A Study of Daratumumab With the Addition of Recombinant Human Hyaluronidase (rHuPH20) for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma

The purpose of the study is to evaluate the pharmacokinetics and safety from the mixture of daratumumab and rHuPH20 prepared immediately before administration via Subcutaneous (SC) delivery (Part 1) and CF (co-formulated daratumumab and rHuPH20 preparation) administration via SC delivery of daratumumab (Part 2) and to evaluate the safety of Dara-CF 1800 milligram (mg) SC delivery without pre-dose and post-dose corticosteroids (Part 3).

This is an open-label (identity of assigned study drug will be known), multicenter, 3-part, Phase 1b dose escalation/expansion study to evaluate the safety, pharmacokinetics (study of what the body does to a drug), and antitumor activity of SC delivery of daratumumab to participant with relapsed or refractory multiple myeloma. Up to approximately 53 participants in part 1, 80 participants in part 2 and 15 participants per corticosteroid tapering cohort (up to approximately 30 participants total) in Part 3 will be enrolled. The purpose of Part 1 is to select an appropriate SC therapeutic dose for the mixture of daratumumab with rHuPH20 based on safety and pharmacokinetics. This dose, selected from part 1 will be the initial dose for the co-formulated daratumumab and rHuPH20 preparation to be evaluated in Part 2. The purpose of Part 2 is to evaluate the SC delivery of CF and confirm the dose level selected from Part 1 based on the pharmacokinetics, safety, and antitumor activity. The purpose of Part 3 is to evaluate the safety of Dara-CF 1800 mg SC delivery without pre-dose and post-dose corticosteroids. Participant's safety will be monitored throughout the study.

Eligibility Criteria:
Inclusion Criteria:

* Participants proven to have multiple myeloma (MM) diagnosis according to the International Myeloma Working Group (IMWG) diagnostic criteria
* Measurable disease as defined by any of the following: (a) immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein \[M-protein\] level \>=1.0 gram/deciliter \[g/dL\] or urine M-protein level greater than or equal to (\>=) 200 milligram\[mg\]/24 hours\[hrs\]; or (b) IgA, IgD, or IgE multiple myeloma (serum M-protein level \>= 0.5 g/dL or urine M-protein level \>= 200 mg/24 hrs); or (c) light chain multiple myeloma (serum immunoglobulin free light chain \>=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio)
* Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
* Pretreatment clinical laboratory values must meet protocol-defined parameters during the Screening phase
* Man, who is sexually active with a woman of child-bearing potential and has not had a vasectomy, must agree to use a barrier method of birth control example (eg), either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the final dose of study drug
* Relapsed or refractory disease. Relapse is defined as progression of disease after an initial response to previous treatment, more than 60 days after cessation of treatment. Refractory disease is defined as less than (\<) 25 percent (%) reduction in M-protein or progression of disease during treatment or within 60 days after cessation of treatment
* Prior treatment with less than or equal to (\>=) 2 treatment lines of anti-myeloma therapy. Prior lines of therapy must include a proteasome inhibitor (PI) (eg, bortezomib, carfilzomib) and an immunomodulatory drug (IMiD) (example, thalidomide, lenalidomide, pomalidomide) in any order during the course of treatment. Each prior line of therapy may consist of one or more agents and may include induction, hematopoietic stem cell transplantation, and/or maintenance therapy. Radiotherapy, bisphosphonates, or a single short course of steroids is not considered a prior line of therapy

Exclusion Criteria:

* Participant has received daratumumab or other anti-cluster of differentiation 38 (anti-CD38) therapies previously
* Participant has received anti-myeloma treatment within 2 weeks before Cycle 1 Day 1
* Participant has previously received an allogenic stem cell transplant; or participant has received autologous stem cell transplantation (ASCT) within 12 weeks before Cycle 1 Day 1
* Participant has a history of malignancy (other than multiple myeloma) within 5 years before Cycle 1 Day 1 (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence)
* Participant is exhibiting clinical signs of meningeal involvement of multiple myeloma