enoblituzumab (MGA271)

In pancreatic cancer, neuroblastoma, and glioblastoma xenograft models, CAR T cells incorporating the lead human binder Y111 were well tolerated and demonstrated superior antitumor activity compared with 376.96- and MGA271-based CARs. Y111 CAR treatment induced complete responses, tumor rejection, and significant survival benefits, identifying Y111 as a promising fully human B7-H3 CAR for solid tumors.

B7-H3 is expressed on a high proportion of pediatric solid tumors. While enoblituzumab could be safely administered at a weekly dose of 15 mg/kg, no objective tumor responses were observed. Alternative strategies to target B7-H3 in children with relapsed solid tumors should be considered.

P2, N=33, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jul 2025 --> Jul 2026

 The study highlights IL1B, IL15, CD276, NCR2, and CCL17 as key CRS genes in preinfusion CAR T-cell products. Their dysregulation activity may contribute to the increased inflammation noted in CRS, pointing to a loss of regulatory control. Bringing us closer to better patient outcomes, these findings not only suggest that these genes could serve as valuable biomarkers for predicting CRS but also open the way for the development of more precise treatments such as combining drugs such as enoblituzumab and canakinumab, which might assist in reducing CRS severity and making CAR T-cell therapy safer and more effective, ultimately improving patient lives.

P1, N=1, Terminated, Masonic Cancer Center, University of Minnesota | N=33 --> 1 | Trial completion date: Sep 2028 --> Aug 2024 | Suspended --> Terminated | Trial primary completion date: Sep 2026 --> Aug 2024; Product withdrawn from clinical development

P2, N=33, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2024 --> Jul 2025

Enoblituzumab, an immunotherapeutic agent targeting CD276, shows both safety and efficacy in activating T cells and oligodendrocyte-like cells against various cancers...Further investigations demonstrate that inhibiting ITGB6 restores sensitivity to PD1 antibodies in mice resistant to anti-PD1 treatment. In summary, our research reveals a resistance mechanism associated with immune checkpoint inhibitor therapy and identifies potential targets to overcome resistance in cancer treatment.

P2, N=33, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2024 --> Dec 2024

P2, N=0, Withdrawn, TJ Biopharma Co., Ltd. | N=160 --> 0 | Trial completion date: Dec 2024 --> Dec 2023 | Suspended --> Withdrawn | Trial primary completion date: Jun 2024 --> Dec 2023

P2, N=33, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2023 --> Jun 2024

P2, N=219, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting

P1, N=33, Suspended, Masonic Cancer Center, University of Minnesota | Recruiting --> Suspended