A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: Dara SC; Drug: Dara IV

Study type: Interventional

Funder types: Industry

Identifiers

NCT03277105

2017-000206-38 (EudraCT Number)

CR108342

54767414MMY3012 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to show that subcutaneous (SC) administration of daratumumab co-formulated with recombinant human hyaluronidase PH20 (Dara SC) is non-inferior to intravenous (IV) administration of daratumumab (Dara IV) in terms of the overall response rate (ORR) and maximum trough concentration (Ctrough).

Full description

The study population will consist of adults diagnosed with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD. The study consists of 3 phases: a screening phase (up to 28 days), a treatment phase, and a follow-up phase. Efficacy, pharmacokinetics, immunogenicity, biomarkers and safety will be assessed at scheduled time. Follow-up will continue until the end of the data collection period, approximately 24 months after the last participant was randomized or when the median overall survival for both arms has been reached, whichever occurs first. The primary hypotheses is that the ORR and maximum Ctrough for Dara SC 1800 milligram (mg) are not inferior to the ORR and maximum Ctrough, respectively, for Dara IV 16 mg per kilogram (mg/kg) in participants with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD.

Enrollment: 522 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Evidence of a response (Partial response [PR] or better based on investigator's determination of response by international myeloma working group [IMWG] criteria) to at least 1 prior treatment regimen

• Received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to [>=] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (>=2 cycles or 2 months of treatment) in any order during the course of treatment (except for participants who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). 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/day [mg/day] for 4 days) would not be considered prior lines of therapy

• Documented multiple myeloma as defined by the criteria below:

  1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria

  2. Measurable disease at Screening as defined by any of the following:

     1. Serum M-protein level >=1.0 gram per deciliter (g/dL) or urine M-protein level >=200 mg/24 hours; or
     2. Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

• Meet the clinical laboratory criteria as specified in the protocol

• Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization

Exclusion criteria

• Received daratumumab or other anti-CD38 therapies previously
• Received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) before treatment
• Received autologous stem cell transplant within 12 weeks before the date of randomization, or the participant has previously received allogeneic stem cell transplant (regardless of timing)
• Plans to undergo a stem cell transplant prior to progression of disease on this study (these participants should not be enrolled to reduce disease burden prior to transplant)
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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522 participants in 2 patient groups

Dara SC

Experimental group

Description:

Participants will receive a fixed dose of daratumumab as 1800 milligram (mg) subcutaneously (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks.

Treatment:

Drug: Dara SC

Dara IV

Active Comparator group

Description:

Participants will receive daratumumab for intravenous infusion (Dara IV) 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks on Day 1 in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks. For Participants still receiving treatment with Dara-IV at the time of Protocol Amendment 4 the duration of infusion may be shortened to a 90-minute infusion or participants will have the option to switch to Dara 1800 mg subcutaneous (SC) on Day 1 of any cycle, at the discretion of the investigator.

Treatment:

Drug: Dara IV

Drug: Dara SC