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

Authors	KAPOOR Prashant NATHWANI Nitya JELINEK Tomas POUR Luděk PERROT Aurore DIMOPOULOS Meletios-Athanasios HUANG Shang-Yi SPICKA Ivan CHHABRA Saurabh LICHTMAN Eben MATEOS Maria-Victoria KANAGAVEL Dheepak ZHAO Liang GUILLEMIN-PAVEAU Helene MACE Sandrine HELGI van de Velde RICHARDSON Paul G
Year of publication	2024
Type	Article in Periodical
Magazine / Source	European Journal of Haematology
MU Faculty or unit	Faculty of Medicine
Citation
web	https://onlinelibrary.wiley.com/doi/10.1111/ejh.14270
Doi	https://doi.org/10.1111/ejh.14270
Keywords	anti-CD38; daratumumab; Fc-engineered; isatuximab; multiple myeloma; relapsed/refractory
Description	Objectives: 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 naive 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 5-75 mg/kg. Most common treatment-emergent adverse events were infusion-related reactions in 703% (26/37) patients. Grade >= 3 thrombocytopenia was reported in 486% (18/37). Overall response rate was 70% in anti-CD38 mAb naive and 4% in anti-CD38 pre-treated patients, with a median progression-free survival of 762 (95%CI: 2858; not calculable) months and 279 (95%CI: 1150; 4172) months and, respectively. Conclusions: The efficacy of SAR442085 was promising in anti-CD38 mAb naive 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.