Currently, two CD33xCD3 BiTE ® antibody constructs (AMG 330 & AMG 673) are being investigated in phase I dose escalation trials in patients with relapsed/refractory Acute Myeloid Leukemia (AML) with early evidence of acceptable safety and anti-leukemic activity (Ravandi et al., ASH 2020; Subklewe et al., EHA 2020). They support the notion that T cell co-signaling receptors like CD86 and PD-L1 modulate T-cell response in an early event manner. Prospective analyses in clinical trials are needed to validate the relevance of checkpoint molecule expression on target cells as a potential predictive biomarker for response.

3 years ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • CD33 (CD33 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • MAPK4 (Mitogen-Activated Protein Kinase 4) • CD86 (CD86 Molecule)

PD-L1 expression

eluvixtamab (AMG 330) • emerfetamab (AMG 673)

5years

Preliminary Results from a Phase 1 First-in-Human Study of AMG 673, a Novel Half-Life Extended (HLE) Anti-CD33/CD3 BiTE® (Bispecific T-Cell Engager) in Patients with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) (ASH 2019)

Preliminary data of AMG 673 dosed up to 72 µg provide early evidence of the molecule’s acceptable safety profile, drug tolerability, and anti-leukemic activity. An association was observed between PK/PD relationships that were consistent with the biological activity of AMG 673. These preliminary results support further dose escalation of the AMG 673 HLE BiTE® molecule in patients with R/R AML.

5 years ago

Clinical • P1 data

IL2RA (Interleukin 2 receptor, alpha)

emerfetamab (AMG 673)