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ASCO 2016: PAVO study -- Dr. Saad Usmani

A Study of Daratumumab With the Addition of Recombinant Human Hyaluronidase (rHuPH20) for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma

06.06.16

Author(s): 

Hareth Nahi, Peter Hellemans, Tara J. Masterson, Pamela L. Clemens, Tahamtan Ahmadi, Jesus San Miguel, María-Victoria Mateos, Saad Zafar Usmani; Karolinska Institute and the Department of Medicine, Karolinska University Hospital, Huddinge, Sweden; Janssen Research & Development, Beerse, Belgium; Janssen Research & Development, Spring House, PA; Clinica Universidad de Navarra, Pamplona, Spain; University Hospital of Salamanca/IBSAL, Salamanca, Spain; Levine Cancer Institute/Carolinas Health Care System, Charlotte, NC

Abstract Disclosures

Background: 

Daratumumab (DARA), a human CD38 IgG1 monoclonal antibody, is approved in the US for patients with relapsed/refractory multiple myeloma (RR MM; ≥ 3 lines including a PI and IMiD or PI/IMiD double refractory). DARA has promising efficacy and a favorable safety profile as a monotherapy and in combination. The recommended DARA dose and schedule is 16 mg/kg intravenous (IV) weekly (QW) for 8 weeks, every 2 weeks (Q2W) for 16 weeks, and every 4 weeks (Q4W) thereafter. Subcutaneous (SC) formulations of therapeutic antibodies with recombinant human hyaluronidase (rHuPh20) have been approved in Europe. Here, SC DARA delivery combined with rHuPh20 is being evaluated. Methods: This is an ongoing phase 1b open-label, dose-escalation study of DARA given SC or IV in patients with symptomatic RR MM who have received ≥ 2 prior therapies. In Part 1, approximately 8 patients will enroll in each sequential cohort treated with doses of DARA-rHuPh20 SC (1200 mg-30,000 U; 1800 mg-45,000 U; subsequent doses to be determined) given QW in Cycles 1-2 (28 days/cycle), Q2W in Cycles 3-6, and Q4W thereafter. In the absence of dose limiting toxicity in > 2 patients in Cycle 1, patients will be assigned to the next dose cohort; up to 5 additional dose cohorts may be evaluated. A Study Evaluation Team will review pharmacokinetics (PK) and safety data to determine dose escalation and the recommended part 2 dose (RP2D). Part 2 will evaluate PK, safety, and efficacy of SC DARA. Approximately 80 patients will be randomized 1:1 to receive DARA-rHuPh20 SC at RP2D or DARA IV (1200 mg). The primary endpoints are serum trough concentrations of DARA just prior to Cycle 3 Day 1 and clinical safety. All patients will be observed for ≥ 72 hours and ≥ 24 hours, respectively, after the first SC infusion and, if necessary, after subsequent doses. To prevent/manage infusion-related reactions, pre- and post-infusion medications (steroids, paracetamol, montelukast, and antihistamines) similar to those administered with IV DARA will be given. Approximately 128 patients will be enrolled at 12 sites in 6 countries. The first patient was enrolled in October 2015.

Clinical trial information: NCT02519452


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