Abstract CT320: An open-label, multicenter, phase Ib study of daratumumab in combination with backbone regimens in patients with multiple myeloma
Authors: Comenzo Raymond , Moreau Philippe , Mateos Maria-Victoria , Bladé Joan , Benboubker Lotfi , de la Rubia Javier , Facon Thierry , Fay Joseph , Qin Xiang , Masterson Tara , Schecter Jordan , Ahmadi Tahamtan , San-Miguel Jesus 
Published: August 2015

Abstract
Daratumumab (DARA) is a human anti-CD38 IgG1κ MAb in development for multiple myeloma (MM). DARA has shown single agent efficacy and manageable safety in patients with MM relapsed from or refractory (RR) to ≥2 prior therapy lines as well as in combination with lenalidomide (LEN) and dexamethasone (D) in relapsed or RR MM. This ongoing open-label, 4-arm, multicenter, phase Ib study evaluated safety and tolerability of DARA combined with other MM backbone treatments: bortezomib-dexamethasone (VD), bortezomib- thalidomide-dexamethasone (VTD), bortezomib-melphalan-prednisone (VMP), pomalidomide-dexamethasone (POM-D).
Newly diagnosed patients will be included in the VD (n = 6) and VTD (n = 12) arms (irrespective of transplant eligibility) and VMP arm (transplant ineligible; n = 12). Patients (up to 50) in the POM-D arm are RR to ≥2 lines of therapy including 2 consecutive cycles of LEN and V. Patients were treated with DARA 16 mg/kg and the approved label or standard of care of each backbone treatment: VD and VTD (DARA qw, 2 cycles; q3w, 16 cycles); VMP (DARA qw, 1 cycle; q3w, 8 cycles); POM-D (DARA qw, 2 cycles; q2w, 4 cycles; q4w remaining cycles). An independent data safety monitoring board evaluated safety and clinical responses.
Data from 25 subjects with newly diagnosed (VD [n = 6], VTD [n = 6], and VMP [n = 6]) and RR MM (POM-D [n = 7 safety; n = 6 efficacy]) are presented. There was no additional toxicity when DARA was added to backbone therapy, other than DARA-specific infusion related reactions (IRR). There were 11/25 subjects with IRRs; nearly all occurred on Cycle 1 Day 1, were grade 1 or 2 in severity, and resolved with supportive treatment. Median (range) numbers of DARA infusions were: VD, 9 (8-11); VTD, 8 (7-11); VMP, 12.5 (10-14); POM-D, 11 (1-17). All other adverse events (AEs) were consistent with those associated with the backbone agents. There were 4 serious (S) AEs (pneumonia, soft tissue infection, pre-renal failure [not DARA-related], indirect Coombs test interference [possibly DARA-related]) in the VTD arm and 1 SAE (infectious pneumonia [possibly DARA-related]) in the POM-D arm. Most common AEs were hematologic toxicity, likely related to backbone therapy.
The overall response rates were 100% in the VD, VTD and VMP arms and 50% in the POM-D arm. In the VD arm there were 3 very good partial responses (VGPR) and 3 partial responses (PR). In both the VMP and VTD arms there were 1 VGPR and 5 PRs. In the POM-D arm there was 1 stringent complete response, 2 VGPRs, 2 minimal responses and 1 patient with progressive disease. Median (range) times to first responses were: VD, 23.5 (22-44) days; VTD, 22 (22-43) days; VMP, 32.5 (22-135) days; POM-D, 31 (29-57) days. In VTD/VD patients who discontinued for ASCT mean stem cell yield was 6.25 × 106 CD34+ cells/kg.
DARA plus backbone MM therapies was well tolerated, with no significant additional toxicity and encouraging efficacy. The study is ongoing.
Citation Format: Raymond Comenzo, Philippe Moreau, Maria-Victoria Mateos, Joan Bladé, Lotfi Benboubker, Javier de la Rubia, Thierry Facon, Joseph Fay, Xiang Qin, Tara Masterson, Jordan Schecter, Tahamtan Ahmadi, Jesus San-Miguel. An open-label, multicenter, phase Ib study of daratumumab in combination with backbone regimens in patients with multiple myeloma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT320. doi:10.1158/1538-7445.AM2015-CT320