Daratumumab (DARA) is a human IgGκ anti-CD38 monoclonal antibody with a direct on-tumor and immunomodulatory mechanism of action. DARA (16 mg/kg administered intravenously [IV]) is approved in many countries as monotherapy and in combination with standard of care (SOC) treatment regimens for patients with relapsed/refractory (RR) multiple myeloma (MM) and newly diagnosed MM. Three phase 3 studies have now demonstrated that DARA in combination with SOC treatment doubles complete response (CR) rates, triples minimal residual disease-negative rates, and reduces the risk of progression or death by at least 50% vs SOC alone. The median durations of the first, second, and subsequent DARA IV infusions are 7.0, 4.3, and 3.4 hours, respectively. To determine whether the duration of infusion can be shortened without compromising the safety or efficacy of daratumumab, an open-label, multicenter, phase 1b clinical trial (PAVO; NCT02519452) was conducted to evaluate a subcutaneous (SC) formulation of DARA with recombinant human hyaluronidase enzyme PH20 (rHuPH20; ENHANZE® drug delivery technology, Halozyme, Inc.) in patients with RRMM. Part 1 of the study revealed that a mix-and-deliver SC administration was well tolerated, with low rates of infusion-related reactions (IRRs) and similar efficacy to DARA IV (Usmani et al. ASH 2016; abstract 1149). Here, we present updated safety and efficacy findings from Part 2 of the PAVO study, where a concentrated, pre-mixed SC co-formulation of DARA and rHuPH20 (DARA SC) was evaluated in patients with RRMM.
DARA SC enabled dosing in 3-5 minutes and improves patient convenience. DARA SC was well-tolerated in patients with RRMM with low rates of IRRs and no new safety signals compared with DARA IV. Over 50% of patients responded to treatment and median PFS has not been reached after median follow-up of 6.5 months. These data inform ongoing phase 3 studies of DARA SC in RRMM (including a non-inferiority study of DARA SC vs DARA IV [COLUMBA; NCT03277105]), smoldering multiple myeloma, and AL amyloidosis.
Ajai Chari, MD, Maria-Victoria Mateos, MD, PhD, Niels W. C. J. van de Donk, Jonathan L Kaufman, MD, Philippe Moreau, Albert Oriol, MD, Torben Plesner, MD, DSc, Lotfi Benboubker, MD, Hareth Nahi, MD, PhD, Jie Tang, Peter Hellemans, Brenda Tromp, MSc, Pamela L Clemens, PhD, Andrew Farnsworth, Jesus F San-Miguel, MD, PhD and Saad Z. Usmani, MD
ABOUT AJAI CHARI, MD
Dr. Ajai Chari is an Associate Professor of Medicine, Director of Clinical Research in the Multiple Myeloma Program, and the Associate Director of Clinical Research, Mt Sinai Cancer Clinical Trials Office in New York. His main areas of focus are plasma cell disorders including multiple myeloma, AL amyloidosis, POEMS syndrome, plasmacytoma, and monoclonal gammopathies of undetermined significance (MGUS). View Dr. Ajai Chari’s full biography here.