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

Primary Purpose

Gastric or Gastroesophageal Junction Adenocarcinoma

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

MEDI4736 + tremelimumab

MEDI4736

Tremelimumab

MEDI4736+tremelimumab

MEDI4736 + tremelimumab

About this trial

This is an interventional treatment trial for Gastric or Gastroesophageal Junction Adenocarcinoma focused on measuring Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Immunotherapy, Antibodies, Monoclonal, Tremelimumab, MEDI4736

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

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)

Arm Description

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).

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).

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).

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).

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).

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).

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 1b

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.

Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1b

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.

Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b

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.

Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 1b

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.

Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 1b

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.

Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b

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.

Percentage of Participants With Objective Response (OR) in Phase 2

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.

Progression Free Survival at 6 (PFS-6) Month in Phase 2

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

Percentage of Participants With Objective Response in Phase 1b

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.

Duration of Stable Disease (DSD) in Phase 1b

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.

Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 1b

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.

Percentage of Participants With Disease Control at 16 Weeks in Phase 1b

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.

Percentage of Participants With Disease Control at 24 Weeks in Phase 1b

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.

Progression Free Survival at 6 Month in Phase 1b

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.

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2

Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2

Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2

Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2

Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2

Percentage of Participants With Disease Control at 16 Weeks in Phase 2

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.

Percentage of Participants With Disease Control at 24 Weeks in Phase 2

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.

Duration of Response (DoR) in Phase 2

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 to Response (TTR) in Phase 2

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.

Duration of Stable Disease in Phase 2

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.

Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2

Progression Free Survival in Phase 2

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.

Progression Free Survival at 9 Month (PFS-9) in Phase 2

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.

Overall Survival (OS) in Phase 2

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.

Overall Survival at 12 Months in Phase 2

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.

Percentage of Participants With Objective Response With Positive Interferon Gamma (IFN-γ) Gene Expression in Phase 2

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.

Percentage of Participants With Progression Free Survival (PFS) at 6 Month With Positive IFN-γ Gene Expression in Phase 2

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.

Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status

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).

Full Information

NCT ID

NCT02340975

First Posted

January 14, 2015

Last Updated

June 2, 2020

Sponsor

MedImmune LLC

1. Study Identification

Unique Protocol Identification Number

NCT02340975

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Completed

Study Start Date

March 31, 2015 (Actual)

Primary Completion Date

April 29, 2019 (Actual)

Study Completion Date

April 29, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MedImmune LLC

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastric or Gastroesophageal Junction Adenocarcinoma

Keywords

Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Immunotherapy, Antibodies, Monoclonal, Tremelimumab, MEDI4736

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

114 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)

Arm Type

Experimental

Arm Description

Arm Title

Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)

Arm Type

Experimental

Arm Description

Arm Title

Phase 2 Arm B-M10 mg/kg (Q2W)

Arm Type

Experimental

Arm Description

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).

Arm Title

Phase 2 Arm C-T10 mg/kg (Q4W)

Arm Type

Experimental

Arm Description

Arm Title

Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)

Arm Type

Experimental

Arm Description

Arm Title

Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

MEDI4736 + tremelimumab

Intervention Description

MEDI4736 will be administered by IV infusion in combination with tremelimumab.

Intervention Type

Biological

Intervention Name(s)

MEDI4736 + tremelimumab

Intervention Description

MEDI4736 will be administered by IV infusion in combination with tremelimumab.

Intervention Type

Biological

Intervention Name(s)

MEDI4736

Intervention Description

MEDI4736 will be administered by IV infusion.

Intervention Type

Biological

Intervention Name(s)

Tremelimumab

Intervention Description

Tremelimumab will be administered by IV infusion.

Intervention Type

Biological

Intervention Name(s)

MEDI4736+tremelimumab

Intervention Description

MEDI4736 will be administered by IV infusion in combination with tremelimumab.

Intervention Type

Biological

Intervention Name(s)

MEDI4736 + tremelimumab

Intervention Description

MEDI4736 will be administered by IV infusion in combination with tremelimumab.

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 1b

Description

Time Frame

Day 1 up to 90 days after the last dose (approximately 4 years and one month)

Title

Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1b

Description

Time Frame

From first dose of Study drug (Day 1) through 28 days after the administration of MEDI4736 and tremelimumab

Title

Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b

Description

Time Frame

Day 1 up to 90 days after the last dose (approximately 4 years and one month)

Title

Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 1b

Description

Time Frame

Day 1 up to 90 days after the last dose (approximately 4 years and one month)

Title

Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 1b

Description

Time Frame

Day 1 up to 90 days after the last dose (approximately 4 years and one month)

Title

Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b

Description

Time Frame

Baseline (Day 1)

Title

Percentage of Participants With Objective Response (OR) in Phase 2

Description

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)

Title

Progression Free Survival at 6 (PFS-6) Month in Phase 2

Description

Time Frame

From Day 1 upto 6 months

Secondary Outcome Measure Information:

Title

Percentage of Participants With Objective Response in Phase 1b

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

Title

Duration of Stable Disease (DSD) in Phase 1b

Description

Time Frame

Title

Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 1b

Description

Time Frame

Title

Percentage of Participants With Disease Control at 16 Weeks in Phase 1b

Description

Time Frame

From Day 1 up to 16 weeks

Title

Percentage of Participants With Disease Control at 24 Weeks in Phase 1b

Description

Time Frame

From Day 1 up to 24 weeks

Title

Progression Free Survival at 6 Month in Phase 1b

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

Title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2

Description

Time Frame

Day 1 up to 90 days after the last dose (approximately 4 years and one month)

Title

Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2

Description

Time Frame

Day 1 up to 90 days after the last dose (approximately 4 years and one month)

Title

Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2

Description

Time Frame

Day 1 up to 90 days after the last dose (approximately 4 years and one month)

Title

Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2

Description

Time Frame

Day 1 up to 90 days after the last dose (approximately 4 years and one month)

Title

Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2

Description

Time Frame

Baseline (Day 1)

Title

Percentage of Participants With Disease Control at 16 Weeks in Phase 2

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

Title

Percentage of Participants With Disease Control at 24 Weeks in Phase 2

Description

Time Frame

From Day 1 up to 24 weeks

Title

Duration of Response (DoR) in Phase 2

Description

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)

Title

Time to Response (TTR) in Phase 2

Description

Time Frame

Title

Duration of Stable Disease in Phase 2

Description

Time Frame

Title

Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2

Description

Time Frame

Title

Progression Free Survival in Phase 2

Description

Time Frame

Title

Progression Free Survival at 9 Month (PFS-9) in Phase 2

Description

Time Frame

From Day 1 up to 9 months

Title

Overall Survival (OS) in Phase 2

Description

Time Frame

Title

Overall Survival at 12 Months in Phase 2

Description

Time Frame

From Day 1 up to 12 months

Title

Percentage of Participants With Objective Response With Positive Interferon Gamma (IFN-γ) Gene Expression in Phase 2

Description

Time Frame

Day 1 through Day 30 post EOT (approximately 4 years and one month)

Title

Percentage of Participants With Progression Free Survival (PFS) at 6 Month With Positive IFN-γ Gene Expression in Phase 2

Description

Time Frame

Day 1 through Day 30 post EOT (approximately 4 years and one month)

Title

Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status

Description

Time Frame

Day 1 through Day 30 post EOT (approximately 4 years and one month)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

MedImmune, LLC MedImmune, LLC

Organizational Affiliation

MedImmune LLC

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90033

Country

United States

Facility Name

Research Site

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

Research Site

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Facility Name

Research Site

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

Research Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

Research Site

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21231

Country

United States

Facility Name

Research Site

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Research Site

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Research Site

City

New York

State/Province

New York

ZIP/Postal Code

10116

Country

United States

Facility Name

Research Site

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

Facility Name

Research Site

City

Portland

State/Province

Oregon

ZIP/Postal Code

97213

Country

United States

Facility Name

Research Site

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19111

Country

United States

Facility Name

Research Site

City

Greenville

State/Province

South Carolina

ZIP/Postal Code

29605

Country

United States

Facility Name

Research Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Research Site

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Research Site

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H4A 3J1

Country

Canada

Facility Name

Research Site

City

Kawasaki-shi

ZIP/Postal Code

216-8511

Country

Japan

Facility Name

Research Site

City

Koto-ku

ZIP/Postal Code

135-8550

Country

Japan

Facility Name

Research Site

City

Osaka-shi

ZIP/Postal Code

541-8567

Country

Japan

Facility Name

Research Site

City

Seongnam-si

ZIP/Postal Code

13620

Country

Korea, Republic of

Facility Name

Research Site

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

Facility Name

Research Site

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

Facility Name

Research Site

City

Seoul

ZIP/Postal Code

06351

Country

Korea, Republic of

Facility Name

Research Site

City

Singapore

ZIP/Postal Code

119082

Country

Singapore

Facility Name

Research Site

City

Singapore

ZIP/Postal Code

308433

Country

Singapore

Facility Name

Research Site

City

Taipei

ZIP/Postal Code

100

Country

Taiwan

Facility Name

Research Site

City

Taipei

ZIP/Postal Code

11217

Country

Taiwan

Facility Name

Research Site

City

Taoyuan

ZIP/Postal Code

333

Country

Taiwan

12. IPD Sharing Statement

Links:

URL

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D4190C00021&attachmentIdentifier=55b427f9-1d33-4bb5-871e-556d7cad26eb&fileName=Redacted_D4190C00021_SAP_v3.0_final.pdf&versionIdentifier=

Description

Redacted D4190C00021 SAP v3.0 final

URL

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D4190C00021&attachmentIdentifier=97082c09-4d33-45f5-a36f-d61451f3915e&fileName=Protocol_D4190C00021_Redacted_Final_April2020_Redacted.pdf&versionIdentifier=

Description

Protocol D4190C00021_Redacted_Final_April2020_Redacted

Learn more about this trial

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

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

Gastric or Gastroesophageal Junction Adenocarcinoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial