Trial Outcomes & Findings for A Study of Oral Ixazomib Maintenance Therapy in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Not Treated With Stem Cell Transplantation (SCT) (NCT NCT02312258)

Last Updated: 2023-09-21

Results Overview

PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause, as evaluated by an independent review committee (IRC) according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first. Per IMWG criteria, PD is defined as, increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase ≥0.5 g/ deciliter (dL)); or urine M-component (absolute increase ≥200 mg/24-hour); difference between involved and uninvolved free light chains (FLC) levels (absolute increase \>10 mg/dL); or bone marrow plasma cell percentage (absolute plasma cell percentage ≥10%); development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma; or development of hypercalcemia (corrected serum calcium \>11.5mg/dL).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

706 participants

Primary outcome timeframe

From randomization until PD or death (up to 52 months)

Results posted on

2023-09-21

Participant Flow

Participants took part in the study from 09 April 2015 to 26 August 2022.

Participants with newly diagnosed multiple myeloma not treated with stem cell transplantation (SCT) were enrolled and randomized in a 3:2 ratio to receive ixazomib or placebo respectively.

Participant milestones

Participant milestones
Measure	Placebo Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Overall Study STARTED	281	425
Overall Study Safety Population	276	426
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	281	425

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Overall Study Lost to Follow-up	8	8
Overall Study Withdrawal by Patient	49	76
Overall Study Reason not Specified	107	159
Overall Study Missing	2	1
Overall Study Death	115	181

Baseline Characteristics

A Study of Oral Ixazomib Maintenance Therapy in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Not Treated With Stem Cell Transplantation (SCT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=281 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=425 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.	Total n=706 Participants Total of all reporting groups
Region of Enrollment Poland	2 Participants n=5 Participants	13 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment Portugal	6 Participants n=5 Participants	10 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment Russia	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Serbia	11 Participants n=5 Participants	13 Participants n=7 Participants	24 Participants n=5 Participants
Region of Enrollment South Africa	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Spain	23 Participants n=5 Participants	25 Participants n=7 Participants	48 Participants n=5 Participants
Region of Enrollment Sweden	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Switzerland	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Turkey	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United Kingdom	20 Participants n=5 Participants	46 Participants n=7 Participants	66 Participants n=5 Participants
Region of Enrollment Argentina	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Brazil	16 Participants n=5 Participants	27 Participants n=7 Participants	43 Participants n=5 Participants
Region of Enrollment Chile	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Colombia	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Canada	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Mexico	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	36 Participants n=5 Participants	46 Participants n=7 Participants	82 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	237 Participants n=5 Participants	366 Participants n=7 Participants	603 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Denmark	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment France	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment Germany	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Greece	50 Participants n=5 Participants	63 Participants n=7 Participants	113 Participants n=5 Participants
Region of Enrollment Hungary	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Israel	5 Participants n=5 Participants	11 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment Italy	18 Participants n=5 Participants	34 Participants n=7 Participants	52 Participants n=5 Participants
Age, Continuous	72.8 years STANDARD_DEVIATION 6.77 • n=5 Participants	72.3 years STANDARD_DEVIATION 6.87 • n=7 Participants	72.5 years STANDARD_DEVIATION 6.83 • n=5 Participants
Sex: Female, Male Female	126 Participants n=5 Participants	203 Participants n=7 Participants	329 Participants n=5 Participants
Sex: Female, Male Male	155 Participants n=5 Participants	222 Participants n=7 Participants	377 Participants n=5 Participants
Race (NIH/OMB) Asian	39 Participants n=5 Participants	63 Participants n=7 Participants	102 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	15 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) White	227 Participants n=5 Participants	330 Participants n=7 Participants	557 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	15 Participants n=7 Participants	24 Participants n=5 Participants
Region of Enrollment Australia	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment China	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment Japan	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment Singapore	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Korea, Republic Of	10 Participants n=5 Participants	17 Participants n=7 Participants	27 Participants n=5 Participants
Region of Enrollment Taiwan, Province Of China	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Thailand	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Austria	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Belgium	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Czech Republic	31 Participants n=5 Participants	38 Participants n=7 Participants	69 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until PD or death (up to 52 months)

Population: ITT Population included all participants who were randomized and had post-randomization data.

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=425 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Progression Free Survival (PFS)	9.4 months Interval 8.51 to 11.47	17.4 months Interval 14.78 to 20.3

SECONDARY outcome

Timeframe: From the date of randomization and every 12 weeks after PD on next-line therapy until death (up to 88 months)

Population: ITT Population included all participants who were randomized and had post-randomization data.

OS was measured as the time from the date of randomization to the date of death.

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=425 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Overall Survival (OS)	69.5 months Interval 56.67 to 75.17	64.8 months Interval 54.87 to 74.84

SECONDARY outcome

Timeframe: Up to 27 months

Population: ITT Population included all participants who were randomized and had post-randomization data. The percentages are rounded off to the single nearest decimal point.

Response was assessed according to IMWG criteria based on IRC assessment. Best response included PR, VGPR and CR. PR= \>=50% reduction of serum M protein and \>=90% or \<200 mg reduction urinary M protein in 24-hour, or \>50% decrease in difference between involved and uninvolved FLC levels, or \>50% reduction in bone marrow plasma cells, if bone marrow plasma cells \>30% and \>50% reduction in size of soft tissue plasmacytomas at baseline. VGPR= \>90% reduction (\<100 mg/24-hour) in serum M-protein + urine M-protein detectable by immunofixation but not on electrophoresis. Complete response= \>5% plasma cells in myelogram with absence of paraprotein in serum and urine according to immunofixation.

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=425 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Percentage of Participants Who Achieve or Maintain Any Best Response Category During the Treatment Period PR	29 percentage of participants	25 percentage of participants
Percentage of Participants Who Achieve or Maintain Any Best Response Category During the Treatment Period VGPR	37 percentage of participants	34 percentage of participants
Percentage of Participants Who Achieve or Maintain Any Best Response Category During the Treatment Period CR	28 percentage of participants	31 percentage of participants

SECONDARY outcome

Timeframe: From randomization until PD or death (up to 52 months)

Population: ITT Population included all participants who were randomized and had post-randomization data.

TTP is defined as the time from the date of randomization to the date of first documentation of PD, using IMWG criteria.

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=425 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Time to Progression (TTP)	9.6 months Interval 8.67 to 11.99	17.8 months Interval 15.67 to 20.63

SECONDARY outcome

Timeframe: From the date of randomization to every 12 weeks until second PD or death (up to 88 months)

Population: ITT Population included all participants who were randomized and had post-randomization data.

PFS2 is defined as the time from the date of randomization to objective PD on next-line treatment using IMWG criteria, or death due to any cause, whichever occurred first.

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=425 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Progression Free Survival 2 (PFS2)	50.3 months Interval 40.05 to 62.46	51.3 months Interval 44.91 to 63.41

SECONDARY outcome

Timeframe: From randomization until PD or death (up to 52 months)

Population: ITT Population included all participants who were randomized and had post-randomization data.

TTNT is defined as the time from the date of randomization to the date of the first dose of next-line antineoplastic therapy.

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=425 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Time to Next Line Therapy (TTNT)	16.1 months Interval 13.54 to 19.35	22.1 months Interval 19.55 to 25.89

SECONDARY outcome

Timeframe: From randomization until PD or death (up to 52 months)

Population: ITT Population included all participants who were randomized and had post-randomization data. Overall number analyzed is the number of participants with data available for analyses.

Time to end of the next line of therapy is defined as the time from the date of randomization to the date of last dose of the next line of antineoplastic therapy following study treatment.

Outcome measures

Outcome measures
Measure	Placebo n=164 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=215 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Time to End of the Next-line of Therapy After Study Treatment	25.6 months Interval 22.7 to 28.48	23.1 months Interval 20.93 to 26.05

SECONDARY outcome

Timeframe: From randomization until PD or death (up to 52 months)

Population: ITT Population included all participants who were randomized and had post-randomization data. Overall number analyzed is the number of participants with data available for analyses.

Duration of next-line therapy is defined as the time from the date of the first dose of the next line of antineoplastic therapy coming after study treatment to the date of the last dose.

Outcome measures

Outcome measures
Measure	Placebo n=164 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=215 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Duration of Next-line Therapy	14.0 months Interval 10.41 to 16.82	8.7 months Interval 7.85 to 10.87

SECONDARY outcome

Timeframe: From randomization until PD or death (up to 52 months)

Outcome measures

Outcome measures
Measure	Placebo n=276 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=426 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Percentage of Participants Who Develop a New Primary Malignancy	6.2 percentage of participants	5.2 percentage of participants

SECONDARY outcome

Timeframe: Up to 52 months

Population: ITT Population included all participants who were randomized and had post-randomization data. Overall number analyzed is the number of participants with data available for analyses. The percentages are rounded off to the nearest single decimal point.

Bone marrow aspirates and blood samples were sent to a central laboratory and were assessed for MRD using flow cytometry. MRD negativity was defined as absence of MRD and MRD positivity was defined as presence of MRD. MRD was assessed by 8-color flow cytometry with the IMWG recommended sensitivity of 10\^-5.

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=169 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Percentage of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative	3 percentage of participants	6 percentage of participants

SECONDARY outcome

Timeframe: From randomization up to 52 months

Population: ITT Population included all participants who were randomized and had post-randomization data. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses for the specified category.

PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurred first, assessed for up to 52 months in this outcome measure. OS was measured as the time from the date of randomization to the date of death, assessed for up to 52 months in this outcome measure. Participants with various types of known MRD status were pooled together for analysis of overall survival in this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=151 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=213 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Correlation of MRD Status With PFS and OS PFS for Participants with Known MRD+ at Study Entry	9.3 months Interval 7.75 to 11.99	16.9 months Interval 13.47 to 21.29
Correlation of MRD Status With PFS and OS PFS for Participants with Known MRD- at Study Entry	NA months Interval 23.69 to Median and upper limit of confidence interval (CI) were not estimable due to censoring.	40.5 months Interval 26.94 to Upper limit of CI was not estimable due to censoring.
Correlation of MRD Status With PFS and OS OS for Participants with Known MRD Status (MRD- Status, MRD+ Status) at Study Entry	NA months Median, upper, and lower limit of CI were not estimable due to censoring.	NA months Median, upper, and lower limit of CI were not estimable due to censoring.

SECONDARY outcome

Timeframe: From the date of randomization and every 12 weeks after PD on next-line therapy until death (up to 88 months)

Population: ITT Population included all participants who were randomized and had post-randomization data. Overall number of participants analyzed is the number of participants present in the high-risk group.

High-risk population included but not be limited to participants carrying cytogenetic deletion (del)17, translocation \[t\](4;14), t(14;16). OS was measured as the time from the date of randomization to the date of death.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=74 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
OS in a High-risk Population	48.3 months Interval 29.7 to 74.48	37.3 months Interval 26.05 to 47.44

SECONDARY outcome

Timeframe: From randomization until PD or death (up to 52 months)

High-risk population included but not be limited to participants carrying del17, t(4;14), t(14;16). PFS was defined as the time from the date of randomization to the date of first documentation of PD or death from any cause.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=74 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
PFS in a High-risk Population	9.6 months Interval 5.62 to 13.9	10.1 months Interval 6.01 to 17.02

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, and 26, progression free survival follow-up (PFSFU)- Visit 37 and progressive disease follow-up (PDFU)- Visit 26 (cycle length=28 days)

Population: Safety Population included all participants who received at least 1 dose of ixazomib or placebo. Three placebo participants who erroneously received a single dose of ixazomib were included in the ixazomib arm of the safety population. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses for the specified category.

ECOG performance status assesses a participant's performance status on a 6-point scale ranging from 0=fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (\>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead. Lower grades indicate improvement.

Outcome measures

SECONDARY outcome

Timeframe: First dose of study drug through 30 days after last dose of study drug (up to 88 months)

An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAEs were defined as events that occurred after administration of the first dose of ixazomib or placebo through 30 days after the last dose of ixazomib or placebo. A SAE means any untoward medical occurrence that resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was considered medically significant.

Outcome measures

Outcome measures
Measure	Placebo n=276 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=426 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAE	82 percentage of participants	92 percentage of participants
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAE	17 percentage of participants	24 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, and 26 (cycle length=28 days)

Population: ITT Population included all participants who were randomized and had post-randomization data. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses for the specified time point.

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The change from baseline in GHS (EORTC QLQ-C30) score is presented. Participant responses to the question "How would you rate your overall health during the past week?" are scored on a 7-point scale (1=very poor to 7=excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall GHS.

Outcome measures

Outcome measures
Measure	Placebo n=257 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=391 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 2	1.7 score on a scale Standard Deviation 16.63	-0.1 score on a scale Standard Deviation 16.77
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 5	1.8 score on a scale Standard Deviation 15.79	0.6 score on a scale Standard Deviation 16.33
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 11	3.9 score on a scale Standard Deviation 17.37	0.2 score on a scale Standard Deviation 17.75
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 3	2.1 score on a scale Standard Deviation 15.74	-1.2 score on a scale Standard Deviation 17.14
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 4	1.5 score on a scale Standard Deviation 16.80	-0.6 score on a scale Standard Deviation 16.53
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 6	1.0 score on a scale Standard Deviation 18.33	-1.5 score on a scale Standard Deviation 16.56
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 7	3.1 score on a scale Standard Deviation 16.32	-0.7 score on a scale Standard Deviation 17.28
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 8	0.9 score on a scale Standard Deviation 18.07	-0.4 score on a scale Standard Deviation 17.44
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 9	1.4 score on a scale Standard Deviation 16.67	0.1 score on a scale Standard Deviation 16.57
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 10	2.0 score on a scale Standard Deviation 16.38	-1.6 score on a scale Standard Deviation 17.82
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 12	3.9 score on a scale Standard Deviation 14.53	0.3 score on a scale Standard Deviation 16.26
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 13	4.2 score on a scale Standard Deviation 16.13	-0.5 score on a scale Standard Deviation 16.85
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 14	3.1 score on a scale Standard Deviation 16.99	-1.1 score on a scale Standard Deviation 17.45
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 15	2.2 score on a scale Standard Deviation 16.74	-0.7 score on a scale Standard Deviation 17.65
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 16	2.5 score on a scale Standard Deviation 15.57	0.5 score on a scale Standard Deviation 17.03
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 17	2.4 score on a scale Standard Deviation 15.09	-0.2 score on a scale Standard Deviation 18.09
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 18	0.5 score on a scale Standard Deviation 18.40	1.7 score on a scale Standard Deviation 16.87
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 19	1.6 score on a scale Standard Deviation 18.07	1.1 score on a scale Standard Deviation 17.24
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 20	1.1 score on a scale Standard Deviation 17.95	0.4 score on a scale Standard Deviation 16.13
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 21	1.5 score on a scale Standard Deviation 16.39	1.3 score on a scale Standard Deviation 16.19
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 22	1.6 score on a scale Standard Deviation 15.55	1.0 score on a scale Standard Deviation 17.13
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 23	2.1 score on a scale Standard Deviation 19.01	0.9 score on a scale Standard Deviation 16.96
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 24	-0.3 score on a scale Standard Deviation 20.46	2.3 score on a scale Standard Deviation 15.65
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 25	0.0 score on a scale Standard Deviation 18.80	0.3 score on a scale Standard Deviation 17.52
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS) Cycle 26	2.8 score on a scale Standard Deviation 17.49	0.9 score on a scale Standard Deviation 17.26

SECONDARY outcome

Timeframe: From randomization up to 52 months

Population: ITT Population included all participants who were randomized and had post-randomization data. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis for the specified category.

Participant's frailty status is classified as fit, unfit or frail on the bases of 4 components: age, the Charlson comorbidity scoring system without age weighting, the Katz index of independence in activities of daily living, and the Lawton instrumental activities of daily living scale. The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurs first, assessed for up to 52 months in this outcome measure. OS will be measured as the time from the date of randomization to the date of death, assessed for up to 52 months in this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=112 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=172 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Correlation Between Frailty Status and PFS and OS PFS Based on Frailty Status of Fit	8.5 months Interval 7.39 to 10.41	18.6 months Interval 12.75 to 25.63
Correlation Between Frailty Status and PFS and OS PFS Based on Frailty Status of Unfit	10.6 months Interval 7.39 to 14.23	17.6 months Interval 13.17 to 21.78
Correlation Between Frailty Status and PFS and OS PFS Based on Frailty Status of Frail	11.1 months Interval 8.44 to 15.67	15.4 months Interval 11.1 to 23.75
Correlation Between Frailty Status and PFS and OS OS Based on Frailty Status of Fit	NA months Median, upper, and lower limit of CI were not estimable due to censoring.	NA months Median, upper, and lower limit of CI were not estimable due to censoring.
Correlation Between Frailty Status and PFS and OS OS Based on Frailty Status of Unfit	NA months Median, upper, and lower limit of CI were not estimable due to censoring.	NA months Interval 39.59 to Median and lower limit of CI were not estimable due to censoring.
Correlation Between Frailty Status and PFS and OS OS Based on Frailty Status of Frail	42.5 months Interval 29.93 to Upper limit of CI was not estimable due to censoring.	46.5 months Interval 34.3 to 46.52

SECONDARY outcome

Timeframe: Cycle 1 (1 and 4 hours post-dose Day 1, Days 8 and 15 pre-dose); Cycle 2 and 5 (Days 1 and 8 pre-dose) and Cycles 3, 4, 6 to 10 (Day 1 pre-dose) (cycle length=28 days)

Population: Pharmacokinetic Analysis Population included all participants with at least one pharmacokinetic (PK) sample that was collected and analyzed. Number analyzed is the number of participants with data available for analysis at the specified time point.

Plasma concentrations of the complete hydrolysis product of ixazomib citrate (ixazomib) were measured using a validated liquid chromatography-tandem mass spectrometry (LC/MS/MS) assay.

Outcome measures

Outcome measures
Measure	Placebo n=423 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 1 Day 1 - 1 Hour Post-dose	19.353 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 89.2568	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 1 Day 1 - 4 Hours Post-dose	12.698 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 67.8350	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 1 Day 8 - Pre-dose	1.683 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 162.3947	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 1 Day 15 - Pre-dose	2.828 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 86.7699	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 2 Day 1 - Pre-dose	1.958 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 170.8938	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 2 Day 8 - Pre-dose	3.217 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 188.6379	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 3 Day 1 - Pre-dose	2.252 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 56.2869	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 4 Day 1 - Pre-dose	2.363 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 52.9781	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 5 Day 1 - Pre-dose	2.328 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 53.0909	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 5 Day 8 - Pre-dose	4.547 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 224.4312	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 6 Day 1 - Pre-dose	2.503 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 52.9349	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 7 Day 1 - Pre-dose	2.585 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 57.9514	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 8 Day 1 - Pre-dose	2.606 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 58.5109	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 9 Day 1 - Pre-dose	2.566 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 58.1094	—
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib Cycle 10 Day 1 - Pre-dose	2.686 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 50.2494	—

SECONDARY outcome

Timeframe: Up to 52 months

Population: Safety Population included all participants who received at least 1 dose of ixazomib or placebo. Overall number of participants analyzed are the number of participants with events.

PN is defined as the event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the medical dictionary for regulatory activities (MedDRA). A PN event was considered as resolved if its final outcome was resolved with no subsequent PN event of the same preferred term occurring on the resolution date or the day before and after. Time to resolution was defined as the time from the initial onset date (inclusive) to the resolution date for resolved events.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=83 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Time to Resolution of Peripheral Neuropathy (PN) Events	196.0 days Interval 43.0 to 331.0	451.0 days Interval 98.0 to Upper limit of CI was not estimable due to censoring.

SECONDARY outcome

Timeframe: Up to 52 months

Population: Safety Population included all participants who received at least 1 dose of ixazomib or placebo. Overall number of participants analyzed are the number of participants with events.

PN is defined as the event in the high-level term of peripheral neuropathies NEC according to the MedDRA. A PN event was considered as resolved if its final outcome was resolved with no subsequent PN event of the same preferred term occurring on the improvement date or the day before and after. Time to improvement was defined as the time from the initial onset date (inclusive) to the improvement of event.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=83 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Time to Improvement of PN Events	81.0 days Interval 15.0 to 280.0	64.0 days Interval 29.0 to 393.0

Adverse Events

Placebo

Serious events: 48 serious events

Other events: 188 other events

Deaths: 115 deaths

Ixazomib

Serious events: 101 serious events

Other events: 340 other events

Deaths: 184 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=271 Participants Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26.	Ixazomib n=415 Participants Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26.
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 6 Day 1	-0.0 score on a scale Standard Deviation 0.46	-0.0 score on a scale Standard Deviation 0.43
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 13 Day 1	-0.0 score on a scale Standard Deviation 0.54	-0.0 score on a scale Standard Deviation 0.46
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 2 Day 1	-0.0 score on a scale Standard Deviation 0.36	-0.0 score on a scale Standard Deviation 0.42
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 3 Day 1	-0.0 score on a scale Standard Deviation 0.36	-0.0 score on a scale Standard Deviation 0.42
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 4 Day 1	-0.0 score on a scale Standard Deviation 0.39	-0.1 score on a scale Standard Deviation 0.42
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 5 Day 1	-0.0 score on a scale Standard Deviation 0.44	-0.0 score on a scale Standard Deviation 0.44
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 7 Day 1	-0.0 score on a scale Standard Deviation 0.49	-0.0 score on a scale Standard Deviation 0.42
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 8 Day 1	-0.1 score on a scale Standard Deviation 0.48	-0.0 score on a scale Standard Deviation 0.42
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 9 Day 1	-0.1 score on a scale Standard Deviation 0.47	-0.0 score on a scale Standard Deviation 0.45
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 10 Day 1	-0.1 score on a scale Standard Deviation 0.52	-0.0 score on a scale Standard Deviation 0.47
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 11 Day 1	-0.1 score on a scale Standard Deviation 0.51	-0.0 score on a scale Standard Deviation 0.43
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 12 Day 1	-0.1 score on a scale Standard Deviation 0.56	-0.0 score on a scale Standard Deviation 0.43
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 14 Day 1	0.0 score on a scale Standard Deviation 0.53	-0.0 score on a scale Standard Deviation 0.44
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 15 Day 1	-0.0 score on a scale Standard Deviation 0.53	-0.0 score on a scale Standard Deviation 0.49
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 16 Day 1	-0.0 score on a scale Standard Deviation 0.51	-0.0 score on a scale Standard Deviation 0.49
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 17 Day 1	-0.0 score on a scale Standard Deviation 0.54	-0.0 score on a scale Standard Deviation 0.50
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 18 Day 1	0.0 score on a scale Standard Deviation 0.51	-0.0 score on a scale Standard Deviation 0.51
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 19 Day 1	0.0 score on a scale Standard Deviation 0.47	-0.0 score on a scale Standard Deviation 0.49
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 20 Day 1	0.0 score on a scale Standard Deviation 0.46	-0.0 score on a scale Standard Deviation 0.49
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 21 Day 1	0.0 score on a scale Standard Deviation 0.48	-0.0 score on a scale Standard Deviation 0.52
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 22 Day 1	0.1 score on a scale Standard Deviation 0.51	-0.0 score on a scale Standard Deviation 0.52
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 23 Day 1	0.0 score on a scale Standard Deviation 0.44	-0.0 score on a scale Standard Deviation 0.48
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 24 Day 1	0.1 score on a scale Standard Deviation 0.54	-0.0 score on a scale Standard Deviation 0.47
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 25 Day 1	0.0 score on a scale Standard Deviation 0.42	-0.0 score on a scale Standard Deviation 0.47
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Cycle 26 Day 1	0.0 score on a scale Standard Deviation 0.47	-0.0 score on a scale Standard Deviation 0.47
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status PFSFU- Visit 37	—	1.0 score on a scale Standard Deviation NA Standard deviation was not estimable for a single participant.
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status PDFU- Visit 26	—	1.0 score on a scale Standard Deviation NA Standard deviation was not estimable for a single participant.