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

  • Eur J Haematol. 2024 Nov;113(5):593-605. doi: 10.1111/ejh.14270.
Prashant Kapoor  1 ,  Nitya Nathwani  2 ,  Tomas Jelinek  3 ,  Ludek Pour  4 ,  Aurore Perrot  5 ,  Meletios-Athanasios Dimopoulos  6 ,  Shang-Yi Huang  7 ,  Ivan Spicka  8 ,  Saurabh Chhabra  9 ,  Eben Lichtman  10  11 ,  Maria-Victoria Mateos  12 ,  Dheepak Kanagavel  13 ,  Liang Zhao  14 ,  Helene Guillemin-Paveau  13 ,  Sandrine Macé  13 ,  Helgi van de Velde  15 ,  Paul G Richardson  16
Affiliations
  • 1. Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
  • 2. Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, California, USA.
  • 3. Department of Hematooncology, University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic.
  • 4. Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
  • 5. Department of Hematology, Institut Universitaire du Cancer de Toulouse, Toulouse, France.
  • 6. Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece.
  • 7. Department of Hematology, National Taiwan University Hospital, Taipei, Taiwan.
  • 8. First Department of Medicine, Department of Hematology, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic.
  • 9. Division of Hematology and Oncology, Department of Medicine, Mayo Clinic Arizona, Phoenix, Arizona, USA.
  • 10. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • 11. Department of Medicine, Division of Hematology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • 12. Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.
  • 13. Research and Development, Sanofi, Research and Development, Vitry-sur-Seine, France.
  • 14. Research and Development, Sanofi, Research and Development, Shanghai, China.
  • 15. Research and Development, Sanofi, Research and Development, Cambridge, Massachusetts, USA.
  • 16. Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Multiple Myeloma Center, Boston, Massachusetts, USA.
PMID: 38993150 DOI: 10.1111/ejh.14270
Abstract

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.

Keywords
Fc‐engineered; anti‐CD38; daratumumab; isatuximab; multiple myeloma; relapsed/refractory.
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