Multiple Myeloma
Conditions
Brief summary
Study of elotuzumab in combination with pomalidomide and low dose dexamethasone (EPd Cohort) and elotuzumab in combination with nivolumab (EN Cohort) to assess the safety and efficacy of these combination therapies for treatment of relapsed or refractory MM patients.
Interventions
DRUGElotuzumab
DRUGPomalidomide
DRUGDexamethasone
DRUGNivolumab
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 Inclusion Criteria: 1. All subjects must have documented disease progression per IMWG criteria during or after their last anti-myeloma therapy. 2. ECOG Performance Status less than or equal to 2 3. Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (ie, has not been treated). If re-enrolled, the subject must be re-consented. 4. EPd Cohort: * must have received at least 1 but no greater than 2 prior lines of therapy (note: induction and stem cell transplants with or without maintenance therapy is considered 1 line of therapy) * Subjects must have received prior treatment with a lenalidomide-containing regimen for at least 2 consecutive cycles (full therapeutic dose) and must have been deemed as relapsed, refractory, or intolerant. Refractory is defined as progressing on-treatment or within 60 days of the last dose. 5. EN Cohort: * Subjects must have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory (IMID) agent OR were double-refractory to both an IMID and a PI. Refractory is defined as progressing on-treatment or within 60 days of the last dose.
Exclusion criteria
1. Subjects with solitary bone or extramedullary plasmacytoma as the only evidence of plasma cells dyscrasia 2. Subjects with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), primary amyloidosis, Waldenstrom's macroglobulinemia, or POEMS syndrome (plasma cell dyscrasia with poly neuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 3. Subjects with Central Nervous System involvement with multiple myeloma Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From first dose to study completion date (up to approximately 50 months) | PFS is defined as the time from first dosing date to the date of the first documented progression or death due to any cause, whichever occurs first. Progression is determined per International Myeloma Working Group (IMWG) uniform criteria. Participants who die without a reported prior progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable assessment. Participants who did not have any on study efficacy assessments and did not die were censored on the first dosing date. Participants who switched to subsequent therapy prior to documented progression were censored on the date of the last evaluable assessment prior to the initiation of the new therapy. |
| Objective Response Rate (ORR) | From first dose to study completion date (up to approximately 50 months) | ORR is defined as the percent of participants with best overall response of partial response (PR) or better. Response is determined per IMWG uniform criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From first dose to study completion date (up to approximately 50 months) | ORR is defined as the percent of participants with best overall response of partial response (PR) or better. Response is determined per IMWG uniform criteria. |
| Progression Free Survival (PFS) | From first dose to study completion date (up to approximately 50 months) | PFS is defined as the time from first dosing date to the date of the first documented progression or death due to any cause, whichever occurs first. Progression is determined per International Myeloma Working Group (IMWG) uniform criteria. Participants who die without a reported prior progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable assessment. Participants who did not have any on study efficacy assessments and did not die were censored on the first dosing date. Participants who switched to subsequent therapy prior to documented progression were censored on the date of the last evaluable assessment prior to the initiation of the new therapy. |
| Overall Survival (OS) | From first dose to study completion date (up to approximately 50 months) | OS is defined as the time from first dosing date to the date of death from any cause. |
Countries
United States
Participant flow
Pre-assignment details
EPd cohort: 68 participants entered the treatment period. EN cohort: 6 participants entered the treatment period.
Participants by arm
| Arm | Count |
|---|---|
| EPd Cohort Participants received treatment with Elotuzumab in combination with Pomalidomide and low-dose Dexamethasone in a 28 day cycle. | 68 |
| EN Cohort Participants received Elotuzumab in combination with Nivolumab in a 28-day cycle. | 6 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 4 | 1 |
| Overall Study | Adverse event unrelated to study drug | 5 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Disease progression | 29 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Maximum clinical benefit | 10 | 1 |
| Overall Study | No longer meet study criteria | 0 | 1 |
| Overall Study | Other reasons | 4 | 0 |
| Overall Study | Participant withdrew consent | 4 | 0 |
| Overall Study | Study drug toxicity | 10 | 1 |
Baseline characteristics
| Characteristic | EPd Cohort | EN Cohort | Total |
|---|---|---|---|
| Age, Continuous | 65.3 Years STANDARD_DEVIATION 9.11 | 69.5 Years STANDARD_DEVIATION 10.56 | 65.6 Years STANDARD_DEVIATION 9.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 6 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian1 | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 58 Participants | 3 Participants | 61 Participants |
| Sex: Female, Male Female | 33 Participants | 3 Participants | 36 Participants |
| Sex: Female, Male Male | 35 Participants | 3 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 32 / 68 | 2 / 6 |
| other Total, other adverse events | 66 / 68 | 4 / 6 |
| serious Total, serious adverse events | 39 / 68 | 3 / 6 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR is defined as the percent of participants with best overall response of partial response (PR) or better. Response is determined per IMWG uniform criteria.
Time frame: From first dose to study completion date (up to approximately 50 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EPd Cohort | Objective Response Rate (ORR) | 16.7 Percent of Participants |
Primary
Progression Free Survival (PFS)
PFS is defined as the time from first dosing date to the date of the first documented progression or death due to any cause, whichever occurs first. Progression is determined per International Myeloma Working Group (IMWG) uniform criteria. Participants who die without a reported prior progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable assessment. Participants who did not have any on study efficacy assessments and did not die were censored on the first dosing date. Participants who switched to subsequent therapy prior to documented progression were censored on the date of the last evaluable assessment prior to the initiation of the new therapy.
Time frame: From first dose to study completion date (up to approximately 50 months)
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EPd Cohort | Progression Free Survival (PFS) | 11.1 Months |
Secondary
Objective Response Rate (ORR)
ORR is defined as the percent of participants with best overall response of partial response (PR) or better. Response is determined per IMWG uniform criteria.
Time frame: From first dose to study completion date (up to approximately 50 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EPd Cohort | Objective Response Rate (ORR) | 51.5 Percent of Participants |
Secondary
Overall Survival (OS)
OS is defined as the time from first dosing date to the date of death from any cause.
Time frame: From first dose to study completion date (up to approximately 50 months)
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EPd Cohort | Overall Survival (OS) | 41.2 Months |
| EN Cohort | Overall Survival (OS) | NA Months |
Secondary
Progression Free Survival (PFS)
PFS is defined as the time from first dosing date to the date of the first documented progression or death due to any cause, whichever occurs first. Progression is determined per International Myeloma Working Group (IMWG) uniform criteria. Participants who die without a reported prior progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable assessment. Participants who did not have any on study efficacy assessments and did not die were censored on the first dosing date. Participants who switched to subsequent therapy prior to documented progression were censored on the date of the last evaluable assessment prior to the initiation of the new therapy.
Time frame: From first dose to study completion date (up to approximately 50 months)
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EPd Cohort | Progression Free Survival (PFS) | 1.9 Months |