Daratumumab (DARA), a human IgGκ monoclonal antibody targeting CD38, is approved in the United States and Europe for use in patients with RRMM, as a monotherapy and in combination with bortezomib/dexamethasone or lenalidomide/dexamethasone. In a phase 1b study, DARA plus pomalidomide and low-dose dexamethasone (Pom-dex) demonstrated efficacy and tolerability in patients with RRMM. Here, the safety and efficacy of DARA plus Pom-dex is evaluated in a phase 3 study.
This is an ongoing, phase 3, multicenter, randomized, open-label study of DARA plus Pom-dex versus Pom-dex alone. Adults with RRMM who have received and responded to prior anti-myeloma therapy, including a proteasome inhibitor and a lenalidomide-containing regimen, and who have progressed on their last regimen are eligible. Patients who have received 1 prior line of therapy must have progressed ≤60 days of completing the lenalidomide-containing regimen. Patients will be randomized 1:1 to receive Pom 4 mg orally on Days 1-21 of a 28-day cycle plus dex 40 mg weekly (20 mg for patients ≥75 year of age), with or without intravenous DARA 16 mg/kg weekly in Cycles 1-2, every 2 weeks in Cycles 3-6, and monthly thereafter, until progression or unacceptable toxicity. To mitigate potential infusion-related reactions, all patients will receive pre-infusion medications (including dexamethasone, paracetamol, diphenhydramine, and an optional leukotriene inhibitor) and patients with a higher risk of respiratory complications will receive post-infusion medications (including diphenhydramine, a short-acting β2 adrenergic receptor agonist, and lung disease control medications). Safety evaluations will occur weekly during Cycles 1-2, every other week during Cycles 3-6, and monthly thereafter. Disease evaluations will occur monthly. The primary endpoint is progression-free survival. Secondary endpoints include safety, overall response rate, minimal-residual-disease-negative rate, duration of response, and overall survival. Approximately 302 patients will be enrolled across 10 countries.
Clinical trial identification
Legal entity responsible for the study
Janssen Research & Development, LLC
Funding provided by Janssen Research & Development
E. Terpos: Consultancy & Honoraria: Genesis, Bristol-Myers Squibb, Janssen, Takeda, Amgen. Honoraria: Celgene, Novartis. Research Funding: Genesis, Janssen, Amgen. M.A. Dimopoulos: Consultancy & Honoraria: Celgene, Janssen, Takeda, Amgen. E. Kastritis: Honoraria: Janssen, Celgene, Genesis, Takeda, Millennium-Takeda, Janssen-Cilag, Pharmacyclics. Research Funding: Novartis. J.M. Schecter: Employment & Equity: Janssen. J. Ukropec, E. Smith: Employment: Janssen. P. Sonneveld: Consultancy & Research Funding & Honoraria: Amgen, Celgene, Janssen, Karyopharm, Takeda.