Trial Outcomes & Findings for A Study of Tabalumab (LY2127399) in Participants With Previously Treated Multiple Myeloma (MM) (NCT NCT01602224)

Last Updated: 2019-10-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

220 participants

Primary outcome timeframe

Baseline up to Objective Disease Progression or Death From Any Cause (assessed up to 9 months)

Results posted on

2019-10-08

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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 (BTZ) 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.	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.	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.
Overall Study STARTED	74	74	72
Overall Study Received at Least 1 Dose of Study Drug	73	74	72
Overall Study COMPLETED	66	66	66
Overall Study NOT COMPLETED	8	8	6

Reasons for withdrawal

Reasons for withdrawal
Measure	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 (BTZ) 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.	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.	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.
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

A Study of Tabalumab (LY2127399) in Participants With Previously Treated Multiple Myeloma (MM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	Placebo Comparator: Placebo + Dexamethasone + Bortezomib n=72 Participants 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.	Total n=220 Participants Total of all reporting groups
Age, Continuous	63.2 years STANDARD_DEVIATION 11.01 • n=5 Participants	65.7 years STANDARD_DEVIATION 9.11 • n=7 Participants	65.4 years STANDARD_DEVIATION 9.50 • n=5 Participants	64.8 years STANDARD_DEVIATION 9.93 • n=4 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	37 Participants n=7 Participants	32 Participants n=5 Participants	113 Participants n=4 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	37 Participants n=7 Participants	40 Participants n=5 Participants	107 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=5 Participants	50 Participants n=7 Participants	35 Participants n=5 Participants	124 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	31 Participants n=5 Participants	21 Participants n=7 Participants	32 Participants n=5 Participants	84 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Asian	14 Participants n=5 Participants	18 Participants n=7 Participants	13 Participants n=5 Participants	45 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) White	56 Participants n=5 Participants	53 Participants n=7 Participants	53 Participants n=5 Participants	162 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment United States	11 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	29 Participants n=4 Participants
Region of Enrollment United Kingdom	5 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	16 Participants n=4 Participants
Region of Enrollment Spain	8 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants	21 Participants n=4 Participants
Region of Enrollment Greece	6 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	22 Participants n=4 Participants
Region of Enrollment Canada	2 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment South Korea	6 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	23 Participants n=4 Participants
Region of Enrollment Netherlands	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Turkey	6 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	17 Participants n=4 Participants
Region of Enrollment Taiwan	7 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	18 Participants n=4 Participants
Region of Enrollment Brazil	4 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Region of Enrollment Poland	4 Participants n=5 Participants	13 Participants n=7 Participants	7 Participants n=5 Participants	24 Participants n=4 Participants
Region of Enrollment Italy	7 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment Mexico	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment France	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment Germany	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to Objective Disease Progression or Death From Any Cause (assessed up to 9 months)

Population: All randomized participants.

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	Placebo Comparator: Placebo + Dexamethasone + Bortezomib n=72 Participants 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.
Progression Free Survival (PFS)	6.6 months Interval 5.6 to 8.5	7.5 months Interval 5.8 to 9.3	7.6 months Interval 6.5 to 9.3

SECONDARY outcome

Timeframe: Baseline to Death From Any Cause (assessed up to 19 months)

Population: All randomized participants.

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.

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	Placebo Comparator: Placebo + Dexamethasone + Bortezomib n=72 Participants 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.
Overall Survival	NA months Interval 19.1 to Medians were not reached for timeframe	NA months Medians were not reached for timeframe	NA months Interval 18.6 to Medians were not reached for timeframe

SECONDARY outcome

Timeframe: Baseline to Date of First Skeletal Related Event (assessed up to 19 months)

Population: All randomized participants.

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.

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	Placebo Comparator: Placebo + Dexamethasone + Bortezomib n=72 Participants 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.
Time to First Skeletal-Related Event (SRE)	NA months Medians were not reached for timeframe	NA months Interval 19.8 to Medians were not reached for timeframe	NA months Medians were not reached for timeframe

SECONDARY outcome

Timeframe: Baseline through End of Treatment (19 months)

Population: All randomized participants.

BPI is assessed by 7 questions rated "0" for "no pain" and higher numbers indicated more pain.

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	Placebo Comparator: Placebo + Dexamethasone + Bortezomib n=72 Participants 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.
Number of Participants With >30% Reduction in Brief Pain Inventory (BPI) - Worst Pain Score	37 Participants	30 Participants	30 Participants

SECONDARY outcome

Timeframe: Baseline to Objective Disease Progression or Death (assessed up to 9 months)

Population: All randomized participants, with 79 participants censored.

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.

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	Placebo Comparator: Placebo + Dexamethasone + Bortezomib n=72 Participants 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.
Time to Progression (TTP)	6.6 months Interval 5.9 to 9.3	8.2 months Interval 6.4 to 11.2	8.1 months Interval 6.9 to 9.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=43 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=44 Participants 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.	Placebo Comparator: Placebo + Dexamethasone + Bortezomib n=44 Participants 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.
Duration of Response (DoR)	7.9 months Interval 6.0 to 11.6	8.6 months Interval 6.5 to 10.7	7.7 months Interval 5.8 to 13.1

SECONDARY outcome

Timeframe: Baseline to Initiation of New Cancer Treatment or Death From Any Cause (18 Months)

Population: All randomized participants.

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.

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	Placebo Comparator: Placebo + Dexamethasone + Bortezomib n=72 Participants 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.
Time to Next Treatment (TNT)	10.1 months Interval 7.0 to 11.9	9.9 months Interval 6.8 to 14.8	11.7 months Interval 7.8 to 17.5

SECONDARY outcome

Timeframe: 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.

Maximum Concentration (Cmax) of Tabalumab.

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=68 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=71 Participants 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.	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.
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab Cycle 1	38.0 micrograms per milliliter Geometric Coefficient of Variation 39	103 micrograms per milliliter Geometric Coefficient of Variation 43	—
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab Cycle 2	47.9 micrograms per milliliter Geometric Coefficient of Variation 51	131 micrograms per milliliter Geometric Coefficient of Variation 40	—
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Tabalumab Steady State (Cycle 6-10)	69.0 micrograms per milliliter Geometric Coefficient of Variation 51	189 micrograms per milliliter Geometric Coefficient of Variation 54	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=73 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	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.
PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab Cycle 1	1.5 hours Interval 0.75 to 503.75	1.58 hours Interval 0.92 to 162.58	—
PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab Cycle 2	0.92 hours Interval 0.47 to 503.77	0.76 hours Interval 0.5 to 503.58	—
PK: Time to Maximum Plasma Concentration (Tmax) of Tabalumab Steady State (Cycle 6-10)	0.75 hours Interval 0.338 to 9.92	0.73 hours Interval 0.0 to 1.75	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=68 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=71 Participants 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.	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.
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	2220 micrograms times hour per milliliter Geometric Coefficient of Variation 44	—
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	35400 micrograms times hour per milliliter Geometric Coefficient of Variation 49	—
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	70100 micrograms times hour per milliliter Geometric Coefficient of Variation 52	—

SECONDARY outcome

Timeframe: Baseline through Cycle 8

Population: Zero participants analyzed, no data collected due to compound termination.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (28 Months)

Population: All randomized participants.

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

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	Placebo Comparator: Placebo + Dexamethasone + Bortezomib n=72 Participants 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.
Participants With Best Overall Response (BOR) in Each Category Stringent Complete Response	1 Participants	0 Participants	2 Participants
Participants With Best Overall Response (BOR) in Each Category Complete Response	10 Participants	4 Participants	4 Participants
Participants With Best Overall Response (BOR) in Each Category Very Good Partial Response	10 Participants	16 Participants	9 Participants
Participants With Best Overall Response (BOR) in Each Category Partial Response	23 Participants	23 Participants	29 Participants
Participants With Best Overall Response (BOR) in Each Category Minimal Response	6 Participants	8 Participants	6 Participants
Participants With Best Overall Response (BOR) in Each Category Stable Disease	14 Participants	10 Participants	12 Participants
Participants With Best Overall Response (BOR) in Each Category Progressive Disease	6 Participants	7 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (up to 28 Months)

Population: All randomized participants.

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.

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	Placebo Comparator: Placebo + Dexamethasone + Bortezomib n=72 Participants 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.
Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) Very Good Partial Response	10 participants	16 participants	9 participants
Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) Partial Response	23 participants	23 participants	29 participants
Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) Minimal Response	6 participants	8 participants	6 participants
Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) Stable Disease	14 participants	10 participants	12 participants
Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) Progressive Disease	6 participants	7 participants	6 participants
Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) Stringent Complete Response	1 participants	0 participants	2 participants
Number of Participants With a Given Best Objective Myeloma Response (Quality of Response [QoR]) Complete Response	10 participants	4 participants	4 participants

SECONDARY outcome

Timeframe: Baseline to Objective Disease Progression or Initiation of New Cancer Treatment (28 Months)

Population: All randomized participants who had a partial response or greater.

Overall Response Rate (ORR) is the percentage of participants that had a response.

Outcome measures

Outcome measures
Measure	100 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	300 mg Tabalumab+Dexamethasone+Bortezomib n=74 Participants 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.	Placebo Comparator: Placebo + Dexamethasone + Bortezomib n=72 Participants 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.
Overall Response Rate (ORR)	58.1 percentage of participants	59.5 percentage of participants	61.1 percentage of participants

Adverse Events

100 mg Tabalumab+Dexamethasone+Bortezomib

Serious events: 33 serious events

Other events: 71 other events

Deaths: 0 deaths

300 mg Tabalumab+Dexamethasone+Bortezomib

Serious events: 35 serious events

Other events: 70 other events

Deaths: 0 deaths

Placebo Comparator: Placebo + Dexamethasone + Bortezomib

Serious events: 26 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60