%0 Journal Article
%T An open-label, first-in-human, single agent, dose escalation study for the evaluation of safety and efficacy of SAR442085 in patients with relapsed or refractory multiple myeloma.
%A Kapoor P
%A Nathwani N
%A Jelinek T
%A Pour L
%A Perrot A
%A Dimopoulos MA
%A Huang SY
%A Spicka I
%A Chhabra S
%A Lichtman E
%A Mateos MV
%A Kanagavel D
%A Zhao L
%A Guillemin-Paveau H
%A Macé S
%A van de Velde H
%A Richardson PG
%J Eur J Haematol
%V 0
%N 0
%D 2024 Jul 12
%M 38993150
%F 3.674
%R 10.1111/ejh.14270
%X OBJECTIVE: Cluster of differentiation 38 (CD38) is a key target on multiple myeloma (MM) cells. This multi-centre, Phase 1, single-agent study (NCT04000282) investigated SAR442085, a novel fragment crystallisable (Fc)-modified anti-CD38 monoclonal antibody (mAb), with enhanced affinity towards Fc-gamma receptor on effector cells in patients with relapsed and/or refractory (RR) MM.
METHODS: This study comprised two parts: Part-A (dose-escalation involving anti-CD38 mAb pre-treated and naïve patients) and Part-B (dose expansion). Primary endpoints were maximum tolerated dose and recommended Phase 2 dose (RP2D).
RESULTS: Thirty-seven heavily pre-treated patients were treated in Part A. Part-B (dose-expansion) was not studied. Seven dose-limiting toxicities were reported at DL3, DL5, DL6, and DL7. RP2D was determined to be 5-7·5 mg/kg. Most common treatment-emergent adverse events were infusion-related reactions in 70·3% (26/37) patients. Grade ≥3 thrombocytopenia was reported in 48·6% (18/37). Overall response rate was 70% in anti-CD38 mAb naïve and 4% in anti-CD38 pre-treated patients, with a median progression-free survival of 7·62 (95%CI: 2·858; not calculable) months and 2·79 (95%CI: 1·150; 4·172) months and, respectively.
CONCLUSIONS: The efficacy of SAR442085 was promising in anti-CD38 mAb naïve patients but did not extend to the larger cohort of anti-CD38 mAb pre-treated patients. This observation, along with transient high-grade thrombocytopenia, could potentially limit its clinical use.