Initial Data Released on First-in-Human Phase 1 Trial with AMV564

In an oral presentation at the 23^rd Congress of European Hematology Association (EHA) in Stockholm, Amphivena Therapeutics released initial data from the dose escalation portion of the first-in-human phase 1 trial (AMV564-101, NCT03144245) evaluating AMV564 in patients with relapsed and/or refractory acute myeloid leukemia (AML).

AMV564 is a bivalent, bispecific (2X2) T-cell engager that binds CD33 and CD3 to moderate T-cell directed lysis of CD33-expressing myeloid cells; it is derived from human protein sequences. On approximately 90% of AML myeloblasts, CD33 is expressed.

“AMV564 was designed to produce a longer half-life than the small monovalent bispecific T-cell engagers,” stated Eric J. Feldman MD, chief medical officer at Amphivena in a recent statement. “Here, at EHA, the initial data presentation represents our first clinical proof-of-concept of T-cell engagement, T-cell activation, and leukemic cytoreduction in patients with heavily pre-treated, chemotherapy resistant AML.”

The first-in-human dose escalation and dose expansion phase 1 trial, AMV564-101, was created to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AMV564 in patients with relapsed and/or refractory AML (NCT03144245). In the data shared from the phase 1 trial, which included 17 patients treated within 5 cohorts, AMV564 demonstrated engaging and activating functions in T-cells, resulting in leukemic cytoreduction.

“AMV564 is a potent T-cell engager that is well tolerated by patients with AML,” added Peter Westervelt, MD, PhD, professor of medicine at Washington University in St Louis, and a principal investigator for the study, presented on behalf of the study team.

For the study, AMV564 is being administered by continuous intravenous infusion, for 14 consecutive days for up to 2 induction cycles. Those included in the study are adults with relapsed and/or refractory AML after 1 to 2 prior induction regimens (with a standard anthracycline-based regimen or hypomethylating agent) with no more than 2 prior salvage regimens.

Primary outcome measures include safety and tolerability as measured by the number of participants with adverse events in the dose escalation and expansion stage, and efficacy as measured by the proportion of participants who achieve complete remission, complete remission with incomplete recovery, or partial remission. Both primary measures are being measured in the time frame of 36 months.

“The pharmacokinetics are unprecedented with a gradual rise to steady state drug levels that may help mitigate cytokine release syndrome,” Dr. Westervelt added. “The 0%, 30-day mortality rate in this high-risk population of AML patients is extremely encouraging, and we are seeing evidence of anti-leukemic activity even at very low doses.”

Currently, the phase 1 study is open at Washington University, MD Anderson Cancer Center, and Weill-Cornell Medical College. The anticipated completion date for the phase 1 trial is February 20, 2020.