Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma. (CANDOR)

• ClinicalTrials.gov Identifier: NCT03158688
• Recruitment Status: Completed
• First Posted: May 18, 2017
• Results First Posted: September 11, 2020
• Last Update Posted: March 5, 2024
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Relapsed Multiple Myeloma; Refractory Multiple Myeloma
• Interventions: Drug: Dexamethasone; Drug: Daratumumab; Drug: Carfilzomib
• Enrollment: 466

Participant Flow

Recruitment Details	This study was conducted at 102 centers. 569 participants were screened and 466 were enrolled. Primary analysis (PA) data cutoff (DCO): 14-Jul-2019. Final analysis (FA) DCO: 15-Apr-2022.
Pre-assignment Details	Participants were randomized in 1:2 ratio to arms KD vs KdD after being stratified by 1) International Staging System (ISS) stage (Stage 1-2 vs Stage 3) at screening, 2) prior proteasome inhibitor exposure (yes/no), 3) number of prior lines of therapy (1 vs ≥ 2), and 4) prior cluster differentiation antigen 38 (CD38) antibody therapy (yes/no).

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Period Title: Overall Study
Started	154	312
Treated	153	308
Completed	49	102
Not Completed	105	210
Reason Not Completed
Withdrawal by Subject	14	28
Decision by sponsor	13	37
Lost to Follow-up	4	3
Death	74	142

Baseline Characteristics

Arm/Group Title		Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab	Total
Arm/Group Description		Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.	Total of all reporting groups
Overall Number of Baseline Participants		154	312	466
Baseline Analysis Population Description		Intent to Treat population
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	154 participants	312 participants	466 participants
		64.3 (9.6)	62.9 (10.0)	63.4 (9.9)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	312 participants	466 participants
	18 - 64 years	77 50.0%	163 52.2%	240 51.5%
	65 - 74 years	55 35.7%	121 38.8%	176 37.8%
	75 - 84 years	22 14.3%	28 9.0%	50 10.7%
	>=85 years	0 0.0%	0 0.0%	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	312 participants	466 participants
	Female	63 40.9%	135 43.3%	198 42.5%
	Male	91 59.1%	177 56.7%	268 57.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	312 participants	466 participants
	Hispanic or Latino	1 0.6%	7 2.2%	8 1.7%
	Not Hispanic or Latino	146 94.8%	291 93.3%	437 93.8%
	Unknown or Not Reported	7 4.5%	14 4.5%	21 4.5%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	312 participants	466 participants
	Asian	20 13.0%	46 14.7%	66 14.2%
	Black or African American	2 1.3%	7 2.2%	9 1.9%
	White	123 79.9%	243 77.9%	366 78.5%
	Other	9 5.8%	16 5.1%	25 5.4%
Frailty Status as Assessed by Investigator; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	312 participants	466 participants
	Fit	68 44.2%	176 56.4%	244 52.4%
	Intermediate fitness	36 23.4%	54 17.3%	90 19.3%
	Frail	9 5.8%	10 3.2%	19 4.1%
	Not available	37 24.0%	66 21.2%	103 22.1%
	Missing	4 2.6%	6 1.9%	10 2.1%
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	312 participants	466 participants
	Disease status 0 or 1	147 95.5%	295 94.6%	442 94.8%
	Disease status 2	7 4.5%	15 4.8%	22 4.7%
	Missing	0 0.0%	2 0.6%	2 0.4%
		[1] Measure Description: A scale to assess a patient's disease status. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2 = Ambulatory and capable of all self care, unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.
Time from Initial Diagnosis to Randomization [1]; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	149 participants	297 participants	446 participants
		44.03 (36.57)	47.86 (34.69)	46.58 (35.34)
		[1] Measure Analysis Population Description: Data was not available for some participants.
Risk Group as Determined by Fluorescent in situ Hybridization (FISH) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	312 participants	466 participants
	High risk	26 16.9%	48 15.4%	74 15.9%
	Standard risk	56 36.4%	108 34.6%	164 35.2%
	Unknown	72 46.8%	156 50.0%	228 48.9%
		[1] Measure Description: The high-risk group consists of the genetic subtypes t(4; 14), t(14; 16), or deletion17p. The standard-risk group consists of participants without t(4; 14), t(14; 16), and deletion 17p. The unknown risk group is participants with FISH result not done, failed or quantity was not sufficient.
Stratification Factor: International Staging System (ISS) Stage per IxRS [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	312 participants	466 participants
	Stage I or II	127 82.5%	252 80.8%	379 81.3%
	Stage III	27 17.5%	60 19.2%	87 18.7%
		[1] Measure Description: The International Staging System (ISS) for myeloma was published by the International Myeloma Working Group (a lower stage indicates less progressed disease): Stage I: β2-microglobulin (β2M) < 3.5 mg/L, albumin >= 3.5 g/dL Stage II: β2M < 3.5 mg/L and albumin < 3.5 g/dL; or β2M 3.5 mg/L - 5.5 mg/L irrespective of the serum albumin Stage III: β2M ≥ 5.5 mg/L. Higher stages indicate more advanced disease and/or poorer prognosis. Data is the ISS result assessed at the time of randomization using an interactive voice/web response system (IxRS).
Stratification Factor: Lines of Prior Treatment per IxRS [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	312 participants	466 participants
	1 prior treatment	67 43.5%	133 42.6%	200 42.9%
	> = 2 prior treatments	87 56.5%	179 57.4%	266 57.1%
		[1] Measure Description: Number of participants grouped by total number of prior regimens. Data reported are randomization stratification values.
Stratification Factor: Prior Proteasome Inhibitor Treatment per IxRS [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	312 participants	466 participants
	Yes	139 90.3%	279 89.4%	418 89.7%
	No	15 9.7%	33 10.6%	48 10.3%
		[1] Measure Description: The number of participants with prior proteasome inhibitor treatment assessed at the time of randomization per the IxRS. Data reported are randomization stratification values.
Stratification Factor: Prior CD38 Antibody Therapy per IxRS [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	312 participants	466 participants
	Yes	0 0.0%	1 0.3%	1 0.2%
	No	154 100.0%	311 99.7%	465 99.8%
		[1] Measure Description: The number of participants with prior CD38 antibody therapy assessed at the time of randomization per the IxRS. Data reported are randomization stratification values.
Geographic Regions; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	312 participants	466 participants
	North America	12 7.8%	21 6.7%	33 7.1%
	Europe	103 66.9%	207 66.3%	310 66.5%
	Asia Pacific	39 25.3%	84 26.9%	123 26.4%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) as Assessed by the Independent Review Committee (PA DCO Only)
Description	Progression-free survival (PFS) was defined as the time from randomization to the earlier of disease progression or death due to any cause. Participants were evaluated for disease response and progression according to the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) as assessed by an Independent Review Committee (IRC). The duration of PFS was right censored for participants who met any of the following conditions: 1. no baseline/post-baseline disease assessments; 2. started a new anti myeloma therapy before documentation of progressive disease or death; 3. progressive disease or death immediately after more than 70 days without disease assessment visit or; 4. alive without documentation of disease progression before the analysis trigger date (PA DCO); 5. lost to follow-up or withdrawn consent.
Time Frame	From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	154	312
Measure Type: Count of Participants; Unit of Measure: Participants
Participants with PFS events	68 44.2%	110 35.3%
Participants who were censored	86 55.8%	202 64.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kd - Carfilzomib and Dexamethasone, KdD - Carfilzomib, Dexamethasone and Daratumumab
	Comments	Stratification factors used in the Log-rank p-value (1-sided) and the Cox model hazard ratio (KdD/Kd) were as assessed at randomization: International Staging System stage at screening (Stage 1 or 2 vs Stage 3); prior proteasome inhibitor exposure (yes vs no); number of prior lines of therapy (1 vs >= 2).
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0014
	Comments	alpha level of 0.025
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Stratified Cox model hazard ratio
	Estimated Value	0.630
	Confidence Interval	(2-Sided) 95%; 0.464 to 0.854
	Estimation Comments	KdD/Kd

2. Secondary Outcome

Title	Overall Response (OR) as Assessed by the Independent Review Committee (PA DCO Only)
Description	Overall response rate was defined as the percentage of participants in each treatment group who achieve partial response (PR) or better per the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) as their best response. Complete Response (CR): No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-component with urine M-component <100 mg/24 hours. Partial Response (PR): ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to < 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline. 95% CIs for proportions were estimated using the Clopper-Pearson method.
Time Frame	From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	154	312
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	74.7; (67.0 to 81.3)	84.3; (79.8 to 88.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kd - Carfilzomib and Dexamethasone, KdD - Carfilzomib, Dexamethasone and Daratumumab
	Comments	Odds ratios and corresponding 95% CIs were estimated using the stratified Mantel-Haenszel method. P-values were calculated using the stratified Cochran-Mantel-Haenszel Chi-Square test.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0040
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.925
	Confidence Interval	(2-Sided) 95%; 1.184 to 3.129
	Estimation Comments	KdD/Kd

3. Secondary Outcome

Title	Minimal Residual Disease Negative Complete Response Rate (MRD[-]CR) at 12 Months as Assessed by the Independent Review Committee
Description	MRD[-]CR at 12 months was defined as achievement of CR per IMWG-URC by IRC and MRD[-] status as assessed by next-generation sequencing (NGS; at a 10^-5 level) at the 12 months landmark (8 to 13 month window).
Time Frame	12 Months (8- to 13-month window)

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	154	312
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	1.9; (0.4 to 5.6)	12.8; (9.3 to 17.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kd - Carfilzomib and Dexamethasone, KdD - Carfilzomib, Dexamethasone and Daratumumab
	Comments	Odds ratios and corresponding 95% CIs were estimated using the stratified Mantel-Haenszel method.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.819
	Confidence Interval	(2-Sided) 95%; 2.364 to 25.858
	Estimation Comments	KdD/Kd

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from randomization until death from any cause. Deaths collected via public source, after end of study were included. Medians were estimated using the Kaplan-Meier method. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. Participants still alive were censored at the date last known to be alive.
Time Frame	Up to 58 months after the first participant was enrolled (at FA DCO, a median of 40.29 weeks of treatment [any study drug] in the Kd group and 79.29 weeks of treatment [any study drug] in the KdD group; FA DCO was 15 Apr 2022)

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	154	312
Median (95% Confidence Interval); Unit of Measure: months
	43.6 [1]; (35.3 to NA)	50.8 [1]; (44.7 to NA)

[1]

Not enough events to estimate the upper 95% CI

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kd - Carfilzomib and Dexamethasone, KdD - Carfilzomib, Dexamethasone and Daratumumab
	Comments	Hazard ratio and corresponding 95% CIs were estimated using the stratified Cox proportional hazards models. 1-sided p-value from the log-rank test controlling for the randomization stratification factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0417
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.784
	Confidence Interval	(2-Sided) 95%; 0.595 to 1.033
	Estimation Comments	KdD/Kd

5. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	Treatment-emergent adverse events are defined as any adverse event with an onset after the administration of the first dose of any study treatment and within the end of study or 30 days of the last dose of any study treatment, whichever occurs earlier. The severity of adverse events was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal. Treatment-related adverse events are treatment-emergent adverse events considered related to at least one study drug by the investigator, including those with unknown relationship.
Time Frame	PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	153	308
Measure Type: Count of Participants; Unit of Measure: Participants
PA DCO: All TEAEs	147 96.1%	306 99.4%
PA DCO: TEAEs: Severity Grade >=3	113 73.9%	253 82.1%
PA DCO: TEAEs: Serious Adverse Events	70 45.8%	173 56.2%
PA DCO: TEAEs: Leading to discon of carfilzomib	33 21.6%	65 21.1%
PA DCO: TEAEs: Leading to discon of daratumumab	NA [1]	28 9.1%
PA DCO: TEAEs: Leading to discon of dexamethasone	37 24.2%	33 10.7%
PA DCO: Fatal TEAEs	8 5.2%	30 9.7%
PA DCO: Treatment-related TEAEs	129 84.3%	260 84.4%
PA DCO: Related TEAEs: Grade >=3	74 48.4%	187 60.7%
PA DCO: Related and serious TEAEs	32 20.9%	84 27.3%
PA DCO: Related TEAEs: discon of carfilzomib	21 13.7%	50 16.2%
PA DCO: Related TEAEs: discon of daratumumab	NA [1]	15 4.9%
PA DCO: Related TEAEs: discon of dexamethasone	24 15.7%	19 6.2%
PA DCO: Related Fatal TEAEs	0 0.0%	5 1.6%
FA DCO: All TEAEs	149 97.4%	306 99.4%
FA DCO: TEAEs: Severity Grade >=3	120 78.4%	273 88.6%
FA DCO: TEAEs: Serious Adverse Events	80 52.3%	211 68.5%
FA DCO: TEAEs: Leading to discontinuation of carfilzomib	37 24.2%	98 31.8%
FA DCO: TEAEs: Leading to discontinuation of daratumumab	NA [1]	43 14.0%
FA DCO: TEAEs: Leading to discon of dexamethasone	40 26.1%	58 18.8%
FA DCO: Fatal TEAEs	11 7.2%	39 12.7%
FA DCO: Treatment-related TEAEs	131 85.6%	267 86.7%
FA DCO: Related TEAEs: Grade >=3	82 53.6%	206 66.9%
FA DCO: Related and serious TEAEs	34 22.2%	102 33.1%
FA DCO: Related TEAEs: discon of carfilzomib	22 14.4%	69 22.4%
FA DCO: Related TEAEs: discon of daratumumab	NA [1]	18 5.8%
FA DCO: Related TEAEs: discon of dexamethasone	24 15.7%	30 9.7%
FA DCO: Related Fatal TEAEs	0 0.0%	5 1.6%

[1]

not relevant for this treatment arm

6. Secondary Outcome

Title	Kaplan-Meier Estimate for Duration of Response (DOR) (PA DCO Only)
Description	Duration of response (DOR) was defined as the time (in months) from first evidence of partial response (PR) or better per IMWG-URC by IRC to the earlier of disease progression or death due to any cause for participants with a best response of PR or better. For those who are alive and have not experienced disease progression at the time of data cutoff for analysis, duration of response was right-censored. Medians were estimated using the Kaplan-Meier method. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.
Time Frame	From Day 1 until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Outcome Measure Data

Analysis Population Description

Participants who responded in the Intent to Treat Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	115	263
Median (95% Confidence Interval); Unit of Measure: months
	16.6 [1]; (13.9 to NA)	NA [2]; (NA to NA)

[1]

Not enough events to estimate the upper 95% CI

[2]

Not enough events to estimate a median and confidence intervals

7. Secondary Outcome

Title	Kaplan-Meier Estimate for Time to Next Treatment (TTNT)
Description	Time to next treatment was defined as the time (in months) from randomization to the initiation of subsequent non-protocol anti-cancer treatment for multiple myeloma. Time to next treatment for participants who do not start the subsequent treatment for multiple myeloma was censored at the date when the participant's information was last available. Medians of TTNT duration were estimated using the Kaplan-Meier method. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.
Time Frame	PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	154	312
Median (95% Confidence Interval); Unit of Measure: months
PA DCO	17.3 [1]; (13.5 to NA)	NA [2]; (NA to NA)
FA DCO	17.8; (13.5 to 23.1)	37.4; (30.1 to 47.8)

[1]

Not enough events to estimate the upper 95% CI

[2]

Not enough events to estimate a median and confidence intervals

8. Secondary Outcome

Title	Kaplan-Meier Estimates for Time to Progression (TTP) as Assessed by the Independent Review Committee (PA DCO Only)
Description	Time to progression was defined as the time (in months) from randomization to documented disease progression. Participants who did not have documented disease progression were censored at the date when data was last available.
Time Frame	From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	154	312
Median (95% Confidence Interval); Unit of Measure: months
	17.5 [1]; (13.2 to NA)	NA [2]; (NA to NA)

[1]

Not enough events to estimate the upper 95% CI

[2]

Not enough events to estimate a median and confidence intervals

9. Secondary Outcome

Title	Time to Progression (TTP): Percentage of Participants Who Had Not Had Disease Progression as Assessed by the Independent Review Committee at Months 3, 6, 12, and 18 (PA DCO Only)
Description	Time to progression was defined as the time (in months) from randomization to documented disease progression. This outcome reports TTP as the percentage of participants who were event free (that is, they had not had disease progression) at the specified time frames. Independent Review Committee assessment for this outcome measure was not planned after the primary analysis. 95% CIs for event-free rates were estimated using the method by Kalbfleisch and Prentice (1980) with log-log transformation.
Time Frame	Randomization to Months 3, 6, 12, and 18

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	154	312
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
3 months	90.0; (83.7 to 93.9)	95.3; (92.1 to 97.2)
6 months	79.4; (71.6 to 85.3)	86.4; (81.8 to 89.9)
12 months	62.7; (53.6 to 70.5)	77.5; (72.1 to 82.0)
18 months	45.1; (34.5 to 55.4)	68.5; (62.2 to 74.0)

10. Secondary Outcome

Title	Time to Overall Response as Assessed by the Independent Review Committee (PA DCO Only)
Description	Time to overall response was defined as the time from randomization to the earliest date a response of partial response (PR) or better as per IMWG-URC is first achieved and subsequently confirmed for participants with a best response of PR or better.
Time Frame	From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Outcome Measure Data

Analysis Population Description

Participants who responded in the Intent to Treat Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	115	263
Mean (Standard Deviation); Unit of Measure: months
	1.5 (1.1)	1.4 (1.4)

11. Secondary Outcome

Title	Percentage of Participants Who Achieved and Maintained a Minimal Residual Disease Negative Complete Response (MRD[-]CR) for 12 Months or More
Description	A measure of the persistence of the CR (includes strict CR) per International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) and MRD[-] status as assessed by next-generation sequencing (NGS; at a 10^-5 level) for 12 months or more after achieving MRD[-]CR status. 95% confidence intervals (CIs) for proportions were estimated using the Clopper-Pearson method.
Time Frame	PA DCO: the longest treatment duration as of the PA DCO was 102.3 weeks; FA DCO: the longest treatment duration as of the FA DCO was 236.3 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	154	312
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
PA DCO	0.0; (0.0 to 2.4)	0.0; (0.0 to 1.2)
FA DCO	0.0; (0.0 to 2.4)	5.8; (3.5 to 9.0)

12. Secondary Outcome

Title	Percentage of Participants With a Complete Response (CR) as Assessed by the Independent Review Committee (PA DCO Only)
Description	The percentage of participants in each treatment group who achieved stringent complete response (sCR) or CR per IMWG-URC, as assessed by the IRC, as their best response is presented.
Time Frame	From randomization until the PA DCO date of 14 July 2019; the longest treatment duration as of the DCO was 102.3 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	154	312
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	10.4; (6.1 to 16.3)	28.5; (23.6 to 33.9)

13. Secondary Outcome

Title	Percentage of Participants Who Achieved Minimal Residual Disease Negative (MRD[-]) Status as Assessed by Next Generation Sequencing at 12 Months
Description	MRD[-] at 12-month was defined as achievement of MRD[-] status as assessed by next-generation sequencing (NGS; at a 10^-5 level) at the 12 months landmark (from 8 months to 13 months window). 95% confidence intervals (CIs) for proportions were estimated using the Clopper-Pearson method.
Time Frame	12 Months (8- to 13-month window)

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed	154	312
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	5.2; (2.3 to 10.0)	18.3; (14.1 to 23.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kd - Carfilzomib and Dexamethasone, KdD - Carfilzomib, Dexamethasone and Daratumumab
	Comments	Odds ratios and corresponding 95% CIs were estimated by a stratified analysis using the Mantel-Haenszel method.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.403
	Confidence Interval	(2-Sided) 95%; 2.007 to 9.656
	Estimation Comments	KdD/Kd

14. Secondary Outcome

Title	Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores For Baseline Up to the First Follow-Up Visit After the Last Dose
Description	Health-related quality of life was assessed with the use of the European Organization for Research and Treatment of Cancer Quality of Life Core Module (QLQ-C30) questionnaire, a validated instrument in multiple myeloma patients. Scores range from 0 to 100, with higher scores indicating better health related quality of life. QLQ-C30 questionnaire was administered prior to dosing every 28 ± 7 days starting from cycle 1 day 1 through first follow-up visit (30 days [+3] after last dose of all study drugs).
Time Frame	Baseline (Day 1 pre-dose) up to 236.3 weeks (longest treatment duration as of the FA DCO)

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title		Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description:		Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
Overall Number of Participants Analyzed		154	312
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	Number Analyzed	139 participants	289 participants
		66.19 (19.19)	61.79 (20.37)
Cycle 2	Number Analyzed	126 participants	281 participants
		64.35 (16.25)	61.00 (19.65)
Cycle 3	Number Analyzed	124 participants	264 participants
		66.13 (18.12)	63.10 (18.24)
Cycle 4	Number Analyzed	112 participants	258 participants
		66.67 (15.01)	63.47 (18.66)
Cycle 5	Number Analyzed	105 participants	252 participants
		67.62 (17.19)	64.45 (16.76)
Cycle 6	Number Analyzed	96 participants	244 participants
		68.06 (15.80)	65.92 (16.85)
Cycle 7	Number Analyzed	94 participants	223 participants
		69.33 (14.68)	65.73 (16.59)
Cycle 8	Number Analyzed	87 participants	206 participants
		69.44 (17.82)	66.34 (16.64)
Cycle 9	Number Analyzed	79 participants	202 participants
		65.72 (15.90)	67.82 (15.53)
Cycle 10	Number Analyzed	73 participants	197 participants
		68.38 (14.56)	67.98 (16.26)
Cycle 11	Number Analyzed	66 participants	189 participants
		67.42 (15.24)	68.52 (17.37)
Cycle 12	Number Analyzed	65 participants	187 participants
		65.13 (14.94)	67.47 (17.16)
Cycle 13	Number Analyzed	61 participants	175 participants
		67.49 (16.51)	67.00 (18.21)
Cycle 14	Number Analyzed	59 participants	169 participants
		67.66 (17.03)	66.12 (16.60)
Cycle 15	Number Analyzed	53 participants	167 participants
		69.34 (15.31)	67.61 (17.68)
Cycle 16	Number Analyzed	54 participants	165 participants
		68.21 (16.44)	66.41 (18.69)
Cycle 17	Number Analyzed	54 participants	159 participants
		69.44 (14.92)	69.81 (15.28)
Cycle 18	Number Analyzed	52 participants	155 participants
		66.67 (16.50)	66.29 (16.38)
Cycle 19	Number Analyzed	47 participants	150 participants
		69.68 (17.50)	68.00 (17.33)
Cycle 20	Number Analyzed	40 participants	141 participants
		71.04 (14.49)	66.43 (19.52)
Cycle 21	Number Analyzed	39 participants	143 participants
		70.94 (15.87)	67.42 (16.25)
Cycle 22	Number Analyzed	36 participants	139 participants
		68.52 (12.30)	67.51 (17.90)
Cycle 23	Number Analyzed	35 participants	131 participants
		69.52 (16.41)	66.67 (17.63)
Cycle 24	Number Analyzed	35 participants	125 participants
		68.10 (18.24)	68.00 (16.51)
Cycle 25	Number Analyzed	33 participants	127 participants
		67.93 (16.15)	66.21 (16.78)
Cycle 26	Number Analyzed	33 participants	121 participants
		70.71 (18.65)	66.12 (17.54)
Cycle 27	Number Analyzed	29 participants	112 participants
		65.23 (14.78)	66.52 (18.35)
Cycle 28	Number Analyzed	29 participants	109 participants
		63.22 (19.61)	67.28 (18.66)
Cycle 29	Number Analyzed	25 participants	105 participants
		66.67 (19.25)	67.22 (18.10)
Cycle 30	Number Analyzed	24 participants	104 participants
		67.01 (17.63)	67.23 (18.52)
Cycle 31	Number Analyzed	24 participants	101 participants
		68.06 (16.24)	67.33 (18.81)
Cycle 32	Number Analyzed	23 participants	94 participants
		66.67 (19.62)	67.91 (18.45)
Cycle 33	Number Analyzed	23 participants	91 participants
		67.75 (15.35)	67.95 (18.92)
Cycle 34	Number Analyzed	22 participants	86 participants
		68.18 (15.78)	69.86 (17.77)
Cycle 35	Number Analyzed	22 participants	88 participants
		65.91 (15.62)	69.51 (18.00)
Cycle 36	Number Analyzed	23 participants	86 participants
		63.77 (18.22)	68.22 (16.93)
Cycle 37	Number Analyzed	20 participants	89 participants
		67.50 (18.91)	68.63 (19.01)
Cycle 38	Number Analyzed	17 participants	84 participants
		65.20 (18.69)	69.25 (18.47)
Cycle 39	Number Analyzed	17 participants	78 participants
		64.71 (15.46)	68.38 (19.15)
Cycle 40	Number Analyzed	14 participants	78 participants
		58.33 (14.25)	67.74 (19.34)
Cycle 41	Number Analyzed	14 participants	79 participants
		66.07 (13.26)	68.46 (19.37)
Cycle 42	Number Analyzed	14 participants	68 participants
		63.69 (15.19)	67.16 (18.77)
Cycle 43	Number Analyzed	15 participants	57 participants
		67.22 (15.89)	63.30 (19.91)
Cycle 44	Number Analyzed	12 participants	50 participants
		61.81 (15.27)	65.50 (18.21)
Cycle 45	Number Analyzed	9 participants	41 participants
		67.59 (12.11)	66.87 (15.53)
Cycle 46	Number Analyzed	8 participants	34 participants
		64.58 (13.91)	67.89 (17.66)
Cycle 47	Number Analyzed	4 participants	27 participants
		66.67 (0.00)	68.52 (13.74)
Cycle 48	Number Analyzed	3 participants	22 participants
		61.11 (9.62)	68.56 (13.35)
Cycle 49	Number Analyzed	3 participants	19 participants
		61.11 (9.62)	68.42 (13.49)
Cycle 50	Number Analyzed	3 participants	16 participants
		61.11 (9.62)	68.75 (13.09)
Cycle 51	Number Analyzed	3 participants	12 participants
		63.89 (4.81)	67.36 (11.49)
Cycle 52	Number Analyzed	2 participants	9 participants
		54.17 (17.68)	62.04 (17.24)
Cycle 53	Number Analyzed	0 participants	3 participants
			61.11 (9.62)
Follow-up	Number Analyzed	25 participants	32 participants
		61.00 (23.04)	59.90 (18.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kd - Carfilzomib and Dexamethasone, KdD - Carfilzomib, Dexamethasone and Daratumumab
	Comments	Analysis was performed based on a linear mixed effects model. The model included fixed effects of treatment (all baseline responses were modeled with a dummy treatment), baseline QLQ-C30 GHS/QoL score, randomization stratification factors (ISS stage at screening (Stage 1 or 2 vs Stage 3), prior proteasome inhibitor exposure (yes vs no), number of prior lines of therapy (1 vs ≥ 2)), interaction between treatment and time, and random effects of participant intercept and random slope of time.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9480
	Comments	[Not Specified]
	Method	linear mixed effects model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -2.52 to 2.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.24
	Estimation Comments	The overall treatment difference (KdD - Kd)

Adverse Events

Time Frame	Treatment-emergent adverse events - any adverse events with an onset after the administration of the first dose of any study treatment and within the end of the study or 30 days of the last dose of any study treatment, whichever occurred earlier. The longest treatment duration as of the FA DCO was 236.3 weeks.
Adverse Event Reporting Description	All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Arm/Group Title	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
Arm/Group Description	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.	Carfilzomib was administered intravenously (IV) at 20 mg/m^2 in Cycle 1: days 1 and 2; at 56 mg/m^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg dosage was continued on Cycles 7+: day 1 only.
All-Cause Mortality
	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	80/154 (51.95%)	148/312 (47.44%)
Serious Adverse Events
	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	80/153 (52.29%)	211/308 (68.51%)
Blood and lymphatic system disorders
Anaemia † 1	1/153 (0.65%)	8/308 (2.60%)
Febrile neutropenia † 1	1/153 (0.65%)	2/308 (0.65%)
Pancytopenia † 1	1/153 (0.65%)	0/308 (0.00%)
Plasmacytosis † 1	0/153 (0.00%)	1/308 (0.32%)
Thrombocytopenia † 1	1/153 (0.65%)	5/308 (1.62%)
Thrombotic thrombocytopenic purpura † 1	2/153 (1.31%)	2/308 (0.65%)
Thrombotic microangiopathy † 1	1/153 (0.65%)	0/308 (0.00%)
Cardiac disorders
Acute coronary syndrome † 1	1/153 (0.65%)	2/308 (0.65%)
Acute myocardial infarction † 1	1/153 (0.65%)	4/308 (1.30%)
Angina pectoris † 1	2/153 (1.31%)	1/308 (0.32%)
Arteriosclerosis coronary artery † 1	1/153 (0.65%)	0/308 (0.00%)
Arteriospasm coronary † 1	0/153 (0.00%)	1/308 (0.32%)
Atrial fibrillation † 1	1/153 (0.65%)	5/308 (1.62%)
Atrial flutter † 1	0/153 (0.00%)	2/308 (0.65%)
Cardiac arrest † 1	0/153 (0.00%)	3/308 (0.97%)
Cardiac failure † 1	4/153 (2.61%)	4/308 (1.30%)
Cardiac failure acute † 1	2/153 (1.31%)	2/308 (0.65%)
Cardiac failure congestive † 1	1/153 (0.65%)	1/308 (0.32%)
Cardio-respiratory arrest † 1	0/153 (0.00%)	2/308 (0.65%)
Cardiomyopathy † 1	0/153 (0.00%)	1/308 (0.32%)
Coronary artery disease † 1	0/153 (0.00%)	1/308 (0.32%)
Extrasystoles † 1	1/153 (0.65%)	0/308 (0.00%)
Myocardial infarction † 1	1/153 (0.65%)	2/308 (0.65%)
Myocardial ischaemia † 1	0/153 (0.00%)	4/308 (1.30%)
Tachycardia † 1	0/153 (0.00%)	1/308 (0.32%)
Arrhythmia † 1	0/153 (0.00%)	1/308 (0.32%)
Atrial enlargement † 1	0/153 (0.00%)	1/308 (0.32%)
Microvascular coronary artery disease † 1	0/153 (0.00%)	1/308 (0.32%)
Stress cardiomyopathy † 1	1/153 (0.65%)	0/308 (0.00%)
Endocrine disorders
Thyroid mass † 1	1/153 (0.65%)	0/308 (0.00%)
Eye disorders
Cataract † 1	3/153 (1.96%)	9/308 (2.92%)
Gastrointestinal disorders
Abdominal pain † 1	1/153 (0.65%)	0/308 (0.00%)
Colitis † 1	1/153 (0.65%)	0/308 (0.00%)
Diarrhoea † 1	1/153 (0.65%)	8/308 (2.60%)
Diverticular perforation † 1	0/153 (0.00%)	1/308 (0.32%)
Gastritis † 1	0/153 (0.00%)	1/308 (0.32%)
Inguinal hernia † 1	0/153 (0.00%)	1/308 (0.32%)
Intra-abdominal haemorrhage † 1	1/153 (0.65%)	0/308 (0.00%)
Rectal haemorrhage † 1	1/153 (0.65%)	0/308 (0.00%)
Upper gastrointestinal haemorrhage † 1	0/153 (0.00%)	2/308 (0.65%)
Gastrointestinal disorder † 1	1/153 (0.65%)	0/308 (0.00%)
Haemorrhoids † 1	0/153 (0.00%)	1/308 (0.32%)
Melaena † 1	1/153 (0.65%)	0/308 (0.00%)
Umbilical hernia † 1	1/153 (0.65%)	0/308 (0.00%)
General disorders
Asthenia † 1	0/153 (0.00%)	1/308 (0.32%)
Chest pain † 1	1/153 (0.65%)	1/308 (0.32%)
Death † 1	1/153 (0.65%)	1/308 (0.32%)
Fatigue † 1	0/153 (0.00%)	3/308 (0.97%)
Hyperthermia † 1	0/153 (0.00%)	1/308 (0.32%)
Malaise † 1	0/153 (0.00%)	1/308 (0.32%)
Peripheral swelling † 1	1/153 (0.65%)	0/308 (0.00%)
Pyrexia † 1	4/153 (2.61%)	14/308 (4.55%)
Sudden death † 1	0/153 (0.00%)	2/308 (0.65%)
Unevaluable event † 1	0/153 (0.00%)	1/308 (0.32%)
Facial pain † 1	0/153 (0.00%)	1/308 (0.32%)
Oedema peripheral † 1	0/153 (0.00%)	1/308 (0.32%)
Hepatobiliary disorders
Cholecystitis † 1	0/153 (0.00%)	1/308 (0.32%)
Cholecystitis acute † 1	1/153 (0.65%)	1/308 (0.32%)
Hepatic function abnormal † 1	0/153 (0.00%)	2/308 (0.65%)
Hepatitis toxic † 1	0/153 (0.00%)	1/308 (0.32%)
Venoocclusive liver disease † 1	1/153 (0.65%)	0/308 (0.00%)
Infections and infestations
Acinetobacter infection † 1	0/153 (0.00%)	1/308 (0.32%)
Arthritis bacterial † 1	1/153 (0.65%)	0/308 (0.00%)
Bacteraemia † 1	0/153 (0.00%)	2/308 (0.65%)
Bronchitis † 1	0/153 (0.00%)	6/308 (1.95%)
Campylobacter infection † 1	1/153 (0.65%)	0/308 (0.00%)
Catheter site abscess † 1	0/153 (0.00%)	1/308 (0.32%)
Cellulitis † 1	1/153 (0.65%)	2/308 (0.65%)
Chronic sinusitis † 1	0/153 (0.00%)	1/308 (0.32%)
Clostridium difficile infection † 1	1/153 (0.65%)	0/308 (0.00%)
Device related infection † 1	1/153 (0.65%)	2/308 (0.65%)
Diarrhoea infectious † 1	0/153 (0.00%)	1/308 (0.32%)
Enterocolitis infectious † 1	0/153 (0.00%)	1/308 (0.32%)
Erysipelas † 1	0/153 (0.00%)	1/308 (0.32%)
Gastroenteritis † 1	2/153 (1.31%)	1/308 (0.32%)
Gastroenteritis salmonella † 1	0/153 (0.00%)	1/308 (0.32%)
Herpes zoster † 1	0/153 (0.00%)	1/308 (0.32%)
Infection † 1	1/153 (0.65%)	2/308 (0.65%)
Influenza † 1	3/153 (1.96%)	14/308 (4.55%)
Lower respiratory tract infection † 1	1/153 (0.65%)	7/308 (2.27%)
Meningitis pneumococcal † 1	1/153 (0.65%)	0/308 (0.00%)
Nasopharyngitis † 1	0/153 (0.00%)	1/308 (0.32%)
Otitis media acute † 1	0/153 (0.00%)	1/308 (0.32%)
Peritonitis † 1	1/153 (0.65%)	0/308 (0.00%)
Picornavirus infection † 1	1/153 (0.65%)	0/308 (0.00%)
Pneumococcal sepsis † 1	0/153 (0.00%)	1/308 (0.32%)
Pneumocystis jirovecii pneumonia † 1	0/153 (0.00%)	1/308 (0.32%)
Pneumonia † 1	16/153 (10.46%)	52/308 (16.88%)
Pneumonia bacterial † 1	0/153 (0.00%)	1/308 (0.32%)
Pneumonia cytomegaloviral † 1	0/153 (0.00%)	2/308 (0.65%)
Pneumonia mycoplasmal † 1	0/153 (0.00%)	1/308 (0.32%)
Pneumonia respiratory syncytial viral † 1	0/153 (0.00%)	2/308 (0.65%)
Pneumonia viral † 1	2/153 (1.31%)	0/308 (0.00%)
Respiratory syncytial virus infection † 1	0/153 (0.00%)	3/308 (0.97%)
Respiratory tract infection † 1	2/153 (1.31%)	8/308 (2.60%)
Respiratory tract infection viral † 1	1/153 (0.65%)	0/308 (0.00%)
Rhinovirus infection † 1	1/153 (0.65%)	1/308 (0.32%)
Sepsis † 1	2/153 (1.31%)	12/308 (3.90%)
Septic shock † 1	2/153 (1.31%)	5/308 (1.62%)
Sinusitis † 1	0/153 (0.00%)	1/308 (0.32%)
Skin infection † 1	0/153 (0.00%)	1/308 (0.32%)
Staphylococcal infection † 1	0/153 (0.00%)	1/308 (0.32%)
Streptococcal bacteraemia † 1	0/153 (0.00%)	1/308 (0.32%)
Streptococcal sepsis † 1	0/153 (0.00%)	1/308 (0.32%)
Thrombophlebitis septic † 1	0/153 (0.00%)	1/308 (0.32%)
Upper respiratory tract infection † 1	1/153 (0.65%)	6/308 (1.95%)
Urinary tract infection † 1	3/153 (1.96%)	6/308 (1.95%)
Vascular device infection † 1	1/153 (0.65%)	1/308 (0.32%)
Viral infection † 1	0/153 (0.00%)	2/308 (0.65%)
Appendicitis † 1	0/153 (0.00%)	1/308 (0.32%)
Asymptomatic COVID-19 † 1	0/153 (0.00%)	1/308 (0.32%)
Bronchopulmonary aspergillosis † 1	0/153 (0.00%)	1/308 (0.32%)
COVID-19 † 1	0/153 (0.00%)	3/308 (0.97%)
COVID-19 pneumonia † 1	3/153 (1.96%)	14/308 (4.55%)
Device related bacteraemia † 1	0/153 (0.00%)	1/308 (0.32%)
Endophthalmitis † 1	0/153 (0.00%)	1/308 (0.32%)
Folliculitis † 1	1/153 (0.65%)	0/308 (0.00%)
Herpes dermatitis † 1	0/153 (0.00%)	1/308 (0.32%)
Klebsiella bacteraemia † 1	0/153 (0.00%)	1/308 (0.32%)
Klebsiella infection † 1	0/153 (0.00%)	1/308 (0.32%)
Staphylococcal bacteraemia † 1	0/153 (0.00%)	1/308 (0.32%)
Upper respiratory tract infection bacterial † 1	0/153 (0.00%)	1/308 (0.32%)
Injury, poisoning and procedural complications
Fall † 1	0/153 (0.00%)	1/308 (0.32%)
Femoral neck fracture † 1	1/153 (0.65%)	0/308 (0.00%)
Femur fracture † 1	0/153 (0.00%)	1/308 (0.32%)
Hip fracture † 1	1/153 (0.65%)	0/308 (0.00%)
Infusion related reaction † 1	0/153 (0.00%)	3/308 (0.97%)
Lower limb fracture † 1	0/153 (0.00%)	1/308 (0.32%)
Overdose † 1	0/153 (0.00%)	2/308 (0.65%)
Rib fracture † 1	0/153 (0.00%)	1/308 (0.32%)
Spinal compression fracture † 1	0/153 (0.00%)	1/308 (0.32%)
Spinal fracture † 1	0/153 (0.00%)	1/308 (0.32%)
Sternal fracture † 1	0/153 (0.00%)	1/308 (0.32%)
Thoracic vertebral fracture † 1	2/153 (1.31%)	0/308 (0.00%)
Tracheal obstruction † 1	0/153 (0.00%)	1/308 (0.32%)
Traumatic fracture † 1	0/153 (0.00%)	1/308 (0.32%)
Venous injury † 1	2/153 (1.31%)	0/308 (0.00%)
Dural tear † 1	0/153 (0.00%)	1/308 (0.32%)
Fibula fracture † 1	1/153 (0.65%)	0/308 (0.00%)
Ligament rupture † 1	0/153 (0.00%)	1/308 (0.32%)
Lumbar vertebral fracture † 1	0/153 (0.00%)	1/308 (0.32%)
Patella fracture † 1	0/153 (0.00%)	1/308 (0.32%)
Pelvic fracture † 1	0/153 (0.00%)	1/308 (0.32%)
Investigations
Alanine aminotransferase increased † 1	0/153 (0.00%)	1/308 (0.32%)
Blood creatinine increased † 1	0/153 (0.00%)	2/308 (0.65%)
C-reactive protein increased † 1	0/153 (0.00%)	1/308 (0.32%)
Ejection fraction decreased † 1	0/153 (0.00%)	1/308 (0.32%)
Haemoglobin abnormal † 1	0/153 (0.00%)	1/308 (0.32%)
Liver function test increased † 1	0/153 (0.00%)	1/308 (0.32%)
Medical observation † 1	1/153 (0.65%)	0/308 (0.00%)
Weight decreased † 1	0/153 (0.00%)	1/308 (0.32%)
Metabolism and nutrition disorders
Dehydration † 1	0/153 (0.00%)	1/308 (0.32%)
Hyperglycaemia † 1	0/153 (0.00%)	3/308 (0.97%)
Hyperkalaemia † 1	0/153 (0.00%)	2/308 (0.65%)
Hypoglycaemia † 1	0/153 (0.00%)	1/308 (0.32%)
Hypokalaemia † 1	0/153 (0.00%)	2/308 (0.65%)
Hyponatraemia † 1	0/153 (0.00%)	1/308 (0.32%)
Tumour lysis syndrome † 1	1/153 (0.65%)	2/308 (0.65%)
Hypervolaemia † 1	1/153 (0.65%)	0/308 (0.00%)
Hypocalcaemia † 1	0/153 (0.00%)	1/308 (0.32%)
Steroid diabetes † 1	0/153 (0.00%)	1/308 (0.32%)
Musculoskeletal and connective tissue disorders
Back pain † 1	1/153 (0.65%)	3/308 (0.97%)
Intervertebral disc protrusion † 1	0/153 (0.00%)	1/308 (0.32%)
Osteolysis † 1	0/153 (0.00%)	1/308 (0.32%)
Osteonecrosis of jaw † 1	0/153 (0.00%)	3/308 (0.97%)
Pain in extremity † 1	1/153 (0.65%)	0/308 (0.00%)
Pathological fracture † 1	0/153 (0.00%)	3/308 (0.97%)
Spinal disorder † 1	0/153 (0.00%)	1/308 (0.32%)
Spinal pain † 1	1/153 (0.65%)	0/308 (0.00%)
Myalgia † 1	0/153 (0.00%)	1/308 (0.32%)
Spinal osteoarthritis † 1	0/153 (0.00%)	1/308 (0.32%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	0/153 (0.00%)	1/308 (0.32%)
Plasma cell myeloma † 1	5/153 (3.27%)	8/308 (2.60%)
Plasmacytoma † 1	0/153 (0.00%)	2/308 (0.65%)
Squamous cell carcinoma † 1	0/153 (0.00%)	2/308 (0.65%)
Tumour pain † 1	0/153 (0.00%)	1/308 (0.32%)
Metastases to liver † 1	0/153 (0.00%)	1/308 (0.32%)
Prostate cancer † 1	1/153 (0.65%)	0/308 (0.00%)
Nervous system disorders
Cerebral haemorrhage † 1	0/153 (0.00%)	1/308 (0.32%)
Cerebrovascular accident † 1	0/153 (0.00%)	2/308 (0.65%)
Ischaemic stroke † 1	0/153 (0.00%)	1/308 (0.32%)
Monoparesis † 1	1/153 (0.65%)	1/308 (0.32%)
Optic neuritis † 1	1/153 (0.65%)	0/308 (0.00%)
Posterior reversible encephalopathy syndrome † 1	0/153 (0.00%)	2/308 (0.65%)
Spinal cord compression † 1	1/153 (0.65%)	0/308 (0.00%)
Stupor † 1	0/153 (0.00%)	1/308 (0.32%)
Syncope † 1	0/153 (0.00%)	3/308 (0.97%)
Haemorrhagic stroke † 1	0/153 (0.00%)	1/308 (0.32%)
Intensive care unit acquired weakness † 1	0/153 (0.00%)	1/308 (0.32%)
Loss of consciousness † 1	0/153 (0.00%)	1/308 (0.32%)
Transient ischaemic attack † 1	1/153 (0.65%)	0/308 (0.00%)
Product Issues
Device dislocation † 1	0/153 (0.00%)	1/308 (0.32%)
Device occlusion † 1	0/153 (0.00%)	1/308 (0.32%)
Psychiatric disorders
Agitation † 1	0/153 (0.00%)	1/308 (0.32%)
Anxiety † 1	1/153 (0.65%)	0/308 (0.00%)
Hypomania † 1	0/153 (0.00%)	1/308 (0.32%)
Suicide attempt † 1	1/153 (0.65%)	0/308 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	7/153 (4.58%)	10/308 (3.25%)
Chronic kidney disease † 1	1/153 (0.65%)	1/308 (0.32%)
Renal failure † 1	2/153 (1.31%)	0/308 (0.00%)
Renal impairment † 1	1/153 (0.65%)	0/308 (0.00%)
Calculus urinary † 1	1/153 (0.65%)	0/308 (0.00%)
Hypotonic urinary bladder † 1	0/153 (0.00%)	1/308 (0.32%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/153 (0.65%)	0/308 (0.00%)
Bronchial hyperreactivity † 1	0/153 (0.00%)	1/308 (0.32%)
Bronchopneumopathy † 1	1/153 (0.65%)	0/308 (0.00%)
Chronic obstructive pulmonary disease † 1	0/153 (0.00%)	1/308 (0.32%)
Cough † 1	0/153 (0.00%)	1/308 (0.32%)
Dyspnoea † 1	5/153 (3.27%)	7/308 (2.27%)
Epistaxis † 1	0/153 (0.00%)	1/308 (0.32%)
Interstitial lung disease † 1	0/153 (0.00%)	4/308 (1.30%)
Organising pneumonia † 1	0/153 (0.00%)	1/308 (0.32%)
Pleural effusion † 1	1/153 (0.65%)	3/308 (0.97%)
Pneumonitis † 1	0/153 (0.00%)	2/308 (0.65%)
Pulmonary arterial hypertension † 1	0/153 (0.00%)	2/308 (0.65%)
Pulmonary embolism † 1	5/153 (3.27%)	7/308 (2.27%)
Pulmonary hypertension † 1	1/153 (0.65%)	2/308 (0.65%)
Pulmonary oedema † 1	2/153 (1.31%)	5/308 (1.62%)
Pulmonary toxicity † 1	1/153 (0.65%)	0/308 (0.00%)
Respiratory failure † 1	0/153 (0.00%)	3/308 (0.97%)
Hiccups † 1	0/153 (0.00%)	1/308 (0.32%)
Skin and subcutaneous tissue disorders
Rash † 1	1/153 (0.65%)	0/308 (0.00%)
Rash maculo-papular † 1	1/153 (0.65%)	0/308 (0.00%)
Surgical and medical procedures
Arteriovenous fistula operation † 1	0/153 (0.00%)	1/308 (0.32%)
Vascular disorders
Aortic stenosis † 1	0/153 (0.00%)	1/308 (0.32%)
Deep vein thrombosis † 1	2/153 (1.31%)	1/308 (0.32%)
Hypertension † 1	3/153 (1.96%)	3/308 (0.97%)
Hypertensive crisis † 1	1/153 (0.65%)	0/308 (0.00%)
Poor venous access † 1	1/153 (0.65%)	0/308 (0.00%)
Venous thrombosis † 1	0/153 (0.00%)	1/308 (0.32%)
Dialysis hypotension † 1	1/153 (0.65%)	0/308 (0.00%)
Hypertensive urgency † 1	0/153 (0.00%)	1/308 (0.32%)
1 Term from vocabulary, MedDRA 25.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Kd - Carfilzomib and Dexamethasone	KdD - Carfilzomib, Dexamethasone and Daratumumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	137/153 (89.54%)	295/308 (95.78%)
Blood and lymphatic system disorders
Anaemia † 1	51/153 (33.33%)	113/308 (36.69%)
Leukopenia † 1	6/153 (3.92%)	21/308 (6.82%)
Lymphopenia † 1	13/153 (8.50%)	29/308 (9.42%)
Neutropenia † 1	15/153 (9.80%)	49/308 (15.91%)
Thrombocytopenia † 1	46/153 (30.07%)	119/308 (38.64%)
Cardiac disorders
Tachycardia † 1	8/153 (5.23%)	12/308 (3.90%)
Eye disorders
Cataract † 1	11/153 (7.19%)	28/308 (9.09%)
Gastrointestinal disorders
Constipation † 1	7/153 (4.58%)	23/308 (7.47%)
Diarrhoea † 1	27/153 (17.65%)	112/308 (36.36%)
Nausea † 1	22/153 (14.38%)	62/308 (20.13%)
Vomiting † 1	13/153 (8.50%)	52/308 (16.88%)
Abdominal pain † 1	9/153 (5.88%)	13/308 (4.22%)
General disorders
Asthenia † 1	19/153 (12.42%)	35/308 (11.36%)
Chills † 1	7/153 (4.58%)	18/308 (5.84%)
Fatigue † 1	29/153 (18.95%)	80/308 (25.97%)
Oedema † 1	8/153 (5.23%)	14/308 (4.55%)
Oedema peripheral † 1	16/153 (10.46%)	38/308 (12.34%)
Pyrexia † 1	24/153 (15.69%)	57/308 (18.51%)
Immune system disorders
Hypogammaglobulinaemia † 1	4/153 (2.61%)	17/308 (5.52%)
Infections and infestations
Bronchitis † 1	21/153 (13.73%)	56/308 (18.18%)
Conjunctivitis † 1	5/153 (3.27%)	16/308 (5.19%)
Influenza † 1	10/153 (6.54%)	26/308 (8.44%)
Nasopharyngitis † 1	15/153 (9.80%)	33/308 (10.71%)
Pneumonia † 1	9/153 (5.88%)	38/308 (12.34%)
Respiratory tract infection † 1	9/153 (5.88%)	33/308 (10.71%)
Upper respiratory tract infection † 1	37/153 (24.18%)	104/308 (33.77%)
Urinary tract infection † 1	3/153 (1.96%)	22/308 (7.14%)
COVID-19 † 1	3/153 (1.96%)	16/308 (5.19%)
Lower respiratory tract infection † 1	4/153 (2.61%)	20/308 (6.49%)
Pharyngitis † 1	4/153 (2.61%)	18/308 (5.84%)
Sinusitis † 1	5/153 (3.27%)	16/308 (5.19%)
Injury, poisoning and procedural complications
Infusion related reaction † 1	3/153 (1.96%)	23/308 (7.47%)
Contusion † 1	2/153 (1.31%)	16/308 (5.19%)
Fall † 1	6/153 (3.92%)	17/308 (5.52%)
Metabolism and nutrition disorders
Decreased appetite † 1	9/153 (5.88%)	27/308 (8.77%)
Hyperglycaemia † 1	13/153 (8.50%)	29/308 (9.42%)
Hypokalaemia † 1	12/153 (7.84%)	23/308 (7.47%)
Hypocalcaemia † 1	7/153 (4.58%)	19/308 (6.17%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	11/153 (7.19%)	35/308 (11.36%)
Back pain † 1	20/153 (13.07%)	61/308 (19.81%)
Muscle spasms † 1	19/153 (12.42%)	41/308 (13.31%)
Pain in extremity † 1	11/153 (7.19%)	25/308 (8.12%)
Muscular weakness † 1	6/153 (3.92%)	21/308 (6.82%)
Musculoskeletal chest pain † 1	6/153 (3.92%)	18/308 (5.84%)
Myalgia † 1	4/153 (2.61%)	18/308 (5.84%)
Nervous system disorders
Dizziness † 1	7/153 (4.58%)	24/308 (7.79%)
Headache † 1	19/153 (12.42%)	47/308 (15.26%)
Neuropathy peripheral † 1	6/153 (3.92%)	34/308 (11.04%)
Peripheral sensory neuropathy † 1	2/153 (1.31%)	26/308 (8.44%)
Psychiatric disorders
Insomnia † 1	19/153 (12.42%)	64/308 (20.78%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	30/153 (19.61%)	55/308 (17.86%)
Dyspnoea † 1	34/153 (22.22%)	68/308 (22.08%)
Productive cough † 1	6/153 (3.92%)	21/308 (6.82%)
Epistaxis † 1	8/153 (5.23%)	9/308 (2.92%)
Oropharyngeal pain † 1	4/153 (2.61%)	16/308 (5.19%)
Skin and subcutaneous tissue disorders
Rash † 1	10/153 (6.54%)	21/308 (6.82%)
Pruritus † 1	5/153 (3.27%)	19/308 (6.17%)
Vascular disorders
Hypertension † 1	47/153 (30.72%)	113/308 (36.69%)
1 Term from vocabulary, MedDRA 25.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.

Results Point of Contact

• Name/Title: Study Director
• Organization: Amgen Inc.
• Phone: 866-572-6436
• EMail: medinfo@amgen.com

Publications:

Quach H, Nooka A, Samoylova O, Venner CP, Kim K, Facon T, Spencer A, Usmani SZ, Grosicki S, Suzuki K, Delimpasi S, Weisel K, Obreja M, Zahlten-Kumeli A, Mateos MV. Carfilzomib, dexamethasone and daratumumab in relapsed or refractory multiple myeloma: results of the phase III study CANDOR by prior lines of therapy. Br J Haematol. 2021 Aug;194(4):784-788. doi: 10.1111/bjh.17541. Epub 2021 May 28. No abstract available.

Siegel D, Weisel K, Zahlten-Kumeli A, Medhekar R, Ding B, Leleu X. Health-related quality of life outcomes from the CANDOR study in patients with relapsed or refractory multiple myeloma. Leuk Lymphoma. 2021 Dec;62(12):3002-3010. doi: 10.1080/10428194.2021.1941927. Epub 2021 Jun 26.

Suzuki K, Min CK, Kim K, Lee JJ, Shibayama H, Ko PS, Huang SY, Li SS, Ding B, Khurana M, Iida S. Carfilzomib, dexamethasone, and daratumumab in Asian patients with relapsed or refractory multiple myeloma: post hoc subgroup analysis of the phase 3 CANDOR trial. Int J Hematol. 2021 Dec;114(6):653-663. doi: 10.1007/s12185-021-03204-9. Epub 2021 Aug 19.

Usmani SZ, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Gavriatopoulou M, Oriol A, Rabin N, Nooka A, Qi M, Beksac M, Jakubowiak A, Ding B, Zahlten-Kumeli A, Yusuf A, Dimopoulos M. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Lancet Oncol. 2022 Jan;23(1):65-76. doi: 10.1016/S1470-2045(21)00579-9. Epub 2021 Dec 3.

Landgren O, Weisel K, Rosinol L, Touzeau C, Turgut M, Hajek R, Mollee P, Kim JS, Shu N, Hu X, Li C, Usmani SZ. Subgroup analysis based on cytogenetic risk in patients with relapsed or refractory multiple myeloma in the CANDOR study. Br J Haematol. 2022 Sep;198(6):988-993. doi: 10.1111/bjh.18233. Epub 2022 May 24.

Dimopoulos M, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Yang H, Klippel Z, Zahlten-Kumeli A, Usmani SZ. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020 Jul 18;396(10245):186-197. doi: 10.1016/S0140-6736(20)30734-0. Erratum In: Lancet. 2020 Aug 15;396(10249):466.

Leleu X, Beksac M, Chou T, Dimopoulos M, Yoon SS, Prince HM, Pour L, Shelekhova T, Chari A, Khurana M, Zhang J, Obreja M, Qi M, Oriol A, Siegel D. Efficacy and safety of weekly carfilzomib (70 mg/m2), dexamethasone, and daratumumab (KdD70) is comparable to twice-weekly KdD56 while being a more convenient dosing option: a cross-study comparison of the CANDOR and EQUULEUS studies. Leuk Lymphoma. 2021 Feb;62(2):358-367. doi: 10.1080/10428194.2020.1832672. Epub 2020 Oct 28.

Usmani SZ, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, Weisel K, Shu X, Li C, Dimopoulos M. Final analysis of carfilzomib, dexamethasone, and daratumumab vs carfilzomib and dexamethasone in the CANDOR study. Blood Adv. 2023 Jul 25;7(14):3739-3748. doi: 10.1182/bloodadvances.2023010026.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT03158688
• Other Study ID Numbers: 20160275; 2016-003554-33 ( EudraCT Number )
• First Submitted: May 9, 2017
• First Posted: May 18, 2017
• Results First Submitted: July 13, 2020
• Results First Posted: September 11, 2020
• Last Update Posted: March 5, 2024