Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to evaluate an investigational drug called tabalumab in participants with Multiple Myeloma (MM) who have tried at least one other therapy in the past. Tabalumab will be given in combination with standard doses of two other drugs that are often used to treat MM. Study doctors will collect information about the effectiveness and side effects of this therapy.
Interventions
DRUGPlacebo
Administered IV
DRUGDexamethasone
Administered orally
DRUGBortezomib
Administered SQ
BIOLOGICALTabalumab
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have symptomatic and/or progressive MM that was previously treated with at least 1 and no more than 3 prior lines of therapy * Have measurable disease * Have given written informed consent prior to any study-specific procedures * Have adequate organ function * Treatment with prior autologous transplant is permitted
Exclusion criteria
* Are enrolled in or discontinued from a clinical trial of any drug or device within 21 days prior to the first dose of assigned study treatment * Have had less than a minimal response or have had progressive disease within 60 days of most recent therapy with a proteasome inhibitor * Plan to proceed to autologous transplant for consolidation after participation in this trial * Have an active infection or ongoing treatment for systemic infection (ongoing treatment does not include prophylactic anti-infectives),, chest x-ray suggestive of tuberculosis, or history/risk of chronic/latent infection that may reactivate in the presence of study therapy * Have any of the following: * positive test results for human immunodeficiency virus (HIV) * positive test for hepatitis B, defined as positive for hepatitis B surface antigen (HBsAg+), OR positive for anti-hepatitis B core antibody AND positive for hepatitis B deoxyribonucleic acid (HBV DNA), OR positive for anti-hepatitis B surface antibody (HBsAb+) AND positive for hepatitis B deoxyribonucleic acid (HBV DNA) * positive test results for hepatitis C virus (HCV), defined as positive for hepatitis C antibody (HepCAb) AND confirmed positive via the hepatitis C recombinant immunoblot assay * Have had significant allergy to human/humanized monoclonal antibodies that, in the opinion of the investigator, poses an unacceptable risk to the participants * Have known hypersensitivity or contraindication to any of the study therapies or excipients * Prior allogeneic hematopoietic stem cell transplant * Prior therapy with experimental agents targeting B-cell activating factor (BAFF), including LY2127399 * Have corrected QT (QTc) interval \>500 millisecond (msec) on baseline 12-lead electrocardiogram (ECG) * Have Waldenstrom's macroglobulinemia * History of malignancy with adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer, are eligible regardless of the time of diagnosis/treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Baseline up to Objective Disease Progression or Death From Any Cause (assessed up to 9 months) | PFS is defined as the time from date of first dose to the first observation of disease progression or death due to any cause. If a participant does not have a complete baseline disease assessment, then the PFS time is censored at the enrollment date, regardless of whether or not objectively determined disease progression (Increase of \> 25% from lowest response in serum M component, urine M component, bone marrow plasma cell percentage, development of bone lesions) or death has been observed for the participant. If a participant is not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time is censored at the last complete objective progression-free disease assessment date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab | Cycle (C)1 Day (D)1: Predose, 3O minutes, 2 hours Postdose; C1 D4, 8, 11: Predose, (D11 only, 30 minutes Postdose); C2 and C6-C10 D1: Predose and immediately Postdose; C2 D 4, 8, 11: Anytime | Maximum Concentration (Cmax) of Tabalumab. |
| Time to First Skeletal-Related Event (SRE) | Baseline to Date of First Skeletal Related Event (assessed up to 19 months) | Time to first SRE is defined as time from randomization to any one of the following related to multiple myeloma: New Pathological Fracture, Spinal Cord Compression, Surgery to the Bone, Radiation to the Bone collected until participant death, study closure or lost to follow up. Participants not known to have had an SRE at the time of the analysis were censored at the date of their last complete documented assessment for SRE. |
| Number of Participants With >30% Reduction in Brief Pain Inventory (BPI) - Worst Pain Score | Baseline through End of Treatment (19 months) | BPI is assessed by 7 questions rated 0 for no pain and higher numbers indicated more pain. |
| Time to Progression (TTP) | Baseline to Objective Disease Progression or Death (assessed up to 9 months) | Time to progression is defined as the time from the date of randomization to the date of first observed objective progression or death due to study disease. Time to progression will be censored as for PFS for those participants not known to have progressed or that died from other causes. |
| Duration of Response (DoR) | Time from Response to Objective Disease Progression (assessed up to 38 months) | DOR is measured by the International Myeloma Working Group Uniform Response Criteria: from the date of first evidence of a confirmed response to the date of objective progression or the date of death due to any cause, whichever is earlier. If a responder is not known to have died or have objective progression as of the data inclusion cutoff date, the DOR time will be censored at the last complete objective progression-free disease assessment date. Progressive disease is an increase of 25% from baseline in Serum M, Urine M, bone marrow plasma cell increase of 10 %, development of new bone lesions, development of new soft tissue plasmacytomas or bone lesions, hypercalcemia \>11.5 milligrams per deciliter, decrease in hemoglobin of 2 grams per deciliter, rise in serum creatinine by 2 mg/deciliter. |
| Time to Next Treatment (TNT) | Baseline to Initiation of New Cancer Treatment or Death From Any Cause (18 Months) | TNT is defined as the time from the date of randomization to the date of initiation of the first poststudy treatment course of anticancer therapy or death from any cause. Time to next treatment will be censored at the date of the last visit for participant who did not initiate additional anticancer therapy. |
| Overall Survival | Baseline to Death From Any Cause (assessed up to 19 months) | Overall survival is the duration from enrollment to death from any cause. For participants who were alive, overall survival was censored at the last contact. |
| PK: Area Under the Curve Over the Dosing Interval (AUC-T) for Tabalumab | C1 D1: Predose, 3O minutes, 2 hours Postdose; C1 D4, 8, 11: Predose, (D11 only, 30 minutes Postdose); C2 and C6-C10 D1: Predose and immediately Postdose; C2 D 4, 8, 11: Anytime | — |
| Number of Participants Developing Anti-tabalumab Antibodies | Baseline through Cycle 8 | — |
| Participants With Best Overall Response (BOR) in Each Category | Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (28 Months) | Stringent Complete Response-Complete Response and normal free light chain ration and no clonal cells in bone marrow Complete Response- no monoclonal protein (mp) in blood, no serum or urine mp, less than 5% plasma cells in bone marrow Very Good Partial Response-more than 90% decrease in mp and urine protein Partial Response- over 50% decrease in serum mp Stable Disease- less than 25 percent decrease of monoclonal protein Progressive Disease- 25% increase compared to lowest value of serum mp, urine mp, no measurable mp |
| Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (up to 28 Months) | Response categories in order of decreasing quality are: Stringent Complete Response(sCR),Complete Response(CR), Very Good Partial Response(VGPR),Partial Response(PR),Minimal Response(MR),Stable Disease(SD), or Progressive Disease(PD), according to the International Uniform Response Criteria for Multiple Myeloma.SCR:normal free light chain ration and no clonal cells in bone marrow;CR-no monoclonal protein(mp) in blood, no serum/urine,\<5% plasma cells in bone marrow; VGPR-more than 90% decrease in mp and urine protein; PR-\>50% decrease in serum MP;SD-\<25% decrease in mp; PD-25% increase compared to lowest value of serum mp, urine mp and no measurable mp. |
| Overall Response Rate (ORR) | Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (28 Months) | Overall Response Rate (ORR) is the percentage of participants that had a response. |
| PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab | C1 D1: Predose, 3O minutes, 2 hours Postdose; C1 D4, 8, 11: Predose, (D11 only, 30 minutes Postdose); C2 and C6-C10 D1: Predose and immediately Postdose; C2 D 4, 8, 11: Anytime | — |
Countries
Brazil, Canada, France, Germany, Greece, Italy, Mexico, Netherlands, Poland, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
Completers are defined as participants who died or had disease progression or completed treatment or did not complete treatment and were followed for survival data.
Participants by arm
| Arm | Count |
|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib Tabalumab 100 milligram (mg) administered once intravenously (IV) over 30 minutes on Day 1 every 21 days for 8 cycles.
Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles.
Bortezomib 1.3 milligram per square meter (mg/m\^2) administered once subcutaneously (SQ) on Days 1, 4, 8 and 11 every 21 days for 8 cycles. | 74 |
| 300 mg Tabalumab+Dexamethasone+Bortezomib Tabalumab 300 mg administered once IV over 30 minutes on Day 1 every 21 days for 8 cycles.
Dexamethasone 20 mg administered orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles.
Bortezomib 1.3 mg/m\^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles. | 74 |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib Placebo administered once IV on Day 1 every 21 days for 8 cycles.
Dexamethasone 20 mg administered once orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 every 21 days for 8 cycles.
Bortezomib 1.3 mg/m\^2 administered once SQ on Days 1, 4, 8 and 11 every 21 days for 8 cycles. | 72 |
| Total | 220 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Investigator Decison | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Sponsor Decision | 2 | 3 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 3 | 3 |
Baseline characteristics
| Characteristic | 300 mg Tabalumab+Dexamethasone+Bortezomib | Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Total | 100 mg Tabalumab+Dexamethasone+Bortezomib |
|---|---|---|---|---|
| Age, Continuous | 65.7 years STANDARD_DEVIATION 9.11 | 65.4 years STANDARD_DEVIATION 9.5 | 64.8 years STANDARD_DEVIATION 9.93 | 63.2 years STANDARD_DEVIATION 11.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 12 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 35 Participants | 124 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 21 Participants | 32 Participants | 84 Participants | 31 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 13 Participants | 45 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 53 Participants | 53 Participants | 162 Participants | 56 Participants |
| Region of Enrollment Brazil | 2 Participants | 5 Participants | 11 Participants | 4 Participants |
| Region of Enrollment Canada | 2 Participants | 0 Participants | 4 Participants | 2 Participants |
| Region of Enrollment France | 3 Participants | 6 Participants | 12 Participants | 3 Participants |
| Region of Enrollment Germany | 1 Participants | 1 Participants | 4 Participants | 2 Participants |
| Region of Enrollment Greece | 7 Participants | 9 Participants | 22 Participants | 6 Participants |
| Region of Enrollment Italy | 2 Participants | 3 Participants | 12 Participants | 7 Participants |
| Region of Enrollment Mexico | 1 Participants | 2 Participants | 6 Participants | 3 Participants |
| Region of Enrollment Netherlands | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Poland | 13 Participants | 7 Participants | 24 Participants | 4 Participants |
| Region of Enrollment South Korea | 9 Participants | 8 Participants | 23 Participants | 6 Participants |
| Region of Enrollment Spain | 5 Participants | 8 Participants | 21 Participants | 8 Participants |
| Region of Enrollment Taiwan | 6 Participants | 5 Participants | 18 Participants | 7 Participants |
| Region of Enrollment Turkey | 7 Participants | 4 Participants | 17 Participants | 6 Participants |
| Region of Enrollment United Kingdom | 7 Participants | 4 Participants | 16 Participants | 5 Participants |
| Region of Enrollment United States | 9 Participants | 9 Participants | 29 Participants | 11 Participants |
| Sex: Female, Male Female | 37 Participants | 32 Participants | 113 Participants | 44 Participants |
| Sex: Female, Male Male | 37 Participants | 40 Participants | 107 Participants | 30 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 | 71 / 73 | 70 / 74 | 69 / 72 |
| serious Total, serious adverse events | 33 / 73 | 35 / 74 | 26 / 72 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS is defined as the time from date of first dose to the first observation of disease progression or death due to any cause. If a participant does not have a complete baseline disease assessment, then the PFS time is censored at the enrollment date, regardless of whether or not objectively determined disease progression (Increase of \> 25% from lowest response in serum M component, urine M component, bone marrow plasma cell percentage, development of bone lesions) or death has been observed for the participant. If a participant is not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time is censored at the last complete objective progression-free disease assessment date.
Time frame: Baseline up to Objective Disease Progression or Death From Any Cause (assessed up to 9 months)
Population: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Progression Free Survival (PFS) | 6.6 months |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Progression Free Survival (PFS) | 7.5 months |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Progression Free Survival (PFS) | 7.6 months |
Secondary
Duration of Response (DoR)
DOR is measured by the International Myeloma Working Group Uniform Response Criteria: from the date of first evidence of a confirmed response to the date of objective progression or the date of death due to any cause, whichever is earlier. If a responder is not known to have died or have objective progression as of the data inclusion cutoff date, the DOR time will be censored at the last complete objective progression-free disease assessment date. Progressive disease is an increase of 25% from baseline in Serum M, Urine M, bone marrow plasma cell increase of 10 %, development of new bone lesions, development of new soft tissue plasmacytomas or bone lesions, hypercalcemia \>11.5 milligrams per deciliter, decrease in hemoglobin of 2 grams per deciliter, rise in serum creatinine by 2 mg/deciliter.
Time frame: Time from Response to Objective Disease Progression (assessed up to 38 months)
Population: All randomized participants who received at least 1 dose of study drug and had a response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Duration of Response (DoR) | 7.9 months |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Duration of Response (DoR) | 8.6 months |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Duration of Response (DoR) | 7.7 months |
Secondary
Number of Participants Developing Anti-tabalumab Antibodies
Time frame: Baseline through Cycle 8
Population: Zero participants analyzed, no data collected due to compound termination.
Secondary
Number of Participants With >30% Reduction in Brief Pain Inventory (BPI) - Worst Pain Score
BPI is assessed by 7 questions rated 0 for no pain and higher numbers indicated more pain.
Time frame: Baseline through End of Treatment (19 months)
Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With >30% Reduction in Brief Pain Inventory (BPI) - Worst Pain Score | 37 Participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With >30% Reduction in Brief Pain Inventory (BPI) - Worst Pain Score | 30 Participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Number of Participants With >30% Reduction in Brief Pain Inventory (BPI) - Worst Pain Score | 30 Participants |
Secondary
Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR])
Response categories in order of decreasing quality are: Stringent Complete Response(sCR),Complete Response(CR), Very Good Partial Response(VGPR),Partial Response(PR),Minimal Response(MR),Stable Disease(SD), or Progressive Disease(PD), according to the International Uniform Response Criteria for Multiple Myeloma.SCR:normal free light chain ration and no clonal cells in bone marrow;CR-no monoclonal protein(mp) in blood, no serum/urine,\<5% plasma cells in bone marrow; VGPR-more than 90% decrease in mp and urine protein; PR-\>50% decrease in serum MP;SD-\<25% decrease in mp; PD-25% increase compared to lowest value of serum mp, urine mp and no measurable mp.
Time frame: Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (up to 28 Months)
Population: All randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Very Good Partial Response | 10 participants |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Stable Disease | 14 participants |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Minimal Response | 6 participants |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Progressive Disease | 6 participants |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Partial Response | 23 participants |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Stringent Complete Response | 1 participants |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Complete Response | 10 participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Minimal Response | 8 participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Very Good Partial Response | 16 participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Progressive Disease | 7 participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Partial Response | 23 participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Stable Disease | 10 participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Stringent Complete Response | 0 participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Complete Response | 4 participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Minimal Response | 6 participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Stable Disease | 12 participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Progressive Disease | 6 participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Complete Response | 4 participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Very Good Partial Response | 9 participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Partial Response | 29 participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) | Stringent Complete Response | 2 participants |
Comparison: 100 mg Tabalumab+Dexamethasone+Bortezomib compared with Placebo Comparator: Placebo + Dexamethasone + Bortezombib, only tabalumab odds ratio compared to placebo.p-value: 0.401Regression, Logistic
Comparison: 300 mg Tabalumab+Dexamethasone+Bortezomib compared with Placebo Comparator: Placebo + Dexamethasone + Bortezombib, only tabalumab odds ratio compared to placebo.p-value: 0.455Regression, Logistic
Comparison: 100 mg Tabalumab+Dexamethasone+Bortezomib and 300 mg Tabalumab+Dexamethasone+Bortezomib compared with Placebo Comparator: Placebo + Dexamethasone + Bortezombib, only compared to placebo.p-value: 0.419Regression, Logistic
Secondary
Overall Response Rate (ORR)
Overall Response Rate (ORR) is the percentage of participants that had a response.
Time frame: Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (28 Months)
Population: All randomized participants who had a partial response or greater.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Overall Response Rate (ORR) | 58.1 percentage of participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Overall Response Rate (ORR) | 59.5 percentage of participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Overall Response Rate (ORR) | 61.1 percentage of participants |
Secondary
Overall Survival
Overall survival is the duration from enrollment to death from any cause. For participants who were alive, overall survival was censored at the last contact.
Time frame: Baseline to Death From Any Cause (assessed up to 19 months)
Population: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Overall Survival | NA months |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Overall Survival | NA months |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Overall Survival | NA months |
Secondary
Participants With Best Overall Response (BOR) in Each Category
Stringent Complete Response-Complete Response and normal free light chain ration and no clonal cells in bone marrow Complete Response- no monoclonal protein (mp) in blood, no serum or urine mp, less than 5% plasma cells in bone marrow Very Good Partial Response-more than 90% decrease in mp and urine protein Partial Response- over 50% decrease in serum mp Stable Disease- less than 25 percent decrease of monoclonal protein Progressive Disease- 25% increase compared to lowest value of serum mp, urine mp, no measurable mp
Time frame: Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (28 Months)
Population: All randomized participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Stable Disease | 14 Participants |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Minimal Response | 6 Participants |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Very Good Partial Response | 10 Participants |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Complete Response | 10 Participants |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Progressive Disease | 6 Participants |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Stringent Complete Response | 1 Participants |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Partial Response | 23 Participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Very Good Partial Response | 16 Participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Complete Response | 4 Participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Partial Response | 23 Participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Stringent Complete Response | 0 Participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Minimal Response | 8 Participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Stable Disease | 10 Participants |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Progressive Disease | 7 Participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Partial Response | 29 Participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Minimal Response | 6 Participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Stringent Complete Response | 2 Participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Progressive Disease | 6 Participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Stable Disease | 12 Participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Very Good Partial Response | 9 Participants |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Participants With Best Overall Response (BOR) in Each Category | Complete Response | 4 Participants |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab
Maximum Concentration (Cmax) of Tabalumab.
Time frame: Cycle (C)1 Day (D)1: Predose, 3O minutes, 2 hours Postdose; C1 D4, 8, 11: Predose, (D11 only, 30 minutes Postdose); C2 and C6-C10 D1: Predose and immediately Postdose; C2 D 4, 8, 11: Anytime
Population: All randomized participants who received at least 1 dose of study drug and evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab | Cycle 1 | 38.0 micrograms per milliliter | Geometric Coefficient of Variation 39 |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab | Steady State (Cycle 6-10) | 69.0 micrograms per milliliter | Geometric Coefficient of Variation 51 |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab | Cycle 2 | 47.9 micrograms per milliliter | Geometric Coefficient of Variation 51 |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab | Cycle 1 | 103 micrograms per milliliter | Geometric Coefficient of Variation 43 |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab | Steady State (Cycle 6-10) | 189 micrograms per milliliter | Geometric Coefficient of Variation 54 |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab | Cycle 2 | 131 micrograms per milliliter | Geometric Coefficient of Variation 40 |
Secondary
PK: Area Under the Curve Over the Dosing Interval (AUC-T) for Tabalumab
Time frame: C1 D1: Predose, 3O minutes, 2 hours Postdose; C1 D4, 8, 11: Predose, (D11 only, 30 minutes Postdose); C2 and C6-C10 D1: Predose and immediately Postdose; C2 D 4, 8, 11: Anytime
Population: All randomized participants who received at least 1 dose of study drug and had evaluable PK parameters.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | PK: Area Under the Curve Over the Dosing Interval (AUC-T) for Tabalumab | Cycle 1 | 7790 micrograms times hour per milliliter | Geometric Coefficient of Variation 42 |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | PK: Area Under the Curve Over the Dosing Interval (AUC-T) for Tabalumab | Cycle 2 | 11600 micrograms times hour per milliliter | Geometric Coefficient of Variation 36 |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | PK: Area Under the Curve Over the Dosing Interval (AUC-T) for Tabalumab | Steady State (Cycle 6-10) | 25300 micrograms times hour per milliliter | Geometric Coefficient of Variation 57 |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | PK: Area Under the Curve Over the Dosing Interval (AUC-T) for Tabalumab | Cycle 2 | 35400 micrograms times hour per milliliter | Geometric Coefficient of Variation 49 |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | PK: Area Under the Curve Over the Dosing Interval (AUC-T) for Tabalumab | Cycle 1 | 2220 micrograms times hour per milliliter | Geometric Coefficient of Variation 44 |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | PK: Area Under the Curve Over the Dosing Interval (AUC-T) for Tabalumab | Steady State (Cycle 6-10) | 70100 micrograms times hour per milliliter | Geometric Coefficient of Variation 52 |
Secondary
PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab
Time frame: C1 D1: Predose, 3O minutes, 2 hours Postdose; C1 D4, 8, 11: Predose, (D11 only, 30 minutes Postdose); C2 and C6-C10 D1: Predose and immediately Postdose; C2 D 4, 8, 11: Anytime
Population: All randomized participants who received at least 1 dose of study drug with evaluable PK values.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab | Cycle 1 | 1.5 hours |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab | Cycle 2 | 0.92 hours |
| 100 mg Tabalumab+Dexamethasone+Bortezomib | PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab | Steady State (Cycle 6-10) | 0.75 hours |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab | Cycle 1 | 1.58 hours |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab | Cycle 2 | 0.76 hours |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab | Steady State (Cycle 6-10) | 0.73 hours |
Secondary
Time to First Skeletal-Related Event (SRE)
Time to first SRE is defined as time from randomization to any one of the following related to multiple myeloma: New Pathological Fracture, Spinal Cord Compression, Surgery to the Bone, Radiation to the Bone collected until participant death, study closure or lost to follow up. Participants not known to have had an SRE at the time of the analysis were censored at the date of their last complete documented assessment for SRE.
Time frame: Baseline to Date of First Skeletal Related Event (assessed up to 19 months)
Population: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Time to First Skeletal-Related Event (SRE) | NA months |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Time to First Skeletal-Related Event (SRE) | NA months |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Time to First Skeletal-Related Event (SRE) | NA months |
Secondary
Time to Next Treatment (TNT)
TNT is defined as the time from the date of randomization to the date of initiation of the first poststudy treatment course of anticancer therapy or death from any cause. Time to next treatment will be censored at the date of the last visit for participant who did not initiate additional anticancer therapy.
Time frame: Baseline to Initiation of New Cancer Treatment or Death From Any Cause (18 Months)
Population: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Time to Next Treatment (TNT) | 10.1 months |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Time to Next Treatment (TNT) | 9.9 months |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Time to Next Treatment (TNT) | 11.7 months |
Secondary
Time to Progression (TTP)
Time to progression is defined as the time from the date of randomization to the date of first observed objective progression or death due to study disease. Time to progression will be censored as for PFS for those participants not known to have progressed or that died from other causes.
Time frame: Baseline to Objective Disease Progression or Death (assessed up to 9 months)
Population: All randomized participants, with 79 participants censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg Tabalumab+Dexamethasone+Bortezomib | Time to Progression (TTP) | 6.6 months |
| 300 mg Tabalumab+Dexamethasone+Bortezomib | Time to Progression (TTP) | 8.2 months |
| Placebo Comparator: Placebo + Dexamethasone + Bortezomib | Time to Progression (TTP) | 8.1 months |