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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
P. Kapoor, N. Nathwani, T. Jelinek, L. Pour, A. Perrot, MA. Dimopoulos, SY. Huang, I. Spicka, S. Chhabra, E. Lichtman, MV. Mateos, D. Kanagavel, L. Zhao, H. Guillemin-Paveau, S. Macé, H. van de Velde, PG. Richardson
Language English Country England, Great Britain
Document type Journal Article, Multicenter Study, Clinical Trial, Phase I
PubMed
38993150
DOI
10.1111/ejh.14270
Knihovny.cz E-resources
- MeSH
- ADP-ribosyl Cyclase 1 antagonists & inhibitors immunology MeSH
- Drug Resistance, Neoplasm MeSH
- Adult MeSH
- Antibodies, Monoclonal, Humanized administration & dosage therapeutic use adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Maximum Tolerated Dose MeSH
- Multiple Myeloma * drug therapy mortality MeSH
- Antibodies, Monoclonal administration & dosage therapeutic use adverse effects MeSH
- Recurrence MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase I MeSH
- Multicenter Study MeSH
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.
Department of Clinical Therapeutics National and Kapodistrian University of Athens Athens Greece
Department of Hematology Institut Universitaire du Cancer de Toulouse Toulouse France
Department of Hematology National Taiwan University Hospital Taipei Taiwan
Department of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic
Division of Hematology and Oncology Department of Medicine Mayo Clinic Arizona Phoenix Arizona USA
Division of Hematology Mayo Clinic Rochester Minnesota USA
Research and Development Sanofi Research and Development Cambridge Massachusetts USA
Research and Development Sanofi Research and Development Shanghai China
Research and Development Sanofi Research and Development Vitry sur Seine France
References provided by Crossref.org
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- $a 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.
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