Advanced Cancer
Conditions
Brief summary
The primary purpose of this study is to determine whether Nivolumab will improve disease-free survival compared with placebo.
Interventions
DRUGNivolumab
Specified dose on specified days
OTHERPlacebo
Specified dose on specified days
Sponsors
Ono Pharmaceutical Co. Ltd
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with Stage II/III carcinoma of the esophagus or gastroesophageal junction * Completed pre-operative chemo radiotherapy followed by surgery * Diagnosed with residual pathologic disease after being surgically rendered free of disease with negative margins following complete resection
Exclusion criteria
* Diagnosed with cervical esophageal carcinoma * Diagnosed with Stage IV resectable disease * Did not receive concurrent chemoradiotherapy prior to surgery * Participants who have received a live/attenuated vaccine within 30 days of the first treatment Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) | From randomization to the date of recurrence or death (up to approximately 46 months) | Disease-free survival is defined as the time between randomization date and first date of recurrence or death, whichever occurs first. Recurrence is defined as the appearance of one or more new lesions, which can be local, regional, or distant in location from the primary resected site ( assessed by imaging or pathology). All deaths without prior recurrence are considered as DFS events. For participants who remained alive and without recurrence, DFS was censured on the date of last evaluable disease assessment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization to the date of death (up to approximately 60 months) | Overall survival is defined as the time from randomization to the date of death from any cause. For subjects that are alive, their survival time was censored at the date of last contact date (or last known alive date). Overall survival was censored at the date of randomization for subjects who were randomized but had no follow-up. |
| Overall Survival Rates at 12-, 24-, and 36-months | At 12-, 24- and 36-months post first dose. | Overall survival rate is defined as the percentage of participants who are alive at 1, 2 and 3 years following randomization |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Peru, Poland, Puerto Rico, Romania, Russia, Singapore, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
794 participants were randomized and 792 were treated. The reasons for the 2 participants not being treated were: Participant request to discontinue study treatment (1) and Participant no longer meeting study criteria (1).
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab Nivolumab 240 mg Q2W for 8 cycles (16 weeks) followed by Nivolumab 480 mg Q4W for 9 cycles. | 532 |
| Placebo Placebo IV Q2W for 8 cycles (16 weeks) followed by Placebo IV Q4W for 9 cycles | 262 |
| Total | 794 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Pre-treatment Period | Participant no longer meeting study criteria | 0 | 1 |
| Pre-treatment Period | Participant request to discontinue treatment | 0 | 1 |
| Treatment Period | Adverse event unrelated to study drug | 15 | 9 |
| Treatment Period | Death | 1 | 1 |
| Treatment Period | Disease recurrence | 152 | 115 |
| Treatment Period | Lost to Follow-up | 0 | 1 |
| Treatment Period | Other reasons | 4 | 1 |
| Treatment Period | Participant request to discontinue treatment | 31 | 5 |
| Treatment Period | Participant withdrew consent | 11 | 4 |
| Treatment Period | Poor/Non-compliance | 2 | 0 |
| Treatment Period | Study drug toxicity | 56 | 8 |
Baseline characteristics
| Characteristic | Nivolumab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 60.8 Years STANDARD_DEVIATION 9.2 | 59.9 Years STANDARD_DEVIATION 10.1 | 60.5 Years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 33 Participants | 11 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 268 Participants | 144 Participants | 412 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 231 Participants | 107 Participants | 338 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 83 Participants | 34 Participants | 117 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 10 Participants | 7 Participants | 17 Participants |
| Race/Ethnicity, Customized White | 432 Participants | 216 Participants | 648 Participants |
| Sex: Female, Male Female | 83 Participants | 40 Participants | 123 Participants |
| Sex: Female, Male Male | 449 Participants | 222 Participants | 671 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 299 / 532 | 162 / 262 |
| other Total, other adverse events | 470 / 532 | 216 / 260 |
| serious Total, serious adverse events | 196 / 532 | 99 / 260 |
Outcome results
Primary
Disease-free Survival (DFS)
Disease-free survival is defined as the time between randomization date and first date of recurrence or death, whichever occurs first. Recurrence is defined as the appearance of one or more new lesions, which can be local, regional, or distant in location from the primary resected site ( assessed by imaging or pathology). All deaths without prior recurrence are considered as DFS events. For participants who remained alive and without recurrence, DFS was censured on the date of last evaluable disease assessment
Time frame: From randomization to the date of recurrence or death (up to approximately 46 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab | Disease-free Survival (DFS) | 22.41 Months |
| Placebo | Disease-free Survival (DFS) | 11.04 Months |
p-value: 0.000396.4% CI: [0.56, 0.86]Stratified log-rank test
Secondary
Overall Survival (OS)
Overall survival is defined as the time from randomization to the date of death from any cause. For subjects that are alive, their survival time was censored at the date of last contact date (or last known alive date). Overall survival was censored at the date of randomization for subjects who were randomized but had no follow-up.
Time frame: From randomization to the date of death (up to approximately 60 months)
Population: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab | Overall Survival (OS) | 51.71 Months |
| Placebo | Overall Survival (OS) | 35.25 Months |
p-value: 0.106495% CI: [0.07, 1.03]Log Rank
Secondary
Overall Survival Rates at 12-, 24-, and 36-months
Overall survival rate is defined as the percentage of participants who are alive at 1, 2 and 3 years following randomization
Time frame: At 12-, 24- and 36-months post first dose.
Population: All randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nivolumab | Overall Survival Rates at 12-, 24-, and 36-months | 12-months | 87.5 Percent of participants |
| Nivolumab | Overall Survival Rates at 12-, 24-, and 36-months | 24-months | 68.1 Percent of participants |
| Nivolumab | Overall Survival Rates at 12-, 24-, and 36-months | 36-months | 56.9 Percent of participants |
| Placebo | Overall Survival Rates at 12-, 24-, and 36-months | 12-months | 84.6 Percent of participants |
| Placebo | Overall Survival Rates at 12-, 24-, and 36-months | 24-months | 65.8 Percent of participants |
| Placebo | Overall Survival Rates at 12-, 24-, and 36-months | 36-months | 49.7 Percent of participants |