Subcutaneous Delivery of Daratumumab in Relapsed or Refractory Multiple Myeloma

Saad Z Usmani, Hareth Nahi, Maria-Victoria Mateos, Niels W C J van de Donk, Ajai Chari, Jonathan L Kaufman, Philippe Moreau, Albert Oriol, Torben Plesner, Lotfi Benboubker, Peter Hellemans, Tara Masterson, Pamela L Clemens, Man Luo, Kevin Liu, Jesus San Miguel

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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. 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 according to the approved IV monotherapy dosing schedule at 1200 mg (n = 8) or 1800 mg (n = 45). Primary end points were safety and pharmacokinetic (PK) variables. The most common treatment-emergent adverse events with DARA-MD 1200 mg were thrombocytopenia, upper respiratory tract infection, insomnia, and decreased appetite (37.5% each). Anemia (33.3%), upper respiratory tract infection, pyrexia, and diarrhea (26.7% each) were the most common treatment-emergent adverse events with DARA-MD 1800 mg. One patient in the 1200-mg dose group (12.5%) and 11 patients in the 1800-mg dose group (24.4%) experienced infusion-related reactions, which were generally grade 1/2 and typically occurred at the first infusion. The 1800 mg dose achieved similar or greater serum concentrations compared with the 16 mg/kg IV dose. Overall response rates of 25.0% and 42.2% were achieved with 1200-mg and 1800-mg DARA-MD, respectively. Subcutaneous administration of DARA-MD was well tolerated in patients with relapsed or refractory MM, with the 1800-mg dose exhibiting PK concentrations and responses consistent with IV daratumumab in a similar patient population. This study was registered at www.clinicaltrials.gov as #NCT02519452.

OriginalsprogEngelsk
TidsskriftBlood
Vol/bind134
Udgave nummer8
Sider (fra-til)668-677
ISSN0006-4971
DOI
StatusUdgivet - 22. aug. 2019

Fingeraftryk

Hyaluronoglucosaminidase
Pharmacokinetics
Enzymes
daratumumab
Safety
Serum
Population

Citer dette

Usmani, S. Z., Nahi, H., Mateos, M-V., van de Donk, N. W. C. J., Chari, A., Kaufman, J. L., ... San Miguel, J. (2019). Subcutaneous Delivery of Daratumumab in Relapsed or Refractory Multiple Myeloma. Blood, 134(8), 668-677. https://doi.org/10.1182/blood.2019000667
Usmani, Saad Z ; Nahi, Hareth ; Mateos, Maria-Victoria ; van de Donk, Niels W C J ; Chari, Ajai ; Kaufman, Jonathan L ; Moreau, Philippe ; Oriol, Albert ; Plesner, Torben ; Benboubker, Lotfi ; Hellemans, Peter ; Masterson, Tara ; Clemens, Pamela L ; Luo, Man ; Liu, Kevin ; San Miguel, Jesus. / Subcutaneous Delivery of Daratumumab in Relapsed or Refractory Multiple Myeloma. I: Blood. 2019 ; Bind 134, Nr. 8. s. 668-677.
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title = "Subcutaneous Delivery of Daratumumab in Relapsed or Refractory Multiple Myeloma",
abstract = "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. 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 according to the approved IV monotherapy dosing schedule at 1200 mg (n = 8) or 1800 mg (n = 45). Primary end points were safety and pharmacokinetic (PK) variables. The most common treatment-emergent adverse events with DARA-MD 1200 mg were thrombocytopenia, upper respiratory tract infection, insomnia, and decreased appetite (37.5{\%} each). Anemia (33.3{\%}), upper respiratory tract infection, pyrexia, and diarrhea (26.7{\%} each) were the most common treatment-emergent adverse events with DARA-MD 1800 mg. One patient in the 1200-mg dose group (12.5{\%}) and 11 patients in the 1800-mg dose group (24.4{\%}) experienced infusion-related reactions, which were generally grade 1/2 and typically occurred at the first infusion. The 1800 mg dose achieved similar or greater serum concentrations compared with the 16 mg/kg IV dose. Overall response rates of 25.0{\%} and 42.2{\%} were achieved with 1200-mg and 1800-mg DARA-MD, respectively. Subcutaneous administration of DARA-MD was well tolerated in patients with relapsed or refractory MM, with the 1800-mg dose exhibiting PK concentrations and responses consistent with IV daratumumab in a similar patient population. This study was registered at www.clinicaltrials.gov as #NCT02519452.",
author = "Usmani, {Saad Z} and Hareth Nahi and Maria-Victoria Mateos and {van de Donk}, {Niels W C J} and Ajai Chari and Kaufman, {Jonathan L} and Philippe Moreau and Albert Oriol and Torben Plesner and Lotfi Benboubker and Peter Hellemans and Tara Masterson and Clemens, {Pamela L} and Man Luo and Kevin Liu and {San Miguel}, Jesus",
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day = "22",
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language = "English",
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Usmani, SZ, Nahi, H, Mateos, M-V, van de Donk, NWCJ, Chari, A, Kaufman, JL, Moreau, P, Oriol, A, Plesner, T, Benboubker, L, Hellemans, P, Masterson, T, Clemens, PL, Luo, M, Liu, K & San Miguel, J 2019, 'Subcutaneous Delivery of Daratumumab in Relapsed or Refractory Multiple Myeloma', Blood, bind 134, nr. 8, s. 668-677. https://doi.org/10.1182/blood.2019000667

Subcutaneous Delivery of Daratumumab in Relapsed or Refractory Multiple Myeloma. / Usmani, Saad Z; Nahi, Hareth; Mateos, Maria-Victoria; van de Donk, Niels W C J; Chari, Ajai; Kaufman, Jonathan L; Moreau, Philippe; Oriol, Albert; Plesner, Torben; Benboubker, Lotfi; Hellemans, Peter; Masterson, Tara; Clemens, Pamela L; Luo, Man; Liu, Kevin; San Miguel, Jesus.

I: Blood, Bind 134, Nr. 8, 22.08.2019, s. 668-677.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Subcutaneous Delivery of Daratumumab in Relapsed or Refractory Multiple Myeloma

AU - Usmani, Saad Z

AU - Nahi, Hareth

AU - Mateos, Maria-Victoria

AU - van de Donk, Niels W C J

AU - Chari, Ajai

AU - Kaufman, Jonathan L

AU - Moreau, Philippe

AU - Oriol, Albert

AU - Plesner, Torben

AU - Benboubker, Lotfi

AU - Hellemans, Peter

AU - Masterson, Tara

AU - Clemens, Pamela L

AU - Luo, Man

AU - Liu, Kevin

AU - San Miguel, Jesus

N1 - Copyright © 2019 American Society of Hematology.

PY - 2019/8/22

Y1 - 2019/8/22

N2 - 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. 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 according to the approved IV monotherapy dosing schedule at 1200 mg (n = 8) or 1800 mg (n = 45). Primary end points were safety and pharmacokinetic (PK) variables. The most common treatment-emergent adverse events with DARA-MD 1200 mg were thrombocytopenia, upper respiratory tract infection, insomnia, and decreased appetite (37.5% each). Anemia (33.3%), upper respiratory tract infection, pyrexia, and diarrhea (26.7% each) were the most common treatment-emergent adverse events with DARA-MD 1800 mg. One patient in the 1200-mg dose group (12.5%) and 11 patients in the 1800-mg dose group (24.4%) experienced infusion-related reactions, which were generally grade 1/2 and typically occurred at the first infusion. The 1800 mg dose achieved similar or greater serum concentrations compared with the 16 mg/kg IV dose. Overall response rates of 25.0% and 42.2% were achieved with 1200-mg and 1800-mg DARA-MD, respectively. Subcutaneous administration of DARA-MD was well tolerated in patients with relapsed or refractory MM, with the 1800-mg dose exhibiting PK concentrations and responses consistent with IV daratumumab in a similar patient population. This study was registered at www.clinicaltrials.gov as #NCT02519452.

AB - 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. 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 according to the approved IV monotherapy dosing schedule at 1200 mg (n = 8) or 1800 mg (n = 45). Primary end points were safety and pharmacokinetic (PK) variables. The most common treatment-emergent adverse events with DARA-MD 1200 mg were thrombocytopenia, upper respiratory tract infection, insomnia, and decreased appetite (37.5% each). Anemia (33.3%), upper respiratory tract infection, pyrexia, and diarrhea (26.7% each) were the most common treatment-emergent adverse events with DARA-MD 1800 mg. One patient in the 1200-mg dose group (12.5%) and 11 patients in the 1800-mg dose group (24.4%) experienced infusion-related reactions, which were generally grade 1/2 and typically occurred at the first infusion. The 1800 mg dose achieved similar or greater serum concentrations compared with the 16 mg/kg IV dose. Overall response rates of 25.0% and 42.2% were achieved with 1200-mg and 1800-mg DARA-MD, respectively. Subcutaneous administration of DARA-MD was well tolerated in patients with relapsed or refractory MM, with the 1800-mg dose exhibiting PK concentrations and responses consistent with IV daratumumab in a similar patient population. This study was registered at www.clinicaltrials.gov as #NCT02519452.

U2 - 10.1182/blood.2019000667

DO - 10.1182/blood.2019000667

M3 - Journal article

VL - 134

SP - 668

EP - 677

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -

Usmani SZ, Nahi H, Mateos M-V, van de Donk NWCJ, Chari A, Kaufman JL et al. Subcutaneous Delivery of Daratumumab in Relapsed or Refractory Multiple Myeloma. Blood. 2019 aug 22;134(8):668-677. https://doi.org/10.1182/blood.2019000667