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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

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Gastric or Gastroesophageal Junction Adenocarcinoma Biological: MEDI4736 + tremelimumab Biological: MEDI4736 Biological: Tremelimumab Biological: MEDI4736+tremelimumab Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 114 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 31, 2015
Actual Primary Completion Date : April 29, 2019
Actual Study Completion Date : April 29, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
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).
Biological: MEDI4736 + tremelimumab
MEDI4736 will be administered by IV infusion in combination with tremelimumab.

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).
Biological: MEDI4736 + tremelimumab
MEDI4736 will be administered by IV infusion in combination with tremelimumab.

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).
Biological: MEDI4736
MEDI4736 will be administered by IV infusion.

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).
Biological: Tremelimumab
Tremelimumab will be administered by IV infusion.

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).
Biological: MEDI4736+tremelimumab
MEDI4736 will be administered by IV infusion in combination with tremelimumab.

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).
Biological: MEDI4736 + tremelimumab
MEDI4736 will be administered by IV infusion in combination with tremelimumab.




Primary Outcome Measures :
  1. 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) ]
    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.

  2. 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 ]
    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.

  3. 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) ]
    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.

  4. 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) ]
    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.

  5. 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) ]
    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.

  6. Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b [ Time Frame: Baseline (Day 1) ]
    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.

  7. 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) ]
    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.

  8. Progression Free Survival at 6 (PFS-6) Month in Phase 2 [ Time Frame: From Day 1 upto 6 months ]
    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.


Secondary Outcome Measures :
  1. 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) ]
    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.

  2. 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) ]
    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.

  3. 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) ]
    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.

  4. Percentage of Participants With Disease Control at 16 Weeks in Phase 1b [ Time Frame: From Day 1 up to 16 weeks ]
    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.

  5. Percentage of Participants With Disease Control at 24 Weeks in Phase 1b [ Time Frame: From Day 1 up to 24 weeks ]
    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.

  6. Progression Free Survival at 6 Month in Phase 1b [ Time Frame: From Day 1 upto 6 months ]
    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.

  7. 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) ]
    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.

  8. 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) ]
    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.

  9. 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) ]
    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.

  10. 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) ]
    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.

  11. Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2 [ Time Frame: Baseline (Day 1) ]
    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.

  12. Percentage of Participants With Disease Control at 16 Weeks in Phase 2 [ Time Frame: From Day 1 up to 16 weeks ]
    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.

  13. Percentage of Participants With Disease Control at 24 Weeks in Phase 2 [ Time Frame: From Day 1 up to 24 weeks ]
    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.

  14. 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) ]
    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.

  15. 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) ]
    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.

  16. 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) ]
    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.

  17. 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) ]
    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.

  18. 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) ]
    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.

  19. Progression Free Survival at 9 Month (PFS-9) in Phase 2 [ Time Frame: From Day 1 up to 9 months ]
    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.

  20. 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) ]
    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.

  21. Overall Survival at 12 Months in Phase 2 [ Time Frame: From Day 1 up to 12 months ]
    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.

  22. 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) ]
    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.

  23. 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) ]
    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.

  24. 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) ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female participants
  2. 18 years and older
  3. Histological or cytological confirmation of metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma
  4. Participants must have received and have progressed, or are refractory to standard regimens
  5. Participants must have at least one lesion amenable to biospy

Exclusion Criteria:

  1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
  2. Previous immunotherapy
  3. Concurrent or prior use of immunosuppressive medication with 14 days
  4. Active or prior documented autoimmune or inflammatory disease within 3 years with some exceptions

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02340975


Locations
Layout table for location information
United States, California
Research Site
Los Angeles, California, United States, 90033
Research Site
Santa Monica, California, United States, 90404
United States, Connecticut
Research Site
New Haven, Connecticut, United States, 06520
United States, Florida
Research Site
Tampa, Florida, United States, 33612
United States, Illinois
Research Site
Chicago, Illinois, United States, 60637
United States, Maryland
Research Site
Baltimore, Maryland, United States, 21231
United States, New York
Research Site
New York, New York, United States, 10032
Research Site
New York, New York, United States, 10065
Research Site
New York, New York, United States, 10116
United States, Ohio
Research Site
Cleveland, Ohio, United States, 44106
United States, Oregon
Research Site
Portland, Oregon, United States, 97213
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States, 19111
United States, South Carolina
Research Site
Greenville, South Carolina, United States, 29605
United States, Tennessee
Research Site
Nashville, Tennessee, United States, 37203
United States, Texas
Research Site
Houston, Texas, United States, 77030
Canada, Quebec
Research Site
Montreal, Quebec, Canada, H4A 3J1
Japan
Research Site
Kawasaki-shi, Japan, 216-8511
Research Site
Koto-ku, Japan, 135-8550
Research Site
Osaka-shi, Japan, 541-8567
Korea, Republic of
Research Site
Seongnam-si, Korea, Republic of, 13620
Research Site
Seoul, Korea, Republic of, 03080
Research Site
Seoul, Korea, Republic of, 03722
Research Site
Seoul, Korea, Republic of, 06351
Singapore
Research Site
Singapore, Singapore, 119082
Research Site
Singapore, Singapore, 308433
Taiwan
Research Site
Taipei, Taiwan, 100
Research Site
Taipei, Taiwan, 11217
Research Site
Taoyuan, Taiwan, 333
Sponsors and Collaborators
MedImmune LLC
Investigators
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Study Director: MedImmune, LLC MedImmune, LLC MedImmune LLC
  Study Documents (Full-Text)

Documents provided by MedImmune LLC:
Study Protocol  [PDF] January 24, 2017
Statistical Analysis Plan  [PDF] May 15, 2019

Additional Information:
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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02340975    
Other Study ID Numbers: D4190C00021
First Posted: January 19, 2015    Key Record Dates
Results First Posted: May 11, 2020
Last Update Posted: June 9, 2020
Last Verified: May 2020
Keywords provided by MedImmune LLC:
Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Immunotherapy
Antibodies, Monoclonal
Tremelimumab
MEDI4736
Additional relevant MeSH terms:
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Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Durvalumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs