P1, N=45, Terminated, Celgene | N=80 --> 45 | Active, not recruiting --> Terminated; Business objectives have changed

P1, N=80, Active, not recruiting, Celgene | Recruiting --> Active, not recruiting

We established a key role for IFNγ in AMG 330-mediated cytotoxicity against AML cells, and in rendering AML cells responsive to STING agonism. Here, we propose to improve the efficacy of CD33-targeting BsAbs by combining them with a STING agonist.

P1, N=45, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Nov 2029 --> Oct 2027 | Trial primary completion date: Nov 2028 --> Mar 2027

P1, N=45, Recruiting, Masonic Cancer Center, University of Minnesota | Not yet recruiting --> Recruiting

P1, N=3, Terminated, Institute of Hematology & Blood Diseases Hospital, China | N=18 --> 3 | Recruiting --> Terminated; It did not reach the expected results of clinical trial

P1, N=45, Not yet recruiting, Masonic Cancer Center, University of Minnesota | Initiation date: Oct 2024 --> Jan 2025

P1, N=45, Not yet recruiting, Masonic Cancer Center, University of Minnesota

This work demonstrates that CD33xIL15 fusion proteins are capable of targeting leukemic cells and stimulating local T cells in vitro and of concentrating in the tumour in AML xenografts. It also highlights the importance of 89Zr-immunoPET to guide the development and selection of tumour-targeted antibody-cytokine fusion proteins.

Showing for the first time that a membrane-proximal CAR is superior to a membrane-distal one in the setting of CD33 targeting, our results demonstrate the rationale for targeting membrane-proximal epitopes with high-affinity binders. We also demonstrate the importance of optimizing CAR T cells for functionality in settings of both low antigen density and clinically relevant patient-derived models.

CRS was mitigated with stepwise dosing of AMG 330, prophylactic dexamethasone, and early treatment with tocilizumab. Among 60 evaluable patients, eight achieved complete remission or morphologic leukemia-free state; of the 52 non-responders, 37% had ≥50% reduction in AML bone marrow blasts. AMG 330 is a promising CD33-targeted therapeutic strategy for R/R AML.

In addition to the anti-tumor effects of AMV564 on the clearance of MOLM13CG cells in vivo, similar effects were seen when primary CD33+ human AML cells were engrafted in NSG mice even when the human T cells made up only 2% of the peripheral blood cells and AML cells made up 98%. These studies suggest that AMV564 is a novel and effective bispecific diabody for the targeting of CD33+ AML that may provide long-term survival advantages in the clinic.