Daratumumab Retreatment in Participants With Multiple Mye... | NCT03871829

NCT03871829

ID	Type	Description	Link
2018-004185-34	EudraCT Number
54767414MMY2065	Other Identifier	Janssen Research & Development, LLC

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A: Carfilzomib+Dexamethasone (Kd)	Active Comparator	Participants will receive carfilzomib 20 milligram per square meter (mg/m^2) intravenously (IV) on Day 1 of Cycle 1 and then 70 mg/m^2 on Days 8 and 15 of Cycle 1 and thereafter on Days 1, 8, 15 of Cycle 2 onwards. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days.	Drug: Carfilzomib 20 mg/m^2 Drug: Carfilzomib 70 mg/m^2 Drug: Dexamethasone 40 mg Drug: Dexamethasone 20 mg
Arm B: Dara-SC in combination with Kd (DKd)	Experimental	Participants will receive daratumumab subcutaneous (Dara-SC) 1800 mg by SC injection on Days 1, 8, 15, 22 for Cycle 1 and 2, Days 1 and 15 for Cycle 3-6, Day 1 for Cycle 7 onwards. Participants will receive carfilzomib 20 mg/m^2 IV on Cycle 1 Day 1 and then 70 mg/m^2 on Day 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days.	Drug: Carfilzomib 20 mg/m^2 Drug: Carfilzomib 70 mg/m^2 Drug: Dexamethasone 40 mg Drug: Dara-SC 1800 mg Drug: Dexamethasone 20 mg

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Carfilzomib 20 mg/m^2	Drug	Carfilzomib 20 mg/m^2 will be administered intravenously (IV).	Arm A: Carfilzomib+Dexamethasone (Kd) Arm B: Dara-SC in combination with Kd (DKd)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response	Percentage of participants achieving VGPR or better response were reported. VGPR or better rate was defined as the percentage of participants achieving VGPR, complete response (CR), or stringent complete response (sCR) in accordance with the International Myeloma Working Group (IMWG) criteria, during or after the study treatment but before the start of subsequent anti-myeloma therapy. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than or equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein less than (<) 100 milligram (mg)/24 hours; for CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and <5% PCs in bone marrow; for sCR: CR plus normal free light chain (FLC) ratio, and Absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4- color flow cytometry.	Up to 3 years and 4 months

Secondary Outcomes

Measure	Description	Time Frame
Overall Response Rate (ORR)	ORR was defined as the percentage of participants who achieved partial response (PR) or better responses based on the computerized algorithm, in accordance with the IMWG criteria, during or after the study treatment but before the start of subsequent anti-myeloma therapy. IMWG criteria for PR: greater than or equal to (>=)50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or less than (<)200 mg/24 hours; If the serum and urine M-protein were not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels was required in place of the M-protein criteria; If serum and urine M-protein were not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) was required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%; additionally, if present at baseline, >=50% reduction in the size of soft tissue PCs was also required.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Evidence of a response (partial response or better based on investigator's determination of response by International Myeloma Working Group [IMWG] criteria) to daratumumab-containing therapy with response duration of at least 4 months
Participants must have progressed from or be refractory to their last line of treatment. Relapsed or refractory disease as defined as: a) Relapsed disease is defined as an initial response to previous treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or >60 days after cessation of treatment
Received 1 to 3 prior line(s) of treatment of which one contained daratumumab, and completed daratumumab at least 3 months prior to randomization. A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram per day [mg/day] for 4 days) would not be considered prior lines of therapy
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization

Exclusion Criteria:

Previous treatment with daratumumab within the last 3 months prior to randomization
Discontinuation of daratumumab due to a daratumumab-related adverse event (AE)
History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
Allergies, hypersensitivity, or intolerance to daratumumab, hyaluronidase, monoclonal antibodies (mAbs), human proteins, or their excipients, or known sensitivity to mammalian-derived products. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
Participant is: a) Known to be seropositive for human immunodeficiency virus (HIV) with one or more of the following: not receiving highly active antiretroviral therapy (ART), had a change in ART within 6 months of the start of screening, receiving ART that may interfere with study treatment, cluster of differentiation (CD)4 count <350 (unit: cells per cubic millimeter of blood) at screening, acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of start of screening, and not agreeing to start ART and be on ART >4 weeks plus having HIV viral load <400 copies/milliliters (mL) at end of 4-week period (to ensure ART is tolerated and HIV controlled. b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (example: participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. c) Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)

Name	Affiliation	Role
Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Banner MD Anderson Cancer Center		Gilbert	Arizona	85234	United States
Oncology Institute of Hope and Innovation

PubMed Identifier	Type	Citation	Retractions
41041907	Derived	Bahlis NJ, Zonder J, Karlin L, Plesner T, Paris L, Wrobel T, Hungria V, Besemer B, Crusoe E, Silkjaer T, Perrot A, Moreau P, Wu KL, Delimpasi S, Dimopoulos MA, Levin MD, Mangiacavalli S, Nnane I, Kim YJ, Krevvata M, Sha L, Wroblewski S, Tuozzo A, Carson R, Facon T. Subcutaneous daratumumab plus carfilzomib and dexamethasone (D-Kd) versus carfilzomib and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma who received previous daratumumab treatment: LYNX study. Leuk Lymphoma. 2025 Dec;66(14):2685-2696. doi: 10.1080/10428194.2025.2561117. Epub 2025 Oct 3.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A: Carfilzomib+Dexamethasone (Kd)	Participants received carfilzomib 20 milligram per meter square (mg/m^2) intravenously (IV) on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and thereafter on Days 1, 8, 15 from Cycle 2 onwards. Participants received dexamethasone 20 milligrams (mg) on Cycle 1 Days 1 and 2, and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed progressive disease (PD), death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 3, 2021	Oct 12, 2023

Arm/Group Information

ID	Title	Description
BG000	Arm A: Carfilzomib+Dexamethasone (Kd)	Participants received carfilzomib 20 milligram per meter square (mg/m^2) intravenously (IV) on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and thereafter on Days 1, 8, 15 from Cycle 2 onwards. Participants received dexamethasone 20 milligrams (mg) on Cycle 1 Days 1 and 2, and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed progressive disease (PD), death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.
BG001	Arm B: Dara-SC in Combination With Kd (DKd)	Participants received daratumumab 1800 mg by SC injection (Dara-SC) on Days 1, 8, 15, 22 of Cycle 1 and 2, Days 1 and 15 of Cycle 3-6, and on Day 1 from Cycle 7 onwards. Participants received carfilzomib 20 mg/m^2 IV on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and Days 1, 8 and 15 from Cycle 2 onwards. Participants received dexamethasone 20 mg on Cycle 1 Days 1 and 2 and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed PD, death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00046.2± 32.3(32.3 to 60.4) OG00148.8± 35.1(35.1 to 62.6)

Secondary

Overall Response Rate (ORR)

ORR was defined as the percentage of participants who achieved partial response (PR) or better responses based on the computerized algorithm, in accordance with the IMWG criteria, during or after the study treatment but before the start of subsequent anti-myeloma therapy. IMWG criteria for PR: greater than or equal to (>=)50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or less than (<)200 mg/24 hours; If the serum and urine M-protein were not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels was required in place of the M-protein criteria; If serum and urine M-protein were not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) was required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%; additionally, if present at baseline, >=50% reduction in the size of soft tissue PCs was also required.

The response-evaluable analysis set included participants who had confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit.

Posted

Number

90% Confidence Interval

Percentage of participants

Up to 3 years and 7 months

ID	Title	Description
OG000	Arm A: Carfilzomib+Dexamethasone (Kd)	Participants received carfilzomib 20 milligram per meter square (mg/m^2) intravenously (IV) on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and thereafter on Days 1, 8, 15 from Cycle 2 onwards. Participants received dexamethasone 20 milligrams (mg) on Cycle 1 Days 1 and 2, and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed progressive disease (PD), death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.

Secondary

Percentage of Participants Achieving Complete Response (CR) or Better

Percentage of participants achieving CR or better were reported. CR or better rate was defined as the percentage of participants achieving CR or sCR based on the computerized algorithm, according to IMWG response criteria. IMWG criteria for CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and <5% PCs in bone marrow.

The response-evaluable analysis set included participants who had confirmed diagnosis of multiple myeloma and measurable disease at baseline or screening visit.

Posted

Number

90% Confidence Interval

Percentage of participants

Up to 3 years and 7 months

ID	Title	Description
OG000	Arm A: Carfilzomib+Dexamethasone (Kd)	Participants received carfilzomib 20 milligram per meter square (mg/m^2) intravenously (IV) on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and thereafter on Days 1, 8, 15 from Cycle 2 onwards. Participants received dexamethasone 20 milligrams (mg) on Cycle 1 Days 1 and 2, and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed progressive disease (PD), death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.
OG001	Arm B: Dara-SC in Combination With Kd (DKd)

Secondary

Progression Free Survival (PFS)

PFS was defined as the duration from the date of randomization to either progressive disease (PD) or death, whichever comes first. IMWG criteria for PD: >=25% from lowest response level in serum M-component (the absolute increase must be >=0.5 gram per deciliter [g/dL]) and/or in urine M-component (the absolute increase must be >=200 mg/24 hour); only in participants without measurable serum and urine M-protein levels: increase of >=25% in the difference between involved and uninvolved free light chain levels and the absolute increase must be >10 mg/dL. BMPC%: the absolute % must be >=10%; definite increase in size of existing bone lesions or soft tissue plasmacytomas; definite development of new bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 milligrams per deciliter (mg/dL) or 2.65 millimoles per liter [mmol/L]) that can be attributed solely to PC proliferative disorder.

Intent-to-treat (ITT) analysis set included all participants who were randomized in the study. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.

Posted

Median

90% Confidence Interval

months

Up to 3 years and 7 months

ID	Title	Description
OG000	Arm A: Carfilzomib+Dexamethasone (Kd)	Participants received carfilzomib 20 milligram per meter square (mg/m^2) intravenously (IV) on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and thereafter on Days 1, 8, 15 from Cycle 2 onwards. Participants received dexamethasone 20 milligrams (mg) on Cycle 1 Days 1 and 2, and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed progressive disease (PD), death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.

Secondary

Overall Survival (OS)

OS was defined as the time from the date of randomization to the date of the participant's death due to any cause.

ITT analysis set included all participants who were randomized in the study. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.

Posted

Median

90% Confidence Interval

months

Up to 3 years and 7 months

ID	Title	Description
OG000	Arm A: Carfilzomib+Dexamethasone (Kd)	Participants received carfilzomib 20 milligram per meter square (mg/m^2) intravenously (IV) on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and thereafter on Days 1, 8, 15 from Cycle 2 onwards. Participants received dexamethasone 20 milligrams (mg) on Cycle 1 Days 1 and 2, and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed progressive disease (PD), death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.
OG001	Arm B: Dara-SC in Combination With Kd (DKd)	Participants received daratumumab 1800 mg by SC injection (Dara-SC) on Days 1, 8, 15, 22 of Cycle 1 and 2, Days 1 and 15 of Cycle 3-6, and on Day 1 from Cycle 7 onwards. Participants received carfilzomib 20 mg/m^2 IV on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and Days 1, 8 and 15 from Cycle 2 onwards. Participants received dexamethasone 20 mg on Cycle 1 Days 1 and 2 and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed PD, death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.

Secondary

Percentage of Participants With Negative Minimal Residual Disease (MRD)

Percentage of participants with negative MRD were reported. MRD negativity rate, defined as the percentage of participants who had MRD negative status at 10^-5 by bone marrow aspirate after the date of randomization and prior to PD or subsequent anti-myeloma therapy.

ITT analysis set included all participants who were randomized in the study.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 3 years and 7 months

ID	Title	Description
OG000	Arm A: Carfilzomib+Dexamethasone (Kd)	Participants received carfilzomib 20 milligram per meter square (mg/m^2) intravenously (IV) on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and thereafter on Days 1, 8, 15 from Cycle 2 onwards. Participants received dexamethasone 20 milligrams (mg) on Cycle 1 Days 1 and 2, and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed progressive disease (PD), death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.
OG001	Arm B: Dara-SC in Combination With Kd (DKd)	Participants received daratumumab 1800 mg by SC injection (Dara-SC) on Days 1, 8, 15, 22 of Cycle 1 and 2, Days 1 and 15 of Cycle 3-6, and on Day 1 from Cycle 7 onwards. Participants received carfilzomib 20 mg/m^2 IV on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and Days 1, 8 and 15 from Cycle 2 onwards. Participants received dexamethasone 20 mg on Cycle 1 Days 1 and 2 and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed PD, death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.

Secondary

Time to Next Treatment

Time to next treatment was defined as the time from randomization to the start of the next-line treatment.

ITT analysis set analysis set included all participants who were randomized in the study. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.

Posted

Median

90% Confidence Interval

months

Up to 3 years and 7 months

ID	Title	Description
OG000	Arm A: Carfilzomib+Dexamethasone (Kd)	Participants received carfilzomib 20 milligram per meter square (mg/m^2) intravenously (IV) on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and thereafter on Days 1, 8, 15 from Cycle 2 onwards. Participants received dexamethasone 20 milligrams (mg) on Cycle 1 Days 1 and 2, and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed progressive disease (PD), death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.
OG001	Arm B: Dara-SC in Combination With Kd (DKd)	Participants received daratumumab 1800 mg by SC injection (Dara-SC) on Days 1, 8, 15, 22 of Cycle 1 and 2, Days 1 and 15 of Cycle 3-6, and on Day 1 from Cycle 7 onwards. Participants received carfilzomib 20 mg/m^2 IV on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and Days 1, 8 and 15 from Cycle 2 onwards. Participants received dexamethasone 20 mg on Cycle 1 Days 1 and 2 and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed PD, death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.

Secondary

Serum Concentrations of Daratumumab

Serum concentrations of daratumumab were assessed. This outcome measure was planned to be analyzed for specified arm only.

Pharmacokinetic (PK) analysis set included all participants who had received at least 1 dose of daratumumab subcutaneous (dara-SC) and had at least 1 post-dose PK sample. Here, 'N' (number of participants analysed) signifies participants who were evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants analyzed at each specified timepoints.

Posted

Mean

Standard Deviation

microgram per milliliters (mcg/mL)

Day 1 of Cycles 1, 3, and 7 (each cycle of 28 days) and Follow Up (post treatment Week 8; up to 30.3 months)

ID	Title	Description
OG000	Arm B: Dara-SC in Combination With Kd (DKd)	Participants received daratumumab 1800 mg by SC injection (Dara-SC) on Days 1, 8, 15, 22 of Cycle 1 and 2, Days 1 and 15 of Cycle 3-6, and on Day 1 from Cycle 7 onwards. Participants received carfilzomib 20 mg/m^2 IV on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and Days 1, 8 and 15 from Cycle 2 onwards. Participants received dexamethasone 20 mg on Cycle 1 Days 1 and 2 and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed PD, death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.

Secondary

Number of Participants With Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies

The incidence of anti-rHuPH20 antibodies were summarized for all participants who received at least one dose of Dara-SC and had appropriate plasma samples for detection of antibodies to rHuPH20 (at least 1 sample after the start of the first dose of Dara-SC). This outcome measure was planned to be analyzed for specified arm only.

The immunogenicity analysis set for dara-SC included all randomized participants who had appropriate samples for detection of the antibodies.

Posted

Count of Participants

Participants

Up to end of study; up to 30.3 months

ID	Title	Description
OG000	Arm B: Dara-SC in Combination With Kd (DKd)	Participants received daratumumab 1800 mg by SC injection (Dara-SC) on Days 1, 8, 15, 22 of Cycle 1 and 2, Days 1 and 15 of Cycle 3-6, and on Day 1 from Cycle 7 onwards. Participants received carfilzomib 20 mg/m^2 IV on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and Days 1, 8 and 15 from Cycle 2 onwards. Participants received dexamethasone 20 mg on Cycle 1 Days 1 and 2 and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed PD, death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.

Secondary

Number of Participants With Anti-Daratumumab Antibodies

Number of participants who test positive for anti-daratumumab antibodies were reported. This outcome measure was planned to be analyzed for specified arm only.

The immunogenicity analysis set for dara-SC included all randomized participants who had appropriate samples for detection of the antibodies.

Posted

Count of Participants

Participants

Up to end of study; up to 30.3 months

ID	Title	Description
OG000	Arm B: Dara-SC in Combination With Kd (DKd)	Participants received daratumumab 1800 mg by SC injection (Dara-SC) on Days 1, 8, 15, 22 of Cycle 1 and 2, Days 1 and 15 of Cycle 3-6, and on Day 1 from Cycle 7 onwards. Participants received carfilzomib 20 mg/m^2 IV on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and Days 1, 8 and 15 from Cycle 2 onwards. Participants received dexamethasone 20 mg on Cycle 1 Days 1 and 2 and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed PD, death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A: Carfilzomib+Dexamethasone (Kd)	Participants received carfilzomib 20 milligram per meter square (mg/m^2) intravenously (IV) on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and thereafter on Days 1, 8, 15 from Cycle 2 onwards. Participants received dexamethasone 20 milligrams (mg) on Cycle 1 Days 1 and 2, and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed progressive disease (PD), death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.	12	44	20	43	39	43
EG001	Arm B: Dara-SC in Combination With Kd (DKd)	Participants received daratumumab 1800 mg by SC injection (Dara-SC) on Days 1, 8, 15, 22 of Cycle 1 and 2, Days 1 and 15 of Cycle 3-6, and on Day 1 from Cycle 7 onwards. Participants received carfilzomib 20 mg/m^2 IV on Cycle 1 Day 1 and then 70 mg/m^2 on Cycle 1 Days 8 and 15, and Days 1, 8 and 15 from Cycle 2 onwards. Participants received dexamethasone 20 mg on Cycle 1 Days 1 and 2 and 40 mg IV or orally on Days 8, 15, 22 of Cycle 1. Participants then received dexamethasone 40 mg IV or orally on Days 1, 8, 15 and 22 of Cycles 2-9, then on Days 1, 8, 15 from Cycle 10 onwards, until confirmed PD, death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study, whichever occurs first. Each cycle of 28 days.	8	44	12	43	37	43

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected43 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected43 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk
Cardiac failure	Cardiac disorders	MedDRA 24.0	Non-systematic Assessment	EG0003 events2 affected43 at risk EG0010 events0 affected43 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0011 events1 affected43 at risk
Noninfective sialoadenitis	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk
General physical health deterioration	General disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk
Pyrexia	General disorders	MedDRA 24.0	Non-systematic Assessment	EG0004 events2 affected43 at risk EG0010 events0 affected43 at risk
Bacteraemia	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk
COVID-19	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0002 events1 affected43 at risk EG0015 events3 affected43 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0011 events1 affected43 at risk
Escherichia sepsis	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected43 at risk
Infection	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk
Pneumonia	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0004 events4 affected43 at risk EG0012 events2 affected43 at risk
Sinusitis	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected43 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk
Urinary tract infection	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected43 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Non-systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected43 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 24.0	Non-systematic Assessment	EG0005 events4 affected43 at risk EG0010 events0 affected43 at risk
Renal impairment	Renal and urinary disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected43 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected43 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0002 events2 affected43 at risk EG0010 events0 affected43 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0012 events1 affected43 at risk
Hypertension	Vascular disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected43 at risk
Hypotension	Vascular disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected43 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.0	Non-systematic Assessment	EG00037 events14 affected43 at risk EG00120 events11 affected43 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 24.0	Non-systematic Assessment	EG0002 events1 affected43 at risk EG0015 events4 affected43 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 24.0	Non-systematic Assessment	EG00014 events8 affected43 at risk EG00115 events3 affected43 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 24.0	Non-systematic Assessment	EG0006 events4 affected43 at risk EG00118 events8 affected43 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 24.0	Non-systematic Assessment	EG00032 events8 affected43 at risk EG00177 events16 affected43 at risk
Cataract	Eye disorders	MedDRA 24.0	Non-systematic Assessment	EG0002 events2 affected43 at risk EG0013 events3 affected43 at risk
Constipation	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0005 events4 affected43 at risk EG0012 events1 affected43 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG00014 events11 affected43 at risk EG0018 events4 affected43 at risk
Nausea	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0007 events7 affected43 at risk EG00114 events6 affected43 at risk
Vomiting	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0005 events5 affected43 at risk EG0019 events5 affected43 at risk
Asthenia	General disorders	MedDRA 24.0	Non-systematic Assessment	EG0008 events6 affected43 at risk EG0017 events5 affected43 at risk
Catheter site pain	General disorders	MedDRA 24.0	Non-systematic Assessment	EG0003 events3 affected43 at risk EG0010 events0 affected43 at risk
Fatigue	General disorders	MedDRA 24.0	Non-systematic Assessment	EG0004 events3 affected43 at risk EG00111 events7 affected43 at risk
Malaise	General disorders	MedDRA 24.0	Non-systematic Assessment	EG0004 events3 affected43 at risk EG0010 events0 affected43 at risk
Oedema peripheral	General disorders	MedDRA 24.0	Non-systematic Assessment	EG0003 events3 affected43 at risk EG0016 events5 affected43 at risk
Pyrexia	General disorders	MedDRA 24.0	Non-systematic Assessment	EG0004 events4 affected43 at risk EG0019 events5 affected43 at risk
COVID-19	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG00010 events9 affected43 at risk EG0019 events9 affected43 at risk
Nasopharyngitis	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0004 events3 affected43 at risk EG0012 events2 affected43 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG00012 events9 affected43 at risk EG0013 events2 affected43 at risk
Urinary tract infection	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0013 events3 affected43 at risk
Blood creatinine increased	Investigations	MedDRA 24.0	Non-systematic Assessment	EG0002 events2 affected43 at risk EG0017 events4 affected43 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 24.0	Non-systematic Assessment	EG00012 events4 affected43 at risk EG0014 events3 affected43 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0005 events4 affected43 at risk EG0012 events2 affected43 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0006 events4 affected43 at risk EG0015 events4 affected43 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected43 at risk EG0015 events3 affected43 at risk
Headache	Nervous system disorders	MedDRA 24.0	Non-systematic Assessment	EG00012 events7 affected43 at risk EG0012 events2 affected43 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 24.0	Non-systematic Assessment	EG0003 events3 affected43 at risk EG0012 events2 affected43 at risk
Anxiety	Psychiatric disorders	MedDRA 24.0	Non-systematic Assessment	EG0002 events2 affected43 at risk EG0014 events3 affected43 at risk
Insomnia	Psychiatric disorders	MedDRA 24.0	Non-systematic Assessment	EG00011 events6 affected43 at risk EG0012 events2 affected43 at risk
Dysuria	Renal and urinary disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 events0 affected43 at risk EG0015 events3 affected43 at risk
Renal impairment	Renal and urinary disorders	MedDRA 24.0	Non-systematic Assessment	EG0005 events5 affected43 at risk EG0012 events1 affected43 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0005 events5 affected43 at risk EG0017 events6 affected43 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0006 events4 affected43 at risk EG00113 events7 affected43 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0004 events3 affected43 at risk EG0010 events0 affected43 at risk
Hypertension	Vascular disorders	MedDRA 24.0	Non-systematic Assessment	EG00013 events7 affected43 at risk EG00134 events11 affected43 at risk

ID	Term
D054219	Neoplasms, Plasma Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D006474	Hemorrhagic Disorders
D008232	Lymphoproliferative Disorders
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013259	Steroids, Fluorinated