A Study of Daratumumab With the Addition of Recombinant Human Hyaluronidase (rHuPH20) for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma
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
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.
Dr. Morie Gertz from the Mayo Clinic Rochester, talks about the multiple myeloma clinical trials and abstracts presented at the annual American Society of Clinical Oncologists (ASCO) meeting in Chicago, IL.
Dr. Paul Richardson from the Dana-Farber Cancer Institute, talks about the multiple myeloma clinical trials and abstracts presented at the annual American Society of Clinical Oncologists (ASCO) meeting in Chicago, IL.
Dr. Sagar Lonial from the Winship Cancer Institute, talks about the multiple myeloma clinical trials and abstracts presented at the annual American Society of Clinical Oncologists (ASCO) meeting in Chicago, IL.
Phase III randomized controlled study of daratumumab, bortezomib, and dexamethasone (DVd) versus bortezomib and dexamethasone (Vd) in patients (pts) with relapsed or refractory multiple myeloma (RRMM): CASTOR study.