Subcutaneous Delivery of Daratumumab in Patients with RRMM
Description: Subcutaneous Delivery of Daratumumab in Patients with RRMM: PAVO, an Open-Label, Multicenter, Dose Escalation Phase Ib Study
Ajai Chari, MD
Mt. Sinai School of Medicine
New York, NY, USA
Background: Daratumumab (DARA), a CD38-targeted human monoclonal antibody, is approved as monotherapy and in combination with bortezomib (proteasome inhibitor; PI) or immunomodulatory drugs (IMiD; lenalidomide or pomalidomide) in pts with RRMM. DARA is administered intravenously (IV) and is associated with infusion related reactions (IRRs) in 46% of pts. We previously reported data from PAVO (NCT02519452), an open-label, multicenter, phase 1b study in RRMM, showing that subcutaneous (SC) delivery of DARA with recombinant human hyaluronidase enzyme (rHuPH20) by SC infusion of a mix and deliver formulation (DARA-MD) was well tolerated with low rates of IRRs (Usmani SZ, et al. ASH 2016; abstract 1149). DARA + rHuPH20 also demonstrated an efficacy profile consistent with IV DARA. We present updated data, including initial safety and efficacy findings from an additional cohort that received DARA co-formulated with rHuPH20 (DARA SC), which was delivered by manual SC injection.
Conclusions: SC administration of DARA + rHuPH20 was well tolerated, with lower than expected rates of IRRs in all groups, but particularly in those treated with DARA SC 1800 mg administered over only 3-5 minutes.
Authors: Ajai Chari, Hareth Nahi, Maria-Victoria Mateos, MD, PhD, Henk M. Lokhorst, Jonathan L. Kaufman, MD, Philippe Moreau, Albert Oriol, MD, Torben Plesner, MD, DSc, Lotfi Benboubker, MD, Peter Hellemans, Tara Masterson, Pamela L Clemens, Kevin Liu, Jesus F. San-Miguel, MD and Saad Z Usmani, MD