- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02340975
A Phase 1b/2 Study of MEDI4736 With Tremelimumab, MEDI4736 or Tremelimumab Monotherapy in Gastric or GEJ Adenocarcinoma
June 2, 2020 updated by: MedImmune LLC
A Phase 1b/2 Study of MEDI4736 in Combination With Tremelimumab, MEDI4736 Monotherapy, and Tremelimumab Monotherapy in Subjects With Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma
This is a randomized, multicenter, open-label, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, PK, pharmacodynamics, and immunogenicity of MEDI4736 in combination with tremelimumab, MEDI4736 monotherapy or tremelimumab monotherapy in participants with metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
114
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Quebec
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Montreal, Quebec, Canada, H4A 3J1
- Research Site
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Kawasaki-shi, Japan, 216-8511
- Research Site
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Koto-ku, Japan, 135-8550
- Research Site
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Osaka-shi, Japan, 541-8567
- Research Site
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Seongnam-si, Korea, Republic of, 13620
- Research Site
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Seoul, Korea, Republic of, 03722
- Research Site
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Seoul, Korea, Republic of, 03080
- Research Site
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Seoul, Korea, Republic of, 06351
- Research Site
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Singapore, Singapore, 308433
- Research Site
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Singapore, Singapore, 119082
- Research Site
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Taipei, Taiwan, 100
- Research Site
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Taipei, Taiwan, 11217
- Research Site
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Taoyuan, Taiwan, 333
- Research Site
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California
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Los Angeles, California, United States, 90033
- Research Site
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Santa Monica, California, United States, 90404
- Research Site
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Connecticut
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New Haven, Connecticut, United States, 06520
- Research Site
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Florida
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Tampa, Florida, United States, 33612
- Research Site
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Illinois
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Chicago, Illinois, United States, 60637
- Research Site
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Maryland
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Baltimore, Maryland, United States, 21231
- Research Site
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New York
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New York, New York, United States, 10032
- Research Site
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New York, New York, United States, 10065
- Research Site
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New York, New York, United States, 10116
- Research Site
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Ohio
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Cleveland, Ohio, United States, 44106
- Research Site
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Oregon
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Portland, Oregon, United States, 97213
- Research Site
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19111
- Research Site
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South Carolina
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Greenville, South Carolina, United States, 29605
- Research Site
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Tennessee
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Nashville, Tennessee, United States, 37203
- Research Site
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Texas
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Houston, Texas, United States, 77030
- Research Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 99 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male and female participants
- 18 years and older
- Histological or cytological confirmation of metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma
- Participants must have received and have progressed, or are refractory to standard regimens
- Participants must have at least one lesion amenable to biospy
Exclusion Criteria:
- Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
- Previous immunotherapy
- Concurrent or prior use of immunosuppressive medication with 14 days
- Active or prior documented autoimmune or inflammatory disease within 3 years with some exceptions
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)
Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma will receive 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, participants will receive MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
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MEDI4736 will be administered by IV infusion in combination with tremelimumab.
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Experimental: Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma will receive 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, participants will receive MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
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MEDI4736 will be administered by IV infusion in combination with tremelimumab.
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Experimental: Phase 2 Arm B-M10 mg/kg (Q2W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma will receive IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).
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MEDI4736 will be administered by IV infusion.
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Experimental: Phase 2 Arm C-T10 mg/kg (Q4W)
Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma will receive 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).
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Tremelimumab will be administered by IV infusion.
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Experimental: Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma will receive 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, participants will receive MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
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MEDI4736 will be administered by IV infusion in combination with tremelimumab.
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Experimental: Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)
Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature will receive 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, participants will receive MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).
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MEDI4736 will be administered by IV infusion in combination with tremelimumab.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 1b
Time Frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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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.
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Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1b
Time Frame: From first dose of Study drug (Day 1) through 28 days after the administration of MEDI4736 and tremelimumab
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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.
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From first dose of Study drug (Day 1) through 28 days after the administration of MEDI4736 and tremelimumab
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Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
Time Frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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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.
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Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 1b
Time Frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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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.
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Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 1b
Time Frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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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.
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Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b
Time Frame: Baseline (Day 1)
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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.
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Baseline (Day 1)
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Percentage of Participants With Objective Response (OR) in Phase 2
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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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.
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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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Progression Free Survival at 6 (PFS-6) Month in Phase 2
Time Frame: From Day 1 upto 6 months
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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.
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From Day 1 upto 6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of Participants With Objective Response in Phase 1b
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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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.
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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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Duration of Stable Disease (DSD) in Phase 1b
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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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.
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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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Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 1b
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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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.
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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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Percentage of Participants With Disease Control at 16 Weeks in Phase 1b
Time Frame: From Day 1 up to 16 weeks
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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.
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From Day 1 up to 16 weeks
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Percentage of Participants With Disease Control at 24 Weeks in Phase 1b
Time Frame: From Day 1 up to 24 weeks
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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.
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From Day 1 up to 24 weeks
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Progression Free Survival at 6 Month in Phase 1b
Time Frame: From Day 1 upto 6 months
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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.
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From Day 1 upto 6 months
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Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2
Time Frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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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.
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Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Time Frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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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.
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Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Time Frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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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.
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Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Time Frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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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.
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Day 1 up to 90 days after the last dose (approximately 4 years and one month)
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Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2
Time Frame: Baseline (Day 1)
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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.
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Baseline (Day 1)
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Percentage of Participants With Disease Control at 16 Weeks in Phase 2
Time Frame: From Day 1 up to 16 weeks
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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.
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From Day 1 up to 16 weeks
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Percentage of Participants With Disease Control at 24 Weeks in Phase 2
Time Frame: From Day 1 up to 24 weeks
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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.
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From Day 1 up to 24 weeks
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Duration of Response (DoR) in Phase 2
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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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.
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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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Time to Response (TTR) in Phase 2
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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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.
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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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Duration of Stable Disease in Phase 2
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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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.
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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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Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2
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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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.
|
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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Progression Free Survival in Phase 2
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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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.
|
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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Progression Free Survival at 9 Month (PFS-9) in Phase 2
Time Frame: From Day 1 up to 9 months
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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.
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From Day 1 up to 9 months
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Overall Survival (OS) in Phase 2
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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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.
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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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Overall Survival at 12 Months in Phase 2
Time Frame: From Day 1 up to 12 months
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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.
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From Day 1 up to 12 months
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Percentage of Participants With Objective Response With Positive Interferon Gamma (IFN-γ) Gene Expression in Phase 2
Time Frame: Day 1 through Day 30 post EOT (approximately 4 years and one month)
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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.
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Day 1 through Day 30 post EOT (approximately 4 years and one month)
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Percentage of Participants With Progression Free Survival (PFS) at 6 Month With Positive IFN-γ Gene Expression in Phase 2
Time Frame: Day 1 through Day 30 post EOT (approximately 4 years and one month)
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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.
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Day 1 through Day 30 post EOT (approximately 4 years and one month)
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Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status
Time Frame: Day 1 through Day 30 post EOT (approximately 4 years and one month)
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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).
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Day 1 through Day 30 post EOT (approximately 4 years and one month)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: MedImmune, LLC MedImmune, LLC, MedImmune LLC
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 31, 2015
Primary Completion (Actual)
April 29, 2019
Study Completion (Actual)
April 29, 2019
Study Registration Dates
First Submitted
January 14, 2015
First Submitted That Met QC Criteria
January 14, 2015
First Posted (Estimate)
January 19, 2015
Study Record Updates
Last Update Posted (Actual)
June 9, 2020
Last Update Submitted That Met QC Criteria
June 2, 2020
Last Verified
May 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Adenocarcinoma
- Esophageal Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Durvalumab
- Tremelimumab
- Antibodies, Monoclonal
Other Study ID Numbers
- D4190C00021
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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