B7 homolog 3 (B7-H3; CD276), a tumor-associated antigen and possible immune checkpoint, is highly expressed in prostate cancer (PCa) and is associated with early recurrence and metastasis. Enoblituzumab is a humanized, Fc-engineered, B7-H3-targeting antibody that mediates antibody-dependent cellular cytotoxicity. In this phase 2, biomarker-rich neoadjuvant trial, 32 biological males with operable intermediate to high-risk localized PCa were enrolled to evaluate the safety, anti-tumor activity and immunogenicity of enoblituzumab when given before prostatectomy. The coprimary outcomes were safety and undetectable prostate-specific antigen (PSA) level (PSA0) 1 year postprostatectomy, and the aim was to obtain an estimate of PSA0 with reasonable precision. The primary safety endpoint was met with no notable unexpected surgical or medical complications, or surgical delay. Overall, 12% of patients experienced grade 3 adverse events and no grade 4 events occurred. The coprimary endpoint of the PSA0 rate 1 year postprostatectomy was 66% (95% confidence interval 47–81%). The use of B7-H3–targeted immunotherapy in PCa is feasible and generally safe and preliminary data suggest potential clinical activity. The present study validates B7-H3 as a rational target for therapy development in PCa with larger studies planned. The ClinicalTrials.gov identifier is NCT02923180.
|Original language||English (US)|
|Number of pages||10|
|State||Published - Apr 2023|
Bibliographical noteFunding Information:
E.S. is a paid consultant to GT Biopharma, Guidepoint Global, FirstThought and GLG, and receives institutional research funding from MacroGenics, Inc. E.S.A. is a paid consultant/advisor to and/or received institutional research funding from Janssen, Astellas, Sanofi, Dendreon, Genentech, Pfizer, Amgen, Lilly, Bayer, Tokai, Clovis, AstraZeneca, Novartis and BMS; and patent and royalty rights from QIAGEN for AR-V7 in prostate cancer. P.M. and F.C. are employees of MacroGenics, Inc. and receive stock options. K.S., A.M.W., S.E.C. and B.H. are employees of NanoString Technologies Inc. and receive stock options. P.F. is an employee of Adaptive Biotechnologies and receives stock options. S.H. is an employee of CDI Labs and receives stock options. C.G.D. is an employee of Janssen and receives stock options. A.M.D.M. is a paid consultant to Merck and Cepheid and received institutional research funding from Janssen. The remaining authors report no competing interests.
We thank patients and their families for participation in this ClinicalTrials.gov-registered clinical trial (NCT02923180). This investigator-initiated trial at Johns Hopkins was funded by MacroGenics, Inc. which also provided study drug free of cost. The sponsor was involved in data collection and analysis, but was not involved in study design, decision to publish or preparation of the manuscript. The authors retain full responsibility for the content. This work was partially supported by the National Institutes of Health Cancer Center Support (grant no. P30 CA006973 to E.S., E.S.A. and A.M.D.M.); NCI SPORE in Prostate Cancer (grant/award no. P50CA58236 to A.M.D.M.); Prostate Cancer Foundation Young Investigator Award (to E.S.); Department of Defense grant (nos. W81XWH-16-PCRP-CCRSA and W81XWH-19-1-0511 to E.S., and W81XWH ‐18‐2‐0015 to A.M.D.M.); and the Bloomberg–Kimmel Institute for Cancer Immunotherapy (E.S., D.M.P. and E.S.A.). We thank M. Caldwell for his assistance with the Tempus xE assay bioinformatics pipeline preparation.
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.