Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab Intravenous (Dara-IV)

For relapsed or refractory multiple myeloma, the treatment is determined on an individual
basis. Common standard of care regimens use either a proteasome inhibitor (PI) or an
immunomodulatory agent (IMiD) in combination with dexamethasone with or without a monoclonal
antibody (mAb) such as daratumumab. After relapse from PIs or IMiDs, patients are often
retreated with drugs that have same mechanism of action to which they have been sensitive.
The disease becomes refractory and all effective treatment options are exhausted. Daratumumab
is a human IgG1 mAb that binds with high affinity to unique epitope on cluster of
differentiation 38 (CD38) and attacks tumor cells that overexpress CD38. Study is to
determine the efficacy of Dara-SC in combination with carfilzomib and dexamethasone (DKd) in
adult participants with relapsed refractory MM who had 1 or 2 prior line(s) of treatment
including a line containing Dara-IV to evaluate daratumumab retreatment. The MM treatment is
determined on an individual basis where patient's age, prior therapy, bone marrow function,
co-morbidities, patient preference and time to relapse are considered. Common standard of
care regimens use either PI or an IMiD in combination with dexamethasone with or without a
mAb. It is a targeted immunotherapy that attacks tumor cells that overexpress CD38, a
transmembrane glycoprotein, in a variety of hematological malignancies including multiple
myeloma. The study will be conducted in 3 phases: Screening (28 days), Treatment, and
Follow-Up. Assessments like chest X-ray, spirometry test, electrocardiogram (ECG), will be
performed during Screening phase. During the Treatment Phase, participants will be randomized
to receive Kd or DKd. Efficacy assessments like bone marrow examination will be performed.
Follow-up will continue until the end of study.

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 intravenously (IV) therapy with response duration of at least 4
months

- 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 or 2 prior line(s) of treatment of which one contained Dara IV, and
completed Dara IV 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 Dara IV 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. 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)