Efficacy and safety of the randomized, open-label, non-inferiority, phase 3 study of subcutaneous (SC) versus intravenous (IV) daratumumab (DARA) administration in patients (pts) with relapsed or refractory multiple myeloma (RRMM): COLUMBA.

person Maria-Victoria Mateos University Hospital of Salamanca/IBSAL, Salamanca, Spain info_outline Maria-Victoria Mateos, Hareth Nahi, Wojciech Legiec, Sebastian Grosicki, Vladimir Vorobyev, Ivan Spicka, Vania TM Hungria, Sibirina Korenkova, Nizar J. Bahlis, Max Flogegard, Joan Blade, Philippe Moreau, Martin Kaiser, Shinsuke Iida, Jacob Laubach, Tahamtan Ahmadi, Dolly A. Parasrampuria, Lixian Peng, Ming Qi, Saad Zafar Usmani

Authors person Maria-Victoria Mateos University Hospital of Salamanca/IBSAL, Salamanca, Spain info_outline Maria-Victoria Mateos, Hareth Nahi, Wojciech Legiec, Sebastian Grosicki, Vladimir Vorobyev, Ivan Spicka, Vania TM Hungria, Sibirina Korenkova, Nizar J. Bahlis, Max Flogegard, Joan Blade, Philippe Moreau, Martin Kaiser, Shinsuke Iida, Jacob Laubach, Tahamtan Ahmadi, Dolly A. Parasrampuria, Lixian Peng, Ming Qi, Saad Zafar Usmani Organizations University Hospital of Salamanca/IBSAL, Salamanca, Spain, Karolinska Institute, Department of Medicine, Division of Hematology, Karolinska University Hospital at Huddinge, Stockholm, Sweden, Department of Hemato-Oncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland, Department of Hematology and Cancer Prevention, School of Public Health, Silesiam Medical University, Katowice, Poland, S.P.Botkin City Clinical Hospital, Moscow, Russian Federation, General Faculty Hospital, Prague, Czech Republic, Clinica São Germano, São Paulo, Brazil, Kiev Center for Bone Marrow Transplantation, Kiev, Ukraine, Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada, Department of Internal Medicine, Falun General Hospital, Falun, Sweden, IDIBAPS, Hospital Clinic de Barcelona, Barcelona, Spain, University Hospital of Nantes, Nantes, France, Division of Molecular Pathology, Institute of Cancer Research, Sutton, United Kingdom, Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, Department of Hematology and Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, Genmab US, Inc., Princeton, NJ, Janssen Research & Development, LLC, Spring House, PA, Janssen Research & Development, LLC, Raritan, NJ, Levine Cancer Institute/Atrium Health, Charlotte, NC Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: In a phase 1b trial, a SC formulation of DARA with recombinant human hyaluronidase PH20 (rHuPH20; ENHANZE drug delivery technology, Halozyme, Inc.) had adequate PK, low rates of infusion-related reactions (IRRs) and similar efficacy to DARA IV. This phase 3 study compared the efficacy, PK, and safety of DARA SC vs IV in pts with RRMM. Methods: DARA SC (1,800 mg DARA + rHuPH20 [2,000 U/mL]) and DARA IV (16 mg/kg IV) were given weekly for C1-2 (28-day cycles), every 2 weeks for C3-6, and every 4 weeks thereafter. DARA SC (15 mL) was given over 3-5 mins at alternating left/right abdominal sites. Pts (≥18 years) must have received ≥3 prior lines of therapy (LOT), including a PI and an IMiD, or were double refractory. Co-primary endpoints were ORR (analyzed by Farrington-Manning test, with non-inferiority = 60% retention of ORR) and pre-dose C3D1 DARA C trough (non-inferiority = lower bound of 90% CI for the ratio of the geometric means [GM] ≥80%). Results: 522 pts were randomized (n=263 SC; n=259 IV). Median age was 67 yrs. Median baseline body weight was 73 kg. Pts received a median of 4 LOT and 100% had received both PI and IMiD; 17% had high cytogenetic risk at baseline. Median follow-up was 7.5 mos. ORR was 41% for DARA SC and 37% for DARA IV. DARA SC retained at least 89% of the benefit of DARA IV (97.5% confidence). The ratio of GM of C trough for DARA SC over DARA IV was 108% (90% CI, 96%-122%). A significantly lower rate of IRRs was observed with DARA SC vs DARA IV (12.7% vs 34.5%; P <0.0001). Median duration of injection was 5 mins for DARA SC and median duration of infusion was 421/255/205 mins for the first/second/subsequent DARA IV infusions. Median PFS was 5.6 mos DARA SC vs 6.1 mos DARA IV (HR, 0.99; 95% CI, 0.78-1.26). Most common TEAEs (≥15%) were anemia, neutropenia, thrombocytopenia, and diarrhea. Primary reasons for treatment discontinuation included progressive disease (43% SC vs 44% IV) and AEs (7% SC vs 8% IV). Conclusions: Efficacy and PK co-primary endpoints were met, demonstrating non-inferiority of DARA SC to IV. DARA SC significantly decreased IRR rate and administration time, with a comparable safety profile to DARA IV. Clinical trial information: NCT03277105