 60.2
|
Adverse Events
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Serious events: 2 serious events
Other events: 6 other events
Deaths: 6 deaths
Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Serious events: 14 serious events
Other events: 27 other events
Deaths: 23 deaths
Phase 2 Arm B-M10 mg/kg (Q2W)
Serious events: 16 serious events
Other events: 22 other events
Deaths: 21 deaths
Phase 2 Arm C-T10 mg/kg (Q4W)
Serious events: 10 serious events
Other events: 12 other events
Deaths: 7 deaths
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Serious events: 15 serious events
Other events: 22 other events
Deaths: 21 deaths
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Serious events: 12 serious events
Other events: 18 other events
Deaths: 13 deaths
Serious adverse events
| Measure |
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 participants at risk
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=27 participants at risk
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 participants at risk
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 participants at risk
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 participants at risk
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 participants at risk
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Endocrine disorders
Hypophysitis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
14.8%
4/27 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Gastric perforation
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Obstruction gastric
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Asthenia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Chest discomfort
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Fatigue
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
General physical health deterioration
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Oedema peripheral
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Peripheral swelling
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Pyrexia
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Cellulitis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Enterococcal bacteraemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Enterocolitis infectious
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Pneumonia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Septic shock
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Blood creatinine increased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Glomerular filtration rate decreased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Transaminases increased
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hypophagia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Psychiatric disorders
Hallucination
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Renal and urinary disorders
Renal disorder
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Renal and urinary disorders
Tubulointerstitial nephritis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Apnoea
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Vascular disorders
Embolism
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Vascular disorders
Hypotension
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
Other adverse events
| Measure |
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
n=6 participants at risk
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=27 participants at risk
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm B-M10 mg/kg (Q2W)
n=24 participants at risk
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
|
Phase 2 Arm C-T10 mg/kg (Q4W)
n=12 participants at risk
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).
|
Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=25 participants at risk
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
n=19 participants at risk
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
|
|---|---|---|---|---|---|---|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.0%
4/25 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Eye disorders
Glaucoma
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Blood and lymphatic system disorders
Anaemia
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
33.3%
9/27 • Number of events 16 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.5%
3/24 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
3/12 • Number of events 8 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
32.0%
8/25 • Number of events 13 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
21.1%
4/19 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Blood and lymphatic system disorders
Lymphopenia
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Cardiac disorders
Palpitations
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Cardiac disorders
Pericardial effusion
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Endocrine disorders
Endocrine disorder
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Abdominal discomfort
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.5%
3/24 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
2/6 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
22.2%
6/27 • Number of events 7 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.5%
3/24 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
33.3%
4/12 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
20.0%
5/25 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Aphthous ulcer
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
14.8%
4/27 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
3/12 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.0%
4/25 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Constipation
|
33.3%
2/6 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
33.3%
9/27 • Number of events 10 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
20.8%
5/24 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
33.3%
4/12 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.0%
3/25 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
26.3%
5/19 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
33.3%
9/27 • Number of events 12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.5%
3/24 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
41.7%
5/12 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.0%
4/25 • Number of events 8 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Dry mouth
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Dyspepsia
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
3/12 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 8 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
15.8%
3/19 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 20 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Haematochezia
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Nausea
|
50.0%
3/6 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.9%
7/27 • Number of events 11 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
20.8%
5/24 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
33.3%
4/12 • Number of events 11 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
32.0%
8/25 • Number of events 12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
31.6%
6/19 • Number of events 8 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Oesophageal haemorrhage
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Retching
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 7 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.5%
3/24 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
3/12 • Number of events 8 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
32.0%
8/25 • Number of events 15 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
21.1%
4/19 • Number of events 10 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Asthenia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
6/24 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Chills
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Fatigue
|
50.0%
3/6 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
40.7%
11/27 • Number of events 31 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
6/24 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
41.7%
5/12 • Number of events 14 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
36.0%
9/25 • Number of events 12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
26.3%
5/19 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Gait disturbance
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Influenza like illness
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Localised oedema
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Malaise
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Medical device site pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Oedema
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Oedema peripheral
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
22.2%
6/27 • Number of events 7 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
3/12 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
20.0%
5/25 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
21.1%
4/19 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
General disorders
Pyrexia
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
18.5%
5/27 • Number of events 7 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
6/24 • Number of events 7 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.0%
3/25 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Hepatobiliary disorders
Cholangitis acute
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Ear infection
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Influenza
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Sinusitis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Injury, poisoning and procedural complications
Torus fracture
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Activated partial thromboplastin time prolonged
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Amylase increased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 8 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
3/12 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.0%
3/25 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Bilirubin conjugated increased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Blood albumin decreased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Blood alkaline phosphatase increased
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Blood bilirubin increased
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Blood creatinine increased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Blood fibrinogen decreased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Blood thyroid stimulating hormone increased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Gamma-glutamyltransferase increased
|
33.3%
2/6 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Haemoglobin decreased
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
International normalised ratio increased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 9 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Lipase increased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
15.8%
3/19 • Number of events 8 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 13 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Platelet count decreased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Prothrombin time prolonged
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Tri-iodothyronine free decreased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Weight decreased
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
4/24 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
20.0%
5/25 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
Weight increased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Investigations
White blood cell count decreased
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
37.0%
10/27 • Number of events 28 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
33.3%
8/24 • Number of events 9 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
41.7%
5/12 • Number of events 14 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
36.0%
9/25 • Number of events 15 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
15.8%
3/19 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.9%
7/27 • Number of events 14 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
14.8%
4/27 • Number of events 11 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
3/12 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
20.0%
5/25 • Number of events 10 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
15.8%
3/19 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.5%
3/24 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.5%
3/24 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
15.8%
3/19 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
33.3%
2/6 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
18.5%
5/27 • Number of events 8 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.0%
3/25 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
22.2%
6/27 • Number of events 14 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
3/12 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
24.0%
6/25 • Number of events 11 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 10 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.0%
3/25 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.0%
3/25 • Number of events 7 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Nervous system disorders
Aphonia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Nervous system disorders
Dizziness
|
16.7%
1/6 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
3/12 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Nervous system disorders
Headache
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Nervous system disorders
Lethargy
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Nervous system disorders
Migraine
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Nervous system disorders
Taste disorder
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Psychiatric disorders
Agitation
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Psychiatric disorders
Anxiety
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Psychiatric disorders
Delirium
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Psychiatric disorders
Depressed mood
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.9%
7/27 • Number of events 10 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
3/12 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.0%
3/25 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
10.5%
2/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Renal and urinary disorders
Nephropathy toxic
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Renal and urinary disorders
Urinary retention
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Reproductive system and breast disorders
Genital erosion
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Reproductive system and breast disorders
Testicular pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
22.2%
6/27 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
33.3%
2/6 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
37.0%
10/27 • Number of events 15 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
3/12 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
15.8%
3/19 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.2%
1/24 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
7.4%
2/27 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Lung hyperinflation
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 9 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 21 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
16.7%
1/6 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
16.7%
2/12 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
33.3%
2/6 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
18.5%
5/27 • Number of events 8 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
41.7%
5/12 • Number of events 8 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
24.0%
6/25 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
15.8%
3/19 • Number of events 5 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
14.8%
4/27 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
25.0%
3/12 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
11.1%
3/27 • Number of events 3 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
4.0%
1/25 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Vascular disorders
Hypertension
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
3.7%
1/27 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/12 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.0%
2/25 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Vascular disorders
Hypotension
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
18.5%
5/27 • Number of events 6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
2/24 • Number of events 2 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
12.0%
3/25 • Number of events 4 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
5.3%
1/19 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
|
Vascular disorders
Thrombophlebitis superficial
|
0.00%
0/6 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/27 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/24 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
8.3%
1/12 • Number of events 1 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/25 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
0.00%
0/19 • Day 1 up to 90 days after the last dose (approximately 4 years and one month)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises on going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
- Publication restrictions are in place
Restriction type: OTHER