vibecotamab (XmAb14045)

P2, N=42, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Blinatumomab plus standard chemotherapy or in combination with other treatments, such as Mini-Hyper-CVD and Inotuzumab Ozogamicin, improved disease-free survival (DFS) in B-ALL. In AML and related conditions, novel BsAbs like AFM28 (CD123xCD16A) and Vibecotamab (CD123xCD3) showed promising efficacy in heavily pretreated R/R AML and in MDS/CMML following the failure of treatment with hypomethylating agents (HMA). The meeting underscored the transformative potential of BsAbs, especially in ALL-focused trials, with ongoing research aiming to evaluate their safety and efficacy in broader patient populations and combination regimens. This summary highlights the latest progress in BsAb-based immunotherapy presented at the ASH 2024 meeting, held from December 7-10 in San Diego, California.

Conclusion Vibecotamab was safe and active in low-blast, high-risk myeloid diseases, with a response rate of 64% in MDS/CMML after HMA failure and 25% in MRD-positive AML. The clinical activity of vibecotamab, including in pts with prior venetoclax exposure and/or HSCT, and its lack of clinically significant myelosuppression provide rationale to combine it with other agents in AML, MDS, and CMML.

Response was associated with lower baseline blast count in blood and bone marrow (<25%) suggesting potential benefit. This trial was registered at www.clinicaltrials.gov as #NCT02730312.

Recent advances in molecular biology and genetics have led to the development of targeted agents, such as tagraxofusp (a recombinant fusion protein targeting CD123), anti-CD123 CAR-T cells, XmAb14045, and IMGN632. Lastly, this review provides a comprehensive overview of pDC neoplasms.

The trial is actively accruing at MD Anderson Cancer Center. Clinical trial information: NCT05285813.

In both whole blood cytokine release assays and in TDCC assays in which cytokine secretion was measured after target engagement, induction of TNF-α, IL-6, IFN-γ, and IL-2 by NGM936 was considerably lower than that induced by a vibecotamab biosimilar (CD123 x CD3). Finally, NGM936 induced a dose-dependent depletion of circulating tumor cells in a xenograft model in which irradiated, immunodeficient NSG mice were engrafted with human PBMCs and human ILT3+ AML cells. NGM936 thus represents a promising new treatment strategy for monocytic AML, with the potential to eliminate monocytic leukemia cells while minimizing the myelotoxicity associated with ablation of healthy bone marrow.

Vibecotamab demonstrated evidence of antileukemic activity in heavily pretreated patients with relapsed/refractory AML treated at the ≥0.75 µg/kg doses cohorts, with a 14% response rate. CRS was the most common toxicity but was generally manageable with premedications. The study is ongoing with further optimization of dose and schedule.