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.
Journal
European journal of haematology
Journal Volume
113
Journal Issue
5
Pages
593 - 605
ISSN
1600-0609
Date Issued
2024-11
Author(s)
Kapoor, Prashant
Nathwani, Nitya
Jelinek, Tomas
Pour, Ludek
Perrot, Aurore
Dimopoulos, Meletios-Athanasios
Spicka, Ivan
Chhabra, Saurabh
Lichtman, Eben
Mateos, Maria-Victoria
Kanagavel, Dheepak
Zhao, Liang
Guillemin-Paveau, Helene
Macé, Sandrine
van de Velde, Helgi
Richardson, Paul G
Abstract
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.
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).
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.
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.
Subjects
Fc‐engineered
anti‐CD38
daratumumab
isatuximab
multiple myeloma
relapsed/refractory
SDGs
Type
journal article