906O - Phase 3 randomised study of daratumumab, bortezomib and dexamethasone (DVd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed or...

Date 09 October 2016
Event ESMO 2016 Congress
Session Haematological malignancies
Topics Haematologic Malignancies
Presenter Katja Weisel
Citation Annals of Oncology (2016) 27 (6): 313-327. 10.1093/annonc/mdw375
Authors K. Weisel1, A. Palumbo2, A. Chanan-Khan3, A.K. Nooka4, I. Spicka5, T. Masszi6, M. Beksac7, V. Hungria8, M. Munder9, M. Mateos10, T.M. Mark11, A. Spencer12, M. Qi13, J. Schecter14, H. Amin14, X. Qin15, W. Deraedt16, T. Ahmadi13, P. Sonneveld17
  • 1Dept Of Hematology, Oncology, Immunology, Rheumatology And Pulmonology, Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II, 72076 - Tuebingen/DE
  • 2Department Of Hematology, University of Torino, Torino/IT
  • 3Division Of Hematology & Medical Oncology, Mayo Clinic Florida, Jacksonville/US
  • 4Department Of Hematology And Medical Oncology, Winship Cancer Institute, Emory University, Atlanta/US
  • 5Clinical Department Of Haematology, 1st Medical Department, Charles University in Prague, Prague/CZ
  • 6Department Of Haematology And Stem Cell Transplantation, St László Hospital, Semmelweis University, Budapest/HU
  • 7Department Of Hematology, Ankara University, Ankara/TR
  • 8-, Irmandade Da Santa Casa De Misericordia De São Paulo, São Paulo/BR
  • 9Third Department Of Medicine, University Medical Center of the Johannes Gutenberg-University, Mainz/DE
  • 10-, University Hospital of Salamanca/IBSAL, Salamanca/ES
  • 11-, Weill Cornell Medical College, New York/US
  • 12Malignant Haematology And Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne/AU
  • 13-, Janssen Research & Development, LLC, Spring House/US
  • 14-, Janssen Research & Development, LLC, Raritan/US
  • 15-, Janssen Research & Development, LLC, Horsham/US
  • 16-, Janssen Research & Development, Beerse/BE
  • 17Department Of Hematology, Erasmus MC, Rotterdam/NL

Abstract

Background

Daratumumab (D), a human CD38 IgGκ monoclonal antibody, induces deep and durable responses with a favorable safety profile in RRMM pts. We report a pre-specified interim analysis of the first randomised, controlled study of D (CASTOR; NCT02136134).

Methods

Pts with ≥1 prior line of therapy were randomised (1:1) to 8 cycles q3w of bortezomib (V)/dexamethasone (d) (V: 1.3 mg/m2 sc on Days 1, 4, 8, 11; d: 20 mg po on Days 1, 2, 4, 5, 8, 9, 11, 12) ± D (16 mg/kg iv qw in Cycles 1-3, Day 1 of Cycles 4-8, then q4w until progression). Primary endpoint was PFS.

Results

498 pts (DVd, 251; Vd, 247) were randomised. Baseline demographics and disease characteristics were well balanced. Pts received a median of 2 prior lines of therapy (range 1-10). 76% received prior IMiD; 66% received prior V; 48% received prior PI and IMiD; 33% were IMiD-refractory; 32% were refractory to last line of prior therapy. With a median follow-up of 7.4 months, D significantly improved PFS (61% reduction in risk of progression), ORR, rates of ≥VGPR, rates of ≥CR, and delayed time to next therapy (Table). Median OS was NR in both groups. Most common (>25%) AEs (DVd/Vd) were thrombocytopenia (59%/44%), peripheral sensory neuropathy (47%/ 38%), diarrhea (32%/22%) and anemia (26%/31%). Most common grade 3/4 AEs (>10%) were thrombocytopenia (45%/33%), anaemia (14%/16%), neutropenia (13%/4%). 7%/9% of pts discontinued due to a TEAE. D-associated infusion-related reactions (45% of pts) mostly occurred during the first infusion; most were grade 1/2 (grade 3/4, 9%/0%). Additional subgroup analyses will be presented.

DVd Vd
PFS
Median, mo NR 7.2
HR (95% CI) 0.39 (0.28-0.53)
P

Conclusions

D in combination with Vd significantly improved PFS and ORR and delayed time to next therapy vs Vd alone. DVd doubled both VGPR and sCR/CR rates vs Vd alone. Safety of DVd is consistent with the known safety profile of D and Vd. The addition of D to Vd should be considered a new standard of care for RRMM pts currently receiving Vd alone.

Clinical trial identification

NCT02136134

Legal entity responsible for the study

N/A

Funding

Janssen Research & Development, LLC

Disclosure

K. Weisel: Honoraria from BMS, Celgene, Amgen, Onyx, Janssen, Novartis, Takeda; Consulting / Advisory role for BMS, Celgene, Amgen, Onyx, Janssen, Novartis, Takeda; Research Funding (for my institution) from Celgene and Janssen. A. Palumbo: Honoraria from Janssen; Consulting / Advisory role for Janssen; Research Funding (for my institution) from Janssen. A. Chanan-Khan: Research Funding (for my institution) for clinical research. A.K. Nooka: Consulting or advisory role for Novartis, Amgen, Spectrum Pharm. I. Spicka: Honoraria from Celgene, Janssen, Amgen; Consulting or advisory role for Celgene, Janssen, Amgen, BMS. T. Masszi: Consulting or advisory role for Takeda, Novartis, BMS, Janssen-Cilag. M. Beksac: Honoraria from Janssen-Cilag, Celgene, Amgen, Novartis, BMS; Speaker's Bureau for Janssen-Cilag, Celgene, Amgen, BMS. V. Hungria: Consulting or advisory role for Janssen, Takeda. M. Munder: Consulting or advisory role for Janssen, Amgen, Teva, Takeda; Travel, Accommodations, Expenses from Janssen, Takeda, BMS. M.-V. Mateos: Honoraria from Janssen, Celgene, Amgen, BMS, Takeda; Consulting or advisory role for Janssen, Celgene, Amgen, BMS, Takeda, Novartis. T.M. Mark: Stock or other ownership from Abbvie; Consulting or advisory role for Celgene, Takeda, Amgen, Janssen; Speakers Bureau for Celgene, Takeda, Bristol Myers Squibb, Amgen; Research funding (for my institution) from Celgene, Takeda, Amgen. A. Spencer: Honoraria from Janssen-Cilag; Consulting or advisory role for Janssen-Cilag; Speakers Bureau for Janssen-Cilag; Research Funding from Janssen-Cilag. M. Qi: Employment with Johnson & Johnson, Stock or other ownership in Johnson & Johnson J. Schecter: Employment with Janssen; Stock or other ownership from Janssen. H. Amin: Employment with Janssen Research & Development, LLC; Stock or other ownership from Johnson & Johnson, Merck, others via mutual funds. X. Qin: Employment with Janssen R&D. W. Deraedt: Employment with Johnson & Johnson; Stock or other ownership with Johnson & Johnson. T. Ahmadi: Employment with Janssen Research & Development; Stock or other ownership with Johnson & Johnson. P. Sonneveld: Honoraria from Amgen, Janssen, Celgene, Takeda; Consulting or advisory role for Amgen, Janssen, Celgene, Takeda; Research Funding (for my institution) from Amgen, Janssen, Celgene, Karyopharm.