Initial data on AMV564 in patients with relapsed/refractory AML

AMV564-101 is a phase 1, first-in-human, dose escalation and dose expansion trial designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AMV564 in patients with relapsed or refractory acute myeloid leukaemia (AML) after 1-2 prior induction regimens (with a standard anthracycline-based regimen or hypomethylating agent) and no more than 2 prior salvage regimens. Prof. Gail Roboz (Weill Cornell Medicine, USA) highlighted initial data from the dose-escalation portion of data from 33 patients treated within 9 cohorts, demonstrating favourable safety profile and initial efficacy data that AMV564 is active [1].

AMV564 is a bivalent, bispecific CD33/CD3 T cell engager with 2 binding sites for CD3 (expressed on T cells) and 2 binding sites for CD33 (highly expressed in myeloid-derived suppressor cells and on >95% of AML blasts). AMV564 brings T cells together with the CD33+ AML blast cell (see Figure) leading to T cell activation, proliferation and differentiation as well as cytokine release and T cell-mediated cell death of the CD33+ cells without affecting monocytes and neutrophils.

Figure: Bivalent binding action of AMV564, bispecific antibody for CD33/CD3. Modified from [2]



“While this is a phase 1 study,” Prof. Roboz said, “we believe that AMV564 has demonstrated promising monotherapy activity, including a CR, CRi, and PR, and evidence of durability in a high-risk, older patient population on a 14-day dosing regimen. The data shows that AMV564 is well tolerated with no dose-limiting toxicities in doses up to 250 µg and only grade 1 and grade 2 cytokine release syndrome distinguishing the safety of AMV564 from other drugs in development for myeloid malignancies.”

There were only limited grade 1 and 2 events. A lead-in dose schedule is now being utilised to continue the escalation up to 450 µg. Some responses and stabilisation of the disease for up to 7 months were observed.

1. 
   
   1. Westerveldt P, et al. Abstract S877. 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.
   2. Hoseini SS, et al. Blood Advances 2018, 2(11), 1250-1258.

 



Posted on 9 August 20194 March 2021