Phase II study of daratumumab (DARA) monotherapy in patients with ≥ 3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius).

Lymphoma and Plasma Cell Disorders
Session Type and Session Title: 
Oral Abstract Session, Myeloma
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr LBA8512)
Sagar Lonial, Brendan M. Weiss, Saad Zafar Usmani, Seema Singhal, Ajai Chari, Nizar J. Bahlis, Andrew Belch, Amrita Y. Krishnan, Robert A. Vescio, María-Victoria Mateos, Amitabha Mazumder, Robert Z. Orlowski, Heather J Sutherland, Joan Blade, Emma Catherine Scott, Huaibao Feng, Imran Khan, Clarissa M. Uhlar, Tahamtan Ahmadi, Peter Michael Voorhees; Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA; Division of Hematology & Oncology, Department of Medicine, Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Levine Cancer Institute/Carolinas Healthcare System, Charlotte, NC; Robert H. Lurie Comprehensive Cancer Center, Division of Hem./Onc., Northwestern University Feinberg School of Medicine, Chicago, IL; Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY; Tom Baker Cancer Center - University of Calgary, Calgary, AB, Canada; Cross Cancer Institute, Department of Medical Oncology, Edmonton, AB, Canada; Department Hematology and Hematopoietic Stem Cell Transplant, City of Hope, Duarte, CA; Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA; University Hospital of Salamanca/IBSAL, Salamanca, Spain; NYU Perlmutter Cancer Center, New York, NY; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX; Leukemia/Bone Marrow Transplant Program, University of British Columbia, Vancouver, BC, Canada; IDIBAPS, Hospital Clinic de Barcelona, Barcelona, Spain; Knight Cancer Institute, Oregon Health and Science University, Portland, OR; Janssen Research & Development, Spring House, PA; Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC

Abstract Disclosures


Background: DARA, a human anti-CD38 IgG1κ mAb, has single agent activity and is well-tolerated in rel/ref MM (Lokhorst HM et al. ASCO 2014). This ongoing phase 2 study (NCT01985126) evaluated DARA monotherapy in the FDA breakthrough therapy designation population: MM patients with ≥ 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or double refractory to a PI and IMiD. Preliminary results are reported. Methods: MMY2002 is a 2-part, open-label, international, multicenter study. In part 1 stage 1, 34 patients were randomized to DARA 8 mg/kg (n = 18) q4w or 16 mg/kg (n = 16) qw x 8 wk, q2w x 16 wk, then q4w in a Simon-2-stage design to determine the most effective dose. Subsequently, 90 additional patients were enrolled in the 16 mg/kg DARA group. The primary endpoint was overall response rate (ORR) by independent review (IRC). Results: Data for the 16 mg/kg DARA group are presented (n = 106). Baseline characteristics: median time since diagnosis, 4.8 y; median prior treatment lines, 5; 75% ISS ≥ 2. Refractory to: last line of therapy, 96%; last PI and IMiD, 95%; pomalidomide, 63%: carfilzomib, 48%; alkylating agents, 78%. Adverse events (AE; ≥ 20%) were fatigue (39.6%), anemia (33.0%), nausea (29.2%), thrombocytopenia (25.5%), back pain (22.6%), neutropenia (22.6%), cough (20.8%). Infusion-related reactions (IRR, 42.5%) were mainly grade 1/2 during first infusion (grade 3 4.7%; no grade 4). No patients discontinued study due to IRRs; 5 (4.7%) discontinued treatment due to AEs. None of these AEs were assessed by the investigator to be DARA-related. ORR (IRC assessed) was 29.2%, with 3 sCR, 10 VGPR, and 18 PR with a 7.4 month median duration of response. ORR was consistent across clinically relevant subgroups. Median time to progression was 3.7 months. Median overall survival has not been reached and the estimated 1-year OS rate is 65%. After a median follow up of 9.4 months 14/31 (45.2%) of responders remain on therapy. Conclusions: In a heavily pre-treated MM population (95% refractory to last PI and IMiD), DARA at 16 mg/kg showed meaningful durable single agent activity, with deep responses and a favorable safety profile. Clinical trial information: NCT01985126