The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Non-Fucosylated CD70-directed Antibody

Geo Regions

Non-Fucosylated CD70-directed Antibody

PF-08046040, SGN-CD70 is an investigational compound. Its safety and efficacy have not been established.

Overview + Rationale

  • PF-08046040; SGN-CD70 is an investigational, humanized, nonfucosylated immunoglobulin G1 monoclonal antibody directed to CD701 
  • CD70 is a cell-surface ligand of the tumor necrosis factor superfamily, transiently expressed on activated B and T cells and mature dendritic cells2-4 whose receptor, CD27, is widely expressed on B, T, and natural killer cells3,4 
  • CD70 and CD27 are expressed on AML and MDS malignant blasts as well as on leukemic blasts that propagate the disease.1,5-8 
  • CD70 has limited expression in normal cells, making it an attractive target in myeloid malignancies2-6 
  • The nonfucosylated Fc region of PF-08046040; SGN-CD70 has increased affinity for activating FcγRIIIa receptors and minimal affinity for inhibitory FcγRIIb receptors, leading to enhanced Fc-mediated effector function1

Mechanism of Action

PF-08046040; SGN-CD70 is thought to engage an antitumor immune response through: 

  • Blockade of CD70/CD27-mediated proliferative signaling in malignant blast cells 2 
  • Antibody-dependent cellular phagocytosis2 
  • Enhanced antibody-dependent cellular cytotoxicity2 
  • Complement-dependent cytotoxicity2

Stage of Development

Small icon representing Hematologic Cancer
Myeloid Malignancies (R/R AML, MDS)
Phase 1 Monotherapy and Combination

AML: acute myeloid leukemia; MDS: myelodyspastic syndrome; R/R: relapsed/refractory

REFERENCES: 1. Diolaiti D. Blood. 2020: 23; 2. Grewal IS. Expert Opin Ther Targets. 2008: 341-51; 3. Aftimos P. Clin Cancer Res. 2017: 6411-20; 4. Cuesta-Mateos C. Front Immunol. 2018: 1936; 5. Schurch CM. Front Oncol. 2018: 152; 6. Riether C. J Exp Med. 2017: 359-80; 7. Syed K. Stem Cell Res Ther. 2020: 132; 8. Riether C. Nat Med. 2020: 1459-67; 9. NCT04227847. https://clinicaltrials.gov/ct2/show/NCT04227847. Accessed February 25, 2024.