Locally Advanced (Unresectable) or Metastatic Adenocarcinoma of the Gastric and Gastro-esophageal Junction
Conditions
Brief summary
The purpose of the study is to compare the efficacy of Ipilimumab and standard of care as sequential or maintenance treatment immediately after first-line chemotherapy in the treatment of unresectable or metastatic gastric and gastro-esophageal cancer.
Interventions
BIOLOGICALIpilimumab
OTHERBest Supportive care (BSC)
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Key Inclusion Criteria: * Histologically confirmed, unresectable locally advanced or metastatic adenocarcinoma of the gastric and gastro-esophageal junction * Received first-line chemotherapy using fluoropyrimidine and platinum combination without disease progression * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Measurable disease by modified WHO criteria (unless complete response from previous chemotherapy) Key
Exclusion criteria
* Known Human Epidermal growth factor Receptor2 (HER2) positive status * Radiological evidence of brain metastases * History of severe autoimmune or immune mediated disease requiring prolonged immunosuppressive treatment * Inadequate hematologic, renal and hepatic function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immune-related Progression Free Survival (irPFS) as Per Assessment of a Blinded Independent Review Committee (IRC) According to Immune Related Response Criteria (irRC) Guidelines | Randomization up to 91 irPFS events (Approximately 19 months ) | irPFS is defined as the time between the randomization date and the time of disease progression per irRC or death, whichever occurs first. irRC criteria=Measurable new lesions: incorporated into the tumor burden (eg, added to the index lesions); do not define progression unless the total measurable tumor burden increases by the required amount (25%). New non-measurable lesions: not considered progression if the total measurable tumor burden is stable or shrinking. irPFS was measured in months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Per Modified World Health Organization (mWHO) Criteria | Randomization up to 91 irPFS events (Approximately 19 months ) | PFS per mWHO was defined as the time between the randomization date and the time of disease progression per mWHO criteria or death, whichever occurred first and was measured in months. mWHO criteria: New lesions always mean progression; Changes in non-measurable lesions contribute in the definitions of Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD). |
| Overall Survival (OS) at Primary Endpoint | Randomization up to 91 irPFS events (Approximately 19 months) | OS was defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored on the last date the participant was known to be alive. |
| Overall Survival (OS) at Study Completion | Randomization up to end of study, April 2015 (Approximately 28 months) | OS was defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored on the last date the participant was known to be alive. |
| Percentage of Participants With Immune-Related Best Overall Response (irBOR) | Randomization up to 91 irPFS events (Approximately 19 months) | IrBOR rate was defined as the number of participants whose Immune-related Best Overall Response (irBOR) criteria was Immune-related Complete Response (irCR) or Immune-related Partial Response (irPR), divided by the total number of participants. The immune-related sum of products of diameters (irSPD) incorporates - in addition to the index lesions - measurable new lesions that may have developed on-study, providing an assessment that includes both index and new lesions. irCR=Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR=A 50% or greater decrease, relative to baseline of the irSPD, (based on irSPD of all index lesions and any measurable new lesions). |
Countries
France, Germany, Hong Kong, Italy, Japan, Poland, Russia, Singapore, South Korea, Spain, Taiwan, United States
Participant flow
Recruitment details
Acceptable first-line chemotherapy before randomization to this study for a participant was a regimen containing a fluoropyrimidine agent and a platinum salt. Study initiated July 2012. Primary endpoint July 2014. Study completed April 2015.
Pre-assignment details
114 enrolled and randomized. 29 enrolled but not randomized to treatment group: 26 no longer met study criteria; 2 withdrew consent, 1 other.
Participants by arm
| Arm | Count |
|---|---|
| Ipilimumab Ipilimumab 10 milligram per kilogram body weight (mg/kg) solution intravenously (IV), over 90 minutes, once every 3 weeks for 4 doses, then 10 mg/kg every 12 weeks until disease progression (for a maximum treatment period of 3 years from the first dose). The option of re-introduction, defined as an additional 4 doses of ipilimumab (a dose of 10 mg/kg every 3 weeks) was allowed only at discretion of the investigator if criteria for re-induction were met. | 57 |
| All Best Supportive Care (BSC) BSC may include the continuation of the fluoropyrimidine that was used during the lead-in chemotherapy (prior to randomization to this study), but no other active systemic anti-cancer treatment. | 57 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomized | No longer met criteria | 0 | 2 |
| Randomized | Withdrawal by Subject | 0 | 4 |
| Treated | Adverse Event | 3 | 0 |
| Treated | Death | 1 | 0 |
| Treated | Disease Progression | 39 | 36 |
| Treated | Lost to Follow-up | 0 | 1 |
| Treated | Maximum Clinical Benefit | 0 | 1 |
| Treated | Non-Specified | 1 | 2 |
| Treated | Poor/Non-Compliance | 0 | 1 |
| Treated | Study Drug Toxicity | 9 | 5 |
| Treated | Subject Request | 0 | 1 |
| Treated | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Ipilimumab | All Best Supportive Care (BSC) | Total |
|---|---|---|---|
| Age, Continuous | 65.0 years | 62.0 years | 64.0 years |
| Age, Customized Greater, equal to (>=) 65 years of age | 29 participants | 22 participants | 51 participants |
| Age, Customized Less than (<) 65 years of age | 28 participants | 35 participants | 63 participants |
| Region of Enrollment France | 3 participants | 5 participants | 8 participants |
| Region of Enrollment Germany | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Hong Kong | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Italy | 11 participants | 8 participants | 19 participants |
| Region of Enrollment Japan | 7 participants | 5 participants | 12 participants |
| Region of Enrollment Korea, Republic of | 21 participants | 24 participants | 45 participants |
| Region of Enrollment Poland | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Russian Federation | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Singapore | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Spain | 2 participants | 5 participants | 7 participants |
| Region of Enrollment Taiwan | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 8 participants | 6 participants | 14 participants |
| Sex: Female, Male Female | 21 Participants | 16 Participants | 37 Participants |
| Sex: Female, Male Male | 36 Participants | 41 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 55 / 57 | 42 / 45 | 4 / 6 |
| serious Total, serious adverse events | 31 / 57 | 19 / 45 | 1 / 6 |
Outcome results
Primary
Immune-related Progression Free Survival (irPFS) as Per Assessment of a Blinded Independent Review Committee (IRC) According to Immune Related Response Criteria (irRC) Guidelines
irPFS is defined as the time between the randomization date and the time of disease progression per irRC or death, whichever occurs first. irRC criteria=Measurable new lesions: incorporated into the tumor burden (eg, added to the index lesions); do not define progression unless the total measurable tumor burden increases by the required amount (25%). New non-measurable lesions: not considered progression if the total measurable tumor burden is stable or shrinking. irPFS was measured in months.
Time frame: Randomization up to 91 irPFS events (Approximately 19 months )
Population: All participants who were randomized were summarized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab | Immune-related Progression Free Survival (irPFS) as Per Assessment of a Blinded Independent Review Committee (IRC) According to Immune Related Response Criteria (irRC) Guidelines | 2.9240 Months |
| All Best Supportive Care (BSC) | Immune-related Progression Free Survival (irPFS) as Per Assessment of a Blinded Independent Review Committee (IRC) According to Immune Related Response Criteria (irRC) Guidelines | 4.8950 Months |
p-value: 0.097280% CI: [1.085, 1.908]Log Rank
Secondary
Overall Survival (OS) at Primary Endpoint
OS was defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored on the last date the participant was known to be alive.
Time frame: Randomization up to 91 irPFS events (Approximately 19 months)
Population: All participants randomized to a treatment group and who received at least one dose of active drug were summarized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab | Overall Survival (OS) at Primary Endpoint | 16.7560 Months |
| All Best Supportive Care (BSC) | Overall Survival (OS) at Primary Endpoint | 12.0570 Months |
p-value: 0.643380% CI: [0.602, 1.269]Log Rank
Secondary
Overall Survival (OS) at Study Completion
OS was defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored on the last date the participant was known to be alive.
Time frame: Randomization up to end of study, April 2015 (Approximately 28 months)
Population: All participants randomized to a treatment group and who received at least one dose of active drug were summarized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab | Overall Survival (OS) at Study Completion | 12.68 Months |
| All Best Supportive Care (BSC) | Overall Survival (OS) at Study Completion | 12.06 Months |
Secondary
Percentage of Participants With Immune-Related Best Overall Response (irBOR)
IrBOR rate was defined as the number of participants whose Immune-related Best Overall Response (irBOR) criteria was Immune-related Complete Response (irCR) or Immune-related Partial Response (irPR), divided by the total number of participants. The immune-related sum of products of diameters (irSPD) incorporates - in addition to the index lesions - measurable new lesions that may have developed on-study, providing an assessment that includes both index and new lesions. irCR=Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR=A 50% or greater decrease, relative to baseline of the irSPD, (based on irSPD of all index lesions and any measurable new lesions).
Time frame: Randomization up to 91 irPFS events (Approximately 19 months)
Population: All participants randomized to a treatment group were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ipilimumab | Percentage of Participants With Immune-Related Best Overall Response (irBOR) | 1.8 percentage of participants |
| All Best Supportive Care (BSC) | Percentage of Participants With Immune-Related Best Overall Response (irBOR) | 7.0 percentage of participants |
p-value: 0.368680% CI: [0.7009, 47.6447]Cochran-Mantel-Haenszel
Secondary
Progression Free Survival (PFS) Per Modified World Health Organization (mWHO) Criteria
PFS per mWHO was defined as the time between the randomization date and the time of disease progression per mWHO criteria or death, whichever occurred first and was measured in months. mWHO criteria: New lesions always mean progression; Changes in non-measurable lesions contribute in the definitions of Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD).
Time frame: Randomization up to 91 irPFS events (Approximately 19 months )
Population: All participants randomized to a treatment group were summarized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ipilimumab | Progression Free Survival (PFS) Per Modified World Health Organization (mWHO) Criteria | 2.7270 Months |
| All Best Supportive Care (BSC) | Progression Free Survival (PFS) Per Modified World Health Organization (mWHO) Criteria | 4.8950 Months |
p-value: 0.033680% CI: [1.199, 2.103]Log Rank