A phase II multi-arm study of magrolimab combinations in patients with relapsed/refractory multiple myeloma

Future Oncol. 2023 Jan;19(1):7-17. doi: 10.2217/fon-2022-0975. Epub 2023 Feb 13.

Abstract

Magrolimab is a monoclonal antibody that blocks CD47, a 'do not eat me' signal overexpressed on tumor cells. CD47 is overexpressed in multiple myeloma (MM), which contributes to its pathogenesis. Preclinical studies have shown that CD47 blockade induces macrophage activation, resulting in elimination of myeloma cells, and that there is synergy between magrolimab and certain anticancer therapies. These findings suggest that magrolimab-based combinations may have a therapeutic benefit in MM. This phase II study investigates magrolimab in combination with commonly used myeloma therapies in patients with relapsed/refractory MM and includes a safety run-in phase followed by a dose-expansion phase. Primary end points include the incidence of dose-limiting toxicities and adverse events (safety run-in) and the objective response rate (dose expansion).

Trial registration: ClinicalTrials.gov NCT04892446.

Keywords: CD47; bortezomib; carfilzomib; daratumumab; dexamethasone; immunotherapy; magrolimab; multiple myeloma; pomalidomide.

Plain language summary

Magrolimab is a therapy that blocks a ‘do not eat me’ signal overexpressed by certain cancers, including multiple myeloma (MM) cells. Studies have shown that blocking this signal leads to destruction of myeloma cells and that this cancer-killing effect may be increased by combining magrolimab with certain additional anticancer therapies. These findings suggest that magrolimab-based combinations may have a therapeutic benefit in MM. This study is investigating magrolimab in combination with commonly used myeloma therapies in patients with MM who have persistent disease despite prior treatment. Goals of the trial include assessing safety and response to treatment. Clinical Trial Registration: NCT04892446 (ClinicalTrials.gov).

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • CD47 Antigen
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Dexamethasone / therapeutic use
  • Humans
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / pathology
  • Neoplasm Recurrence, Local / pathology

Substances

  • magrolimab
  • CD47 Antigen
  • Dexamethasone

Associated data

  • ClinicalTrials.gov/NCT04892446