Subcutaneous Delivery of Daratumumab in Relapsed or Refractory Multiple Myeloma
Usmani SZ (1), Nahi H (2), Mateos MV (3), van de Donk NWCJ (4), Chari A (5), Kaufman JL (6), Moreau P (7), Oriol A (8), Plesner T (9), Benboubker L (10), Hellemans P (11), Masterson T (12), Clemens PL (13), Luo M (12), Liu K (14), San Miguel J (15)
(1) Levine Cancer Institute/Atrium Health, United States
(2) Karolinska Institute, Department of Medicine, Division of Hematology, Karolinska University Hospital at Huddinge, Sweden.
(3) Department of Hematology, University Hospital of Salamanca7IBSAL, Spain.
(4) Hematology, VU University Medical Center, Netherlands.
(5) Mount Sinai Hospital, United States.
(6) Hematology and Medical Oncology, Emory University Winship Cancer Institute, United States.
(7) Department of Hematology, Centre Hospitalier Universitaire de Nantes, France.
(8) Clinical Hematology, ICO - Hosp Germans Trias i Pujol, Spain.
(9) Hematology, Vejle Hospital, Denmark.
(10) Hematology & cell therapy, CHRU TOURS, France.
(11) Janssen Research & Development, LLC, Belgium.
(12) Janssen Research & Development, LLC, United States.
(13) Janssen R&D, United States.
(14) Biostatistics, Johnson & Johnson PRD, LLC, United States.
(15) Clinica Universidad de Navarra, Universidad de Navarra, Spain.
Daratumumab, a human monoclonal antibody targeting CD38, is approved as monotherapy and in combination regimens for patients with multiple myeloma (MM).
Currently, daratumumab is administered IV. The phase 1b PAVO (MMY1004) study evaluated subcutaneously administered daratumumab in combination with the recombinant human hyaluronidase PH20 enzyme (rHuPH20) in patients with relapsed or refractory MM (RRMM).
Part 1 of the study, reported here, evaluated a mix-and-deliver (MD) formulation of daratumumab and rHuPH20 (DARA-MD) administered by subcutaneous infusion. Patients received subcutaneous daratumumab per the approved IV monotherapy dosing schedule at 1,200 mg (n=8) or 1,800 mg (n=45).
Primary endpoints were safety and pharmacokinetics. The most common treatment emergent adverse events (TEAEs) with DARA-MD 1,200 mg were thrombocytopenia, upper respiratory tract infection (URTI), insomnia, and decreased appetite (37.5% each). Anemia (33.3%), URTI, pyrexia, and diarrhea (26.7% each) were the most common TEAEs with DARA-MD 1,800 mg. One patient in the 1,200 mg dose group (12.5%) and 11 patients in the 1,800 mg dose group (24.4%) experienced infusion-related reactions, which were generally grade 1-2 and typically occurred at the first infusion. The 1,800 mg dose achieved similar or greater serum concentrations compared to the 16 mg/kg IV dose. Overall response rates of 25.0% and 42.2% were achieved with 1,200 mg and 1,800 mg DARA-MD, respectively.
Subcutaneous administration of DARA-MD was well tolerated in patients with RRMM, with the 1,800 mg dose demonstrating pharmacokinetic concentrations and responses consistent with IV daratumumab in a similar patient population. This study was registered at www.clinicaltrials.gov as #NCT02519452.
CITA DEL ARTÍCULO Blood. 2019 Jul 3. pii: blood.2019000667. doi: 10.1182/blood.2019000667