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.

Autor: Kapoor P; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Nathwani N; Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, California, USA., Jelinek T; Department of Hematooncology, University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic., Pour L; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic., Perrot A; Department of Hematology, Institut Universitaire du Cancer de Toulouse, Toulouse, France., Dimopoulos MA; Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece., Huang SY; Department of Hematology, National Taiwan University Hospital, Taipei, Taiwan., Spicka I; First Department of Medicine, Department of Hematology, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic., Chhabra S; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic Arizona, Phoenix, Arizona, USA., Lichtman E; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Department of Medicine, Division of Hematology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Mateos MV; Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain., Kanagavel D; Research and Development, Sanofi, Research and Development, Vitry-sur-Seine, France., Zhao L; Research and Development, Sanofi, Research and Development, Shanghai, China., Guillemin-Paveau H; Research and Development, Sanofi, Research and Development, Vitry-sur-Seine, France., Macé S; Research and Development, Sanofi, Research and Development, Vitry-sur-Seine, France., van de Velde H; Research and Development, Sanofi, Research and Development, Cambridge, Massachusetts, USA., Richardson PG; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Multiple Myeloma Center, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: European journal of haematology [Eur J Haematol] 2024 Nov; Vol. 113 (5), pp. 593-605. Date of Electronic Publication: 2024 Jul 12.
DOI: 10.1111/ejh.14270
Abstrakt: 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 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.
(© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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