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.

1st Department of Medicine Department of Hematology 1st Faculty of Medicine Charles University and General Hospital Prague Czech Republic

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 Hematooncology University Hospital Ostrava and University of Ostrava Ostrava Czech Republic

Department of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic

Department of Medical Oncology Dana Farber Cancer Institute Jerome Lipper Multiple Myeloma Center Boston Massachusetts USA

Department of Medicine Division of Hematology University of North Carolina at Chapel Hill Chapel Hill North Carolina USA

Division of Hematology and Oncology Department of Medicine Mayo Clinic Arizona Phoenix Arizona USA

Division of Hematology Mayo Clinic Rochester Minnesota USA

Hospital Universitario de Salamanca Instituto de Investigacion Biomedica de Salamanca University of Salamanca Salamanca Spain

Judy and Bernard Briskin Center for Multiple Myeloma Research City of Hope Comprehensive Cancer Center California USA

Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill Chapel Hill North Carolina 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

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