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A Phase 1b/2 Study of MEDI4736 With Tremelimumab, MEDI4736 or Tremelimumab Monotherapy in Gastric or GEJ Adenocarcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02340975
Recruitment Status : Completed
First Posted : January 19, 2015
Results First Posted : May 11, 2020
Last Update Posted : June 9, 2020
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gastric or Gastroesophageal Junction Adenocarcinoma
Interventions Biological: MEDI4736 + tremelimumab
Biological: MEDI4736
Biological: Tremelimumab
Biological: MEDI4736+tremelimumab
Enrollment 114
Recruitment Details The study was conducted in the United States of America, Japan, Korea, Taiwan and Singapore between 31Mar2015 and 29Apr2019.
Pre-assignment Details A total of 114 participants were randomized in the study, out of which 113 participants received study treatment.
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description 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). 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). 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). 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). 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). 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).
Period Title: Overall Study
Started 6 27 24 12 25 19
Completed 0 0 0 0 0 0
Not Completed 6 27 24 12 25 19
Reason Not Completed
Death             6             23             21             7             21             13
Lost to Follow-up             0             0             0             0             2             0
Withdrawal by Subject             0             0             3             3             2             0
Other             0             4             0             2             0             6
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Total
Hide Arm/Group Description 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). 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). 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). 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). 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). 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 of all reporting groups
Overall Number of Baseline Participants 6 27 24 12 25 19 113
Hide Baseline Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 27 participants 24 participants 12 participants 25 participants 19 participants 113 participants
70.0  (12.7) 60.4  (13.5) 59.8  (12.0) 52.3  (16.0) 58.6  (10.7) 59.9  (12.8) 59.4  (12.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 27 participants 24 participants 12 participants 25 participants 19 participants 113 participants
Female
0
   0.0%
7
  25.9%
5
  20.8%
4
  33.3%
9
  36.0%
5
  26.3%
30
  26.5%
Male
6
 100.0%
20
  74.1%
19
  79.2%
8
  66.7%
16
  64.0%
14
  73.7%
83
  73.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 27 participants 24 participants 12 participants 25 participants 19 participants 113 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
1
   4.2%
0
   0.0%
0
   0.0%
1
   5.3%
2
   1.8%
Not Hispanic or Latino
6
 100.0%
27
 100.0%
23
  95.8%
12
 100.0%
25
 100.0%
18
  94.7%
111
  98.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 27 participants 24 participants 12 participants 25 participants 19 participants 113 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  16.7%
7
  25.9%
11
  45.8%
5
  41.7%
12
  48.0%
13
  68.4%
49
  43.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
5
  83.3%
20
  74.1%
13
  54.2%
6
  50.0%
13
  52.0%
6
  31.6%
63
  55.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
1
   0.9%
1.Primary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 1b
Hide Description 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.
Time Frame Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
6
 100.0%
TESAEs
2
  33.3%
2.Primary Outcome
Title Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1b
Hide Description 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.
Time Frame From first dose of Study drug (Day 1) through 28 days after the administration of MEDI4736 and tremelimumab
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
1
  16.7%
3.Primary Outcome
Title Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
Hide Description 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.
Time Frame Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
Anaemia
1
  16.7%
Lymphopenia
1
  16.7%
Haemoglobin decreased
1
  16.7%
Prothrombin time prolonged
1
  16.7%
Activated partial thromboplastin time prolonged
1
  16.7%
Blood alkaline phosphatase increased
1
  16.7%
Blood bilirubin increased
1
  16.7%
Gamma-glutamyltransferase increased
2
  33.3%
Transaminases increased
1
  16.7%
4.Primary Outcome
Title Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 1b
Hide Description 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.
Time Frame Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
Pyrexia
1
  16.7%
Weight decreased
1
  16.7%
5.Primary Outcome
Title Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 1b
Hide Description 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.
Time Frame Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
1
  16.7%
6.Primary Outcome
Title Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b
Hide Description 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.
Time Frame Baseline (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
ECOG 0
4
  66.7%
ECOG 1
2
  33.3%
7.Primary Outcome
Title Percentage of Participants With Objective Response (OR) in Phase 2
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
11.1
(2.4 to 29.2)
0
(0.0 to 14.2)
8.3
(0.2 to 38.5)
4.0
(0.1 to 20.4)
15.8
(3.4 to 39.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W), Phase 2 Arm B-M10 mg/kg (Q2W)
Comments [Not Specified]
Type of Statistical Test Other
Comments Comparison
Statistical Test of Hypothesis P-Value 0.2376
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 11.1
Confidence Interval (2-Sided) 95%
-0.7 to 23.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W), Phase 2 Arm C-T10 mg/kg (Q4W)
Comments [Not Specified]
Type of Statistical Test Other
Comments Comparison
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-16.8 to 22.4
Estimation Comments [Not Specified]
8.Primary Outcome
Title Progression Free Survival at 6 (PFS-6) Month in Phase 2
Hide Description 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.
Time Frame From Day 1 upto 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
12.1
(3.1 to 27.9)
NA [1] 
(NA to NA)
23.3
(3.6 to 52.9)
12.5
(3.1 to 28.7)
5.3
(0.4 to 21.4)
[1]
No participants were progression free at 6 months.
9.Secondary Outcome
Title Percentage of Participants With Objective Response in Phase 1b
Hide Description 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.
Time Frame 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)
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Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 6
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0
(0.0 to 45.9)
10.Secondary Outcome
Title Duration of Stable Disease (DSD) in Phase 1b
Hide Description 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.
Time Frame 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)
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Hide Analysis Population Description
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.
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 2
Median (Full Range)
Unit of Measure: Months
5.4
(3.5 to 7.4)
11.Secondary Outcome
Title Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 1b
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: mm
17.7
(-3.2 to 115.1)
12.Secondary Outcome
Title Percentage of Participants With Disease Control at 16 Weeks in Phase 1b
Hide Description 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.
Time Frame From Day 1 up to 16 weeks
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Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 6
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
33.3
(4.3 to 77.7)
13.Secondary Outcome
Title Percentage of Participants With Disease Control at 24 Weeks in Phase 1b
Hide Description 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.
Time Frame From Day 1 up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 6
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
16.7
(0.4 to 64.1)
14.Secondary Outcome
Title Progression Free Survival at 6 Month in Phase 1b
Hide Description 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.
Time Frame From Day 1 upto 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
Overall Number of Participants Analyzed 6
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
16.7
(0.8 to 51.7)
15.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2
Hide Description 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.
Time Frame Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
27
 100.0%
23
  95.8%
12
 100.0%
22
  88.0%
18
  94.7%
TESAEs
14
  51.9%
16
  66.7%
10
  83.3%
15
  60.0%
12
  63.2%
16.Secondary Outcome
Title Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Hide Description 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.
Time Frame Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Measure Type: Count of Participants
Unit of Measure: Participants
Anaemia
9
  33.3%
3
  12.5%
3
  25.0%
7
  28.0%
4
  21.1%
Lymphocyte count decreased
1
   3.7%
1
   4.2%
1
   8.3%
0
   0.0%
0
   0.0%
White blood cell count decreased
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
International normalised ratio increased
3
  11.1%
0
   0.0%
1
   8.3%
1
   4.0%
0
   0.0%
Activated partial thromboplastin time prolonged
1
   3.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Platelet count decreased
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
Blood fibrinogen decreased
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.3%
Hepatic function abnormal
0
   0.0%
1
   4.2%
1
   8.3%
0
   0.0%
0
   0.0%
Alanine aminotransferase increased
2
   7.4%
1
   4.2%
2
  16.7%
2
   8.0%
2
  10.5%
Aspartate aminotransferase increased
2
   7.4%
2
   8.3%
3
  25.0%
3
  12.0%
2
  10.5%
Blood alkaline phosphatase increased
0
   0.0%
2
   8.3%
1
   8.3%
2
   8.0%
2
  10.5%
Blood bilirubin increased
0
   0.0%
2
   8.3%
0
   0.0%
1
   4.0%
1
   5.3%
Gamma-glutamyltransferase increased
0
   0.0%
0
   0.0%
0
   0.0%
2
   8.0%
1
   5.3%
Hyperthyroidism
1
   3.7%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
Hypothyroidism
0
   0.0%
0
   0.0%
0
   0.0%
4
  16.0%
0
   0.0%
Blood thyroid stimulating hormone increased
3
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Thyroxine free decreased
1
   3.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Tri-iodothyronine free decreased
2
   7.4%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
17.Secondary Outcome
Title Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Hide Description 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.
Time Frame Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Measure Type: Count of Participants
Unit of Measure: Participants
Atrial fibrillation
1
   3.7%
1
   4.2%
1
   8.3%
0
   0.0%
0
   0.0%
Bradycardia
0
   0.0%
0
   0.0%
1
   8.3%
1
   4.0%
0
   0.0%
Hypertension
1
   3.7%
0
   0.0%
0
   0.0%
1
   4.0%
1
   5.3%
Hypotension
6
  22.2%
3
  12.5%
1
   8.3%
2
   8.0%
1
   5.3%
Hypoxia
2
   7.4%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
Pyrexia
5
  18.5%
7
  29.2%
2
  16.7%
4
  16.0%
2
  10.5%
Respiratory distress
1
   3.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sinus tachycardia
3
  11.1%
1
   4.2%
0
   0.0%
0
   0.0%
0
   0.0%
Tachycardia
1
   3.7%
0
   0.0%
1
   8.3%
1
   4.0%
0
   0.0%
Weight decreased
3
  11.1%
4
  16.7%
1
   8.3%
5
  20.0%
2
  10.5%
18.Secondary Outcome
Title Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Hide Description 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.
Time Frame Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Measure Type: Count of Participants
Unit of Measure: Participants
Sinus tachycardia
3
  11.1%
1
   4.2%
0
   0.0%
0
   0.0%
0
   0.0%
Angina pectoris
1
   3.7%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
Ventricular tachycardia
1
   3.7%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
Tachycardia
1
   3.7%
0
   0.0%
1
   8.3%
1
   4.0%
0
   0.0%
Atrial fibrillation
1
   3.7%
1
   4.2%
1
   8.3%
0
   0.0%
0
   0.0%
Cardiac failure congestive
1
   3.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Atrial tachycardia
0
   0.0%
1
   4.2%
0
   0.0%
0
   0.0%
0
   0.0%
Bradycardia
0
   0.0%
0
   0.0%
1
   8.3%
1
   4.0%
0
   0.0%
Pericardial effusion
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
0
   0.0%
Cardiac failure
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.3%
19.Secondary Outcome
Title Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2
Hide Description 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.
Time Frame Baseline (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Measure Type: Count of Participants
Unit of Measure: Participants
ECOG 0
9
  33.3%
9
  37.5%
4
  33.3%
11
  44.0%
11
  57.9%
ECOG 1
18
  66.7%
14
  58.3%
8
  66.7%
14
  56.0%
8
  42.1%
20.Secondary Outcome
Title Percentage of Participants With Disease Control at 16 Weeks in Phase 2
Hide Description 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.
Time Frame From Day 1 up to 16 weeks
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Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
18.5
(6.3 to 38.1)
12.5
(2.7 to 32.4)
16.7
(2.1 to 48.4)
28.0
(12.1 to 49.4)
21.1
(6.1 to 45.6)
21.Secondary Outcome
Title Percentage of Participants With Disease Control at 24 Weeks in Phase 2
Hide Description 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.
Time Frame From Day 1 up to 24 weeks
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Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
11.1
(2.4 to 29.2)
0
(0.0 to 14.2)
16.7
(2.1 to 48.4)
12.0
(2.5 to 31.2)
15.8
(3.4 to 39.6)
22.Secondary Outcome
Title Duration of Response (DoR) in Phase 2
Hide Description 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.
Time Frame 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)
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Hide Analysis Population Description
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.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 3 0 1 1 3
Median (Full Range)
Unit of Measure: Months
NA [1] 
(2.0 to 22.4)
4.6
(4.6 to 4.6)
7.4
(7.4 to 7.4)
3.1
(1.9 to 7.4)
[1]
Median was not estimable because insufficient number of participants had events.
23.Secondary Outcome
Title Time to Response (TTR) in Phase 2
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 3 0 1 1 3
Median (Full Range)
Unit of Measure: Months
1.9
(1.9 to 3.7)
2.7
(2.7 to 2.7)
7.2
(7.2 to 7.2)
1.8
(1.7 to 1.8)
24.Secondary Outcome
Title Duration of Stable Disease in Phase 2
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 4 3 1 6 1
Median (Full Range)
Unit of Measure: Months
3.5
(2.8 to 3.7)
3.6
(3.5 to 4.3)
7.7
(7.7 to 7.7)
4.2
(3.5 to 7.2)
3.5
(3.5 to 3.5)
25.Secondary Outcome
Title Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2
Hide Description 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.
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 25 17 9 21 17
Median (Full Range)
Unit of Measure: mm
8.00
(-86.7 to 123.0)
21.20
(-60.0 to 101.2)
-4.00
(-61.1 to 67.2)
0.00
(-58.4 to 116.2)
3.00
(-100.0 to 54.8)
26.Secondary Outcome
Title Progression Free Survival in Phase 2
Hide Description 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.
Time Frame 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)
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As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Median (95% Confidence Interval)
Unit of Measure: Months
1.8
(1.6 to 2.8)
1.6
(1.0 to 1.8)
1.7
(0.8 to 7.3)
1.8
(1.6 to 3.5)
1.8
(1.6 to 1.9)
27.Secondary Outcome
Title Progression Free Survival at 9 Month (PFS-9) in Phase 2
Hide Description 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.
Time Frame From Day 1 up to 9 months
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Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
12.1
(3.1 to 27.9)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
4.2
(0.3 to 17.6)
5.3
(0.4 to 21.4)
[1]
No participants were progression free at 9 months.
28.Secondary Outcome
Title Overall Survival (OS) in Phase 2
Hide Description 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.
Time Frame 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)
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Hide Analysis Population Description
As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Median (Full Range)
Unit of Measure: Months
9.2
(1.6 to 32.0)
3.4
(0.8 to 9.5)
7.7
(0.8 to 33.8)
10.7
(1.0 to 30.7)
7.0
(0.6 to 18.8)
29.Secondary Outcome
Title Overall Survival at 12 Months in Phase 2
Hide Description 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.
Time Frame From Day 1 up to 12 months
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As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
37.0
(19.6 to 54.6)
NA [1] 
(NA to NA)
13.1
(0.7 to 43.6)
40.7
(20.2 to 60.3)
29.2
(10.9 to 50.5)
[1]
No participants were alive at 12 months.
30.Secondary Outcome
Title Percentage of Participants With Objective Response With Positive Interferon Gamma (IFN-γ) Gene Expression in Phase 2
Hide Description 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.
Time Frame Day 1 through Day 30 post EOT (approximately 4 years and one month)
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As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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 Number of Participants Analyzed 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percenatge of Participants
15.8
(3.4 to 39.6)
31.Secondary Outcome
Title Percentage of Participants With Progression Free Survival (PFS) at 6 Month With Positive IFN-γ Gene Expression in Phase 2
Hide Description 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.
Time Frame Day 1 through Day 30 post EOT (approximately 4 years and one month)
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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.
Arm/Group Title Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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 Number of Participants Analyzed 1
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
5.3
(0.4 to 21.4)
32.Secondary Outcome
Title Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status
Hide Description 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).
Time Frame Day 1 through Day 30 post EOT (approximately 4 years and one month)
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As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description:
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).
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).
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).
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).
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 Number of Participants Analyzed 27 24 12 25 19
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
PD-L1 high Number Analyzed 15 participants 11 participants 7 participants 5 participants 9 participants
13.3
(1.7 to 40.5)
0
(0.0 to 28.5)
0
(0.0 to 41.0)
0
(0.0 to 52.2)
33.3
(7.5 to 70.1)
PD-L1 low/negative Number Analyzed 9 participants 9 participants 4 participants 15 participants 4 participants
11.1
(0.3 to 48.2)
0
(0.0 to 33.6)
25.0
(0.6 to 80.6)
0
(0.0 to 21.8)
0
(0.0 to 60.2)
Time Frame Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Hide Arm/Group Description 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). 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). 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). 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). 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). 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).
All-Cause Mortality
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)      23/27 (85.19%)      21/24 (87.50%)      7/12 (58.33%)      21/25 (84.00%)      13/19 (68.42%)    
Hide Serious Adverse Events
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/6 (33.33%)      14/27 (51.85%)      16/24 (66.67%)      10/12 (83.33%)      15/25 (60.00%)      12/19 (63.16%)    
Blood and lymphatic system disorders             
Anaemia † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  2
Cardiac disorders             
Cardiac failure congestive † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Sinus tachycardia † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Endocrine disorders             
Adrenal insufficiency † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 1/19 (5.26%)  1
Hypophysitis † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  2 0/19 (0.00%)  0
Gastrointestinal disorders             
Abdominal distension † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 2/24 (8.33%)  2 0/12 (0.00%)  0 2/25 (8.00%)  2 0/19 (0.00%)  0
Abdominal pain † 1  0/6 (0.00%)  0 2/27 (7.41%)  3 1/24 (4.17%)  1 2/12 (16.67%)  3 1/25 (4.00%)  1 2/19 (10.53%)  2
Ascites † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Colitis † 1  0/6 (0.00%)  0 4/27 (14.81%)  4 0/24 (0.00%)  0 2/12 (16.67%)  2 0/25 (0.00%)  0 0/19 (0.00%)  0
Constipation † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Diarrhoea † 1  0/6 (0.00%)  0 2/27 (7.41%)  2 1/24 (4.17%)  1 1/12 (8.33%)  1 2/25 (8.00%)  2 0/19 (0.00%)  0
Dysphagia † 1  0/6 (0.00%)  0 3/27 (11.11%)  3 1/24 (4.17%)  1 1/12 (8.33%)  1 0/25 (0.00%)  0 1/19 (5.26%)  1
Gastric perforation † 1  0/6 (0.00%)  0 1/27 (3.70%)  3 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Gastrointestinal haemorrhage † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Haematemesis † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 1/12 (8.33%)  1 1/25 (4.00%)  2 0/19 (0.00%)  0
Large intestinal obstruction † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 2/25 (8.00%)  3 0/19 (0.00%)  0
Melaena † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Nausea † 1  0/6 (0.00%)  0 2/27 (7.41%)  2 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 1/19 (5.26%)  1
Obstruction gastric † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Pancreatitis † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Upper gastrointestinal haemorrhage † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Vomiting † 1  0/6 (0.00%)  0 2/27 (7.41%)  2 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 2/19 (10.53%)  2
General disorders             
Asthenia † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 1/24 (4.17%)  2 1/12 (8.33%)  1 0/25 (0.00%)  0 1/19 (5.26%)  1
Chest discomfort † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Fatigue † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
General physical health deterioration † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Oedema peripheral † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Peripheral swelling † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Pyrexia † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 2/24 (8.33%)  3 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Hepatobiliary disorders             
Bile duct obstruction † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Hepatic function abnormal † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Jaundice † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Infections and infestations             
Cellulitis † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Enterococcal bacteraemia † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Enterocolitis infectious † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Pneumonia † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 2/24 (8.33%)  2 1/12 (8.33%)  1 1/25 (4.00%)  1 0/19 (0.00%)  0
Septic shock † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Upper respiratory tract infection † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Urinary tract infection † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Injury, poisoning and procedural complications             
Infusion related reaction † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Investigations             
Blood bilirubin increased † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Blood creatinine increased † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Glomerular filtration rate decreased † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Transaminases increased † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Metabolism and nutrition disorders             
Decreased appetite † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 2/24 (8.33%)  2 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  2
Dehydration † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 1/24 (4.17%)  1 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Failure to thrive † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Hyperglycaemia † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Hypoglycaemia † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Hyponatraemia † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Hypophagia † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Bone pain † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Muscular weakness † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Musculoskeletal chest pain † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Malignant pleural effusion † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Squamous cell carcinoma of skin † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Tumour haemorrhage † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Psychiatric disorders             
Hallucination † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Mental status changes † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 2/25 (8.00%)  2 0/19 (0.00%)  0
Renal and urinary disorders             
Acute kidney injury † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 2/19 (10.53%)  2
Haematuria † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Renal disorder † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Tubulointerstitial nephritis † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Urinary tract obstruction † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Apnoea † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Dyspnoea † 1  0/6 (0.00%)  0 2/27 (7.41%)  4 2/24 (8.33%)  2 1/12 (8.33%)  1 1/25 (4.00%)  1 1/19 (5.26%)  1
Hypoxia † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Interstitial lung disease † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  2
Pleural effusion † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 1/12 (8.33%)  1 0/25 (0.00%)  0 1/19 (5.26%)  2
Pneumonitis † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Pneumothorax † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Pulmonary congestion † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Pulmonary embolism † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Respiratory arrest † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Respiratory distress † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Respiratory failure † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Skin and subcutaneous tissue disorders             
Dermatitis acneiform † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Rash maculo-papular † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Vascular disorders             
Deep vein thrombosis † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Embolism † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0 1/25 (4.00%)  1 0/19 (0.00%)  0
Hypotension † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
1
Term from vocabulary, MedDRA
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm B-M10 mg/kg (Q2W) Phase 2 Arm C-T10 mg/kg (Q4W) Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      27/27 (100.00%)      22/24 (91.67%)      12/12 (100.00%)      22/25 (88.00%)      18/19 (94.74%)    
Blood and lymphatic system disorders             
Anaemia † 1  1/6 (16.67%)  1 9/27 (33.33%)  16 3/24 (12.50%)  6 3/12 (25.00%)  8 8/25 (32.00%)  13 4/19 (21.05%)  6
Iron deficiency anaemia † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Lymphopenia † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Cardiac disorders             
Atrial fibrillation † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 1/24 (4.17%)  1 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Bradycardia † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 1/25 (4.00%)  1 0/19 (0.00%)  0
Cardiac failure † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Palpitations † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Pericardial effusion † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Sinus tachycardia † 1  0/6 (0.00%)  0 3/27 (11.11%)  3 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Tachycardia † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 1/12 (8.33%)  1 1/25 (4.00%)  2 0/19 (0.00%)  0
Ventricular tachycardia † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Ear and labyrinth disorders             
Tinnitus † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  2 0/25 (0.00%)  0 0/19 (0.00%)  0
Endocrine disorders             
Endocrine disorder † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Hyperthyroidism † 1  0/6 (0.00%)  0 1/27 (3.70%)  2 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Hypothyroidism † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 4/25 (16.00%)  4 0/19 (0.00%)  0
Eye disorders             
Glaucoma † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Gastrointestinal disorders             
Abdominal discomfort † 1  1/6 (16.67%)  1 3/27 (11.11%)  3 0/24 (0.00%)  0 0/12 (0.00%)  0 2/25 (8.00%)  2 0/19 (0.00%)  0
Abdominal distension † 1  0/6 (0.00%)  0 3/27 (11.11%)  3 3/24 (12.50%)  3 2/12 (16.67%)  2 1/25 (4.00%)  2 0/19 (0.00%)  0
Abdominal pain † 1  2/6 (33.33%)  2 6/27 (22.22%)  7 3/24 (12.50%)  3 4/12 (33.33%)  4 5/25 (20.00%)  5 1/19 (5.26%)  2
Abdominal pain lower † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 2/12 (16.67%)  2 1/25 (4.00%)  2 0/19 (0.00%)  0
Abdominal pain upper † 1  0/6 (0.00%)  0 3/27 (11.11%)  3 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 2/19 (10.53%)  2
Aphthous ulcer † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Ascites † 1  0/6 (0.00%)  0 4/27 (14.81%)  4 0/24 (0.00%)  0 3/12 (25.00%)  3 4/25 (16.00%)  5 1/19 (5.26%)  1
Colitis † 1  0/6 (0.00%)  0 2/27 (7.41%)  2 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Constipation † 1  2/6 (33.33%)  2 9/27 (33.33%)  10 5/24 (20.83%)  6 4/12 (33.33%)  4 3/25 (12.00%)  6 5/19 (26.32%)  5
Diarrhoea † 1  1/6 (16.67%)  1 9/27 (33.33%)  12 3/24 (12.50%)  4 5/12 (41.67%)  6 4/25 (16.00%)  8 2/19 (10.53%)  4
Dry mouth † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 0/24 (0.00%)  0 2/12 (16.67%)  2 1/25 (4.00%)  1 0/19 (0.00%)  0
Dyspepsia † 1  1/6 (16.67%)  1 1/27 (3.70%)  1 1/24 (4.17%)  1 0/12 (0.00%)  0 2/25 (8.00%)  2 0/19 (0.00%)  0
Dysphagia † 1  0/6 (0.00%)  0 1/27 (3.70%)  2 2/24 (8.33%)  2 3/12 (25.00%)  4 2/25 (8.00%)  8 3/19 (15.79%)  4
Gastrooesophageal reflux disease † 1  0/6 (0.00%)  0 2/27 (7.41%)  20 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Haematemesis † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Haematochezia † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Haemorrhoids † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Melaena † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 1/12 (8.33%)  1 1/25 (4.00%)  2 0/19 (0.00%)  0
Nausea † 1  3/6 (50.00%)  3 7/27 (25.93%)  11 5/24 (20.83%)  6 4/12 (33.33%)  11 8/25 (32.00%)  12 6/19 (31.58%)  8
Oesophageal haemorrhage † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Proctalgia † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Retching † 1  0/6 (0.00%)  0 2/27 (7.41%)  3 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Stomatitis † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 1/25 (4.00%)  1 0/19 (0.00%)  0
Vomiting † 1  0/6 (0.00%)  0 3/27 (11.11%)  7 3/24 (12.50%)  3 3/12 (25.00%)  8 8/25 (32.00%)  15 4/19 (21.05%)  10
General disorders             
Asthenia † 1  0/6 (0.00%)  0 2/27 (7.41%)  5 6/24 (25.00%)  6 0/12 (0.00%)  0 2/25 (8.00%)  2 1/19 (5.26%)  1
Chills † 1  1/6 (16.67%)  1 1/27 (3.70%)  1 1/24 (4.17%)  1 1/12 (8.33%)  1 2/25 (8.00%)  2 0/19 (0.00%)  0
Fatigue † 1  3/6 (50.00%)  3 11/27 (40.74%)  31 6/24 (25.00%)  6 5/12 (41.67%)  14 9/25 (36.00%)  12 5/19 (26.32%)  6
Gait disturbance † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 1/24 (4.17%)  1 1/12 (8.33%)  1 1/25 (4.00%)  1 0/19 (0.00%)  0
Influenza like illness † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 2/19 (10.53%)  2
Localised oedema † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Malaise † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 1/19 (5.26%)  1
Medical device site pain † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Non-cardiac chest pain † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  1 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Oedema † 1  1/6 (16.67%)  1 1/27 (3.70%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Oedema peripheral † 1  0/6 (0.00%)  0 6/27 (22.22%)  7 1/24 (4.17%)  1 3/12 (25.00%)  5 5/25 (20.00%)  6 4/19 (21.05%)  4
Pain † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 1/24 (4.17%)  1 0/12 (0.00%)  0 1/25 (4.00%)  1 1/19 (5.26%)  1
Pyrexia † 1  1/6 (16.67%)  1 5/27 (18.52%)  7 6/24 (25.00%)  7 2/12 (16.67%)  5 3/25 (12.00%)  6 2/19 (10.53%)  3
Hepatobiliary disorders             
Cholangitis acute † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Infections and infestations             
Conjunctivitis † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 2/25 (8.00%)  2 1/19 (5.26%)  1
Ear infection † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Influenza † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Sinusitis † 1  0/6 (0.00%)  0 2/27 (7.41%)  2 1/24 (4.17%)  1 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Upper respiratory tract infection † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 1/25 (4.00%)  1 1/19 (5.26%)  2
Urinary tract infection † 1  0/6 (0.00%)  0 1/27 (3.70%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Injury, poisoning and procedural complications             
Fall † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Skin abrasion † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Torus fracture † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Investigations             
Activated partial thromboplastin time prolonged † 1  1/6 (16.67%)  1 1/27 (3.70%)  2 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Alanine aminotransferase increased † 1  0/6 (0.00%)  0 2/27 (7.41%)  2 1/24 (4.17%)  5 2/12 (16.67%)  3 2/25 (8.00%)  2 2/19 (10.53%)  2
Amylase increased † 1  0/6 (0.00%)  0 1/27 (3.70%)  3 0/24 (0.00%)  0 2/12 (16.67%)  2 2/25 (8.00%)  2 2/19 (10.53%)  3
Aspartate aminotransferase increased † 1  0/6 (0.00%)  0 2/27 (7.41%)  4 2/24 (8.33%)  8 3/12 (25.00%)  5 3/25 (12.00%)  3 2/19 (10.53%)  2
Bilirubin conjugated increased † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Blood albumin decreased † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 2/12 (16.67%)  2 0/25 (0.00%)  0 0/19 (0.00%)  0
Blood alkaline phosphatase increased † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 2/24 (8.33%)  2 1/12 (8.33%)  1 2/25 (8.00%)  3 2/19 (10.53%)  3
Blood bilirubin increased † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 2/24 (8.33%)  4 0/12 (0.00%)  0 1/25 (4.00%)  2 0/19 (0.00%)  0
Blood creatinine increased † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 1/24 (4.17%)  2 0/12 (0.00%)  0 1/25 (4.00%)  1 1/19 (5.26%)  2
Blood fibrinogen decreased † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  1
Blood thyroid stimulating hormone increased † 1  0/6 (0.00%)  0 3/27 (11.11%)  3 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Gamma-glutamyltransferase increased † 1  2/6 (33.33%)  3 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 2/25 (8.00%)  2 1/19 (5.26%)  1
Haemoglobin decreased † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
International normalised ratio increased † 1  0/6 (0.00%)  0 3/27 (11.11%)  9 0/24 (0.00%)  0 1/12 (8.33%)  2 1/25 (4.00%)  2 0/19 (0.00%)  0
Lipase increased † 1  0/6 (0.00%)  0 1/27 (3.70%)  3 1/24 (4.17%)  1 2/12 (16.67%)  3 1/25 (4.00%)  1 3/19 (15.79%)  8
Lymphocyte count decreased † 1  0/6 (0.00%)  0 1/27 (3.70%)  13 1/24 (4.17%)  1 1/12 (8.33%)  2 0/25 (0.00%)  0 0/19 (0.00%)  0
Platelet count decreased † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  2 0/25 (0.00%)  0 0/19 (0.00%)  0
Prothrombin time prolonged † 1  1/6 (16.67%)  1 0/27 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Tri-iodothyronine free decreased † 1  0/6 (0.00%)  0 2/27 (7.41%)  3 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 0/19 (0.00%)  0
Weight decreased † 1  1/6 (16.67%)  1 3/27 (11.11%)  3 4/24 (16.67%)  4 1/12 (8.33%)  1 5/25 (20.00%)  5 2/19 (10.53%)  3
Weight increased † 1  0/6 (0.00%)  0 1/27 (3.70%)  2 0/24 (0.00%)  0 0/12 (0.00%)  0 0/25 (0.00%)  0 1/19 (5.26%)  2
White blood cell count decreased † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1 0/25 (0.00%)  0 0/19 (0.00%)  0
Metabolism and nutrition disorders             
Decreased appetite † 1  0/6 (0.00%)  0 10/27 (37.04%)  28 8/24 (33.33%)  9 5/12 (41.67%)  14 9/25 (36.00%)  15 3/19 (15.79%)  5
Dehydration † 1  0/6 (0.00%)  0 3/27 (11.11%)  4 2/24 (8.33%)  2 1/12 (8.33%)  1 1/25 (4.00%)  1 0/19 (0.00%)  0
Hyperglycaemia † 1  0/6 (0.00%)  0 7/27 (25.93%)  14 1/24 (4.17%)  3 0/12 (0.00%)  0 1/25 (4.00%)  2 1/19 (5.26%)  2
Hyperkalaemia † 1  0/6 (0.00%)  0 0/27 (0.00%)  0 2/24 (8.33%)  2 0/12 (0.00%)  0 1/25 (4.00%)  1