Data from the first-in-human phase I dose-escalation study (NCT03144245) of AMV564, a novel bivalent, bispecific CD33/CD3 targeted immunotherapy that binds both CD33 and the invariant CD3ε on T-cell receptor in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) was presented at the 23rd Congress of the European Hematology Association, Stockholm, Sweden by Peter Westervelt from Washington University School of Medicine, St. Louis, US. The main objectives of the study were to evaluate the safety, tolerability, and preliminary anti-leukemic activity of AMV564.
A total of 17 R/R AML patients (median age = 72 years, range; 24–84) have been enrolled in one of five dose escalation cohorts (three patients per cohort) including 0.5, 1.5, 5.0, 15, and 50 mcg/day for 14 days continuous infusion.
Key finding as of June 7th, 2018:
- No dose-limiting toxicity observed
- Most common treatment-emergent grade ≥ 3 adverse event was febrile neutropenia in 20% of patients
- Thirty-day mortality rate: 0%
Preliminary leukemic activity observed at doses ≤ 50 mcg
- Increased cytokine and antigen markers of T-cell activation were observed following AMV564 administration
- Reductions in bone marrow blasts ranging from 13%–38% were observed in 10 of 16 evaluable patients
- Two of 3 patients with progression after cycle 1 had a reduction in bone marrow blasts after cycle 2
In summary, the speaker concluded by stating that “AMV564 is well-tolerated and can be administered without the need for incremental dosing and/or pre-medication”. AMV564 also demonstrated anti-leukemic activity at low doses in patients with R/R AML.