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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
Participants will receive Daratumumab mixed with rHuPH20 in part 1 and co-formulated with rHuPH20 in part 2 and part 3 administered via SC administration once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and every 4 weeks in subsequent cycles.
Participants will receive Recombinant Human Hyaluronidase \[rHuPH20\]) mixed with Daratumumab in part 1 and co-formulated with Daratumumab in part 2 and part 3 administered as SC administration once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and every 4 weeks in subsequent cycles.
Unnamed facility
Atlanta, Georgia, United States
Unnamed facility
New York, New York, United States
Unnamed facility
Charlotte, North Carolina, United States
Unnamed facility
Philadelphia, Pennsylvania, United States
Unnamed facility
Vejle, Denmark
Unnamed facility
Nantes, France
Unnamed facility
Tours, France
Unnamed facility
Amsterdam, Netherlands
Unnamed facility
Badalona, Spain
Unnamed facility
Pamplona, Spain
...and 2 more locations
Serum Trough Concentrations (Ctrough) of Daratumumab
Ctrough: the concentration prior to study drug administration.
Time frame: Up to cycle 3 (each cycle 28 days) Day 1
Part 1, 2 and 3: Number of Participants with Adverse Events (AEs) and Serious AEs
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Screening up to follow-up (30 days after last dose administration) (Approximately up to 3.4 years)
Part 1, 2 and 3: Serum Concentration of Daratumumab and Recombinant Human Hyaluronidase (rHuPH20) (Plasma) Antibodies
Serum levels of antibodies to Daratumumab and rHuPH20 for evaluation of potential immunogenicity.
Time frame: Approximately 2 years
Part 1, 2 and 3: Percentage of Participants with Complete Response (CR)
CR is Defined as the proportion of Participants achieving CR (including sCR) according to the International Myeloma Working Group (IMWG) criteria.
Time frame: Approximately 2 years
Part 1, 2 and 3: Percentage of Participants With Overall Response Rate (ORR)
Overall response rate is defined as the percentage of participants who achieve complete response, stringent complete response (sCR), partial response or very good partial response (VGPR) according to the International Myeloma Working Group criteria, during or after study treatment.
Time frame: Approximately 2 years
Part 1, 2 and 3: Duration of Response (DR)
The DR is time from date of initial documentation of response (PR or better) to date of first documented PD, as defined by IMWG criteria.
Time frame: Approximately 2 years
Part 1, 2 and 3: Time to Response
Time to response is defined as the time from the date of first dose of study treatment to the date of the first documentation of observed response (CR or PR or better than PR)
Time frame: Approximately 2 years
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