Enoblituzumab appears safe and effective in high-risk prostate cancer

Primary endpoints of safety and efficacy were met in the Phase 2 trial (NCT02923180) of enoblituzumab, a novel immunotherapy agent targeting B7-H3 for the treatment of patients with high-risk prostate cancer.^1.2 The findings were published in natural medicine.

Patients received enoblituzumab via 6 weekly infusions prior to their surgery. The median duration of follow-up was 30 months.

“Enoblituzumab appears to be safe and appears to activate the immune system in a way that involves both T cells and myeloid cells. This means that if these results can be replicated in a larger randomized study, it opens up the possibility that combining this therapy with local therapies with curative intent such as surgical removal of the prostate or radiation therapy would allow this drug to potentially kill micrometastatic disease lurking elsewhere in the body, and therefore prevent significant numbers of men to suffer from recurring disease. This could be a paradigm shift in prostate cancer,” Eugene Shenderov, MD, PhD, said in a press release about the findings.² Shenderov is an assistant professor of oncology at Johns Hopkins School of Medicine in Baltimore, Maryland.

The single-arm phase 2 study enrolled 32 patients with high-risk or very high-risk prostate cancer who were scheduled for prostatectomy. A total of 47% of patients had prostate-specific antigen (PSA) levels greater than 10 ng/mL at diagnosis, and 50% had Gleason class 5 disease.

Patients received enoblituzumab via 6 weekly infusions prior to their surgery. The median duration of follow-up was 30 months. The co-primary endpoints of the study were safety and undetectable PSA (PSA₀) at 12 months after surgery.

The 12-month follow-up results showed that the co-primary endpoint of PSA₀ rate was achieved, with 21 patients (66%) showing no signs of residual disease. The median PSA recurrence-free survival time was not reached after 30 months of median follow-up.

The treatment also met its safety endpoint, with 6 patients (12%) experiencing Grade 3 adverse events (AEs) and no Grade 4 AEs. Common AEs included fatigue (72%), neurological symptoms such as headache, dizziness and paresthesia (44%), as well as flu and cold symptoms (41%), most of which were grade 1. All patients were alive at the time Datas. cut.

“The results are exciting but exploratory and need to be confirmed in larger study cohorts. However, these findings in patients with high-risk prostate cancer and the broader need for effective immunotherapeutic strategies in cancers cancers warrant the development of multi-pronged approaches that include targeting B7-H3 to optimize antitumor activity in prostate cancers and other solid malignancies,” said lead author Emmanuel S Antonarakis, MD, in the press release Antonarakis is the Clark Endowed Professor of Medicine and Director of GU Oncology for the Masonic Cancer Center at the University of Minnesota.

A randomized trial is planned to assess the clinical activity of enoblituzumab against current standards of care in patients newly diagnosed with prostate cancer.

The references

1. Shenderov E, De Marzo AM, Lotan TL, et al. Neoadjuvant enoblituzumab in localized prostate cancer: a single-arm phase 2 trial. Night with. Published online April 3, 2023. Accessed April 7, 2023. https://doi.org/10.1038/s41591-023-02284-w

2. A safe and promising new immunotherapy agent against high-risk prostate cancers. Press release. Johns Hopkins Medicine. April 6, 2023. Accessed April 7, 2023. https://www.newswise.com/articles/novel-immunotherapy-agent-safe-shows-promise-against-high-risk-prostate-cancers?ta=home