Enoblituzumab is a humanized, Fc-engineered, monoclonal antibody targeting B7-H3, which mediates ADCC. Shenderov et al. performed a phase 2 trial assessing enoblituzumab therapy before surgery in 32 previously untreated patients with prostate cancer. Treatment was well tolerated (12% grade 3 adverse events), and treatment did not affect surgery timing or outcomes. The PSA0 rate at 1 year post-surgery was 66%, and 50% of patients had Gleason score downgrade. Tumor and peripheral blood TCR sequencing revealed an association with PSA0 outcomes, and TME analysis revealed immune inflammation upregulation, including increases in CD8+ T cells.
Contributed by Maartje Wouters
ABSTRACT: 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 (PSA(0)) 1 year postprostatectomy, and the aim was to obtain an estimate of PSA(0) 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 PSA(0) 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.
Author Info: (1) Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Eugene.Shenderov@jhmi.edu. The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins
Author Info: (1) Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Eugene.Shenderov@jhmi.edu. The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine, Baltimore, MD, USA. Eugene.Shenderov@jhmi.edu. (2) Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA. (3) Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA. (4) Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, MD, USA. (5) Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA. (6) Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, MD, USA. (7) Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. (8) Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA. (9) Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA. (10) MacroGenics, Inc., Rockville, MD, USA. (11) MacroGenics, Inc., Rockville, MD, USA. (12) NanoString Technologies Inc., Seattle, WA, USA. (13) NanoString Technologies Inc., Seattle, WA, USA. (14) NanoString Technologies Inc., Seattle, WA, USA. (15) NanoString Technologies Inc., Seattle, WA, USA. (16) Adaptive Biotechnologies, Seattle, WA, USA. (17) CDI Labs, Baltimore, MD, USA. (18) Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA. (19) Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA. (20) Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA. (21) Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. (22) Immuno-Oncology, Janssen, Horsham, PA, USA. (23) Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA. The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine, Baltimore, MD, USA. (24) Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA. The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine, Baltimore, MD, USA. University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA.
