"[This] could be a paradigm shift in prostate cancer,” says Eugene Shenderov, MD, PhD.
The co-primary safety and efficacy end points have been met in the phase 2 trial (NCT02923180) of enoblituzumab, a novel B7-H3 targeting immunotherapy agent for the treatment of patients with high-risk prostate cancer.1,2 The findings were published in Nature Medicine.
“Enoblituzumab appears safe and seems to activate the immune system in a way that involves both T-cells and myeloid cells. What this means is if these results can be replicated in a larger, randomized study, it opens the possibility that combining this therapy with local, curative-intent therapies like surgical prostate removal or radiation therapy would allow this drug to potentially kill micrometastatic disease hiding elsewhere in the body, and therefore prevent a significant number of men from experiencing recurring disease. That could be a paradigm shift in prostate cancer,” said Eugene Shenderov, MD, PhD, in a news release on the findings.2 Shenderov is an assistant professor of oncology at the 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. In total, 47% of patients had a prostate-specific antigen (PSA) level greater than 10 ng/mL at diagnosis, and 50% had Gleason grade group 5 disease.
Patients received enoblituzumab via 6 once-weekly infusions prior to their surgery. Median follow-up time was 30 months. The co-primary end points of the study were safety and undetectable PSA level (PSA0) at 12 months following surgery.
Findings at the 12-month follow-up showed that the co-primary end point of PSA0 rate was met, with 21 patients (66%) having no sign of residual disease. The median PSA recurrence-free survival time was not reached after 30 months median follow-up.
The treatment also met its safety end point, with 6 patients (12%) experiencing grade 3 adverse events (AEs) and no instances of grade 4 AEs. Common AEs included fatigue (72%), neurological symptoms such as headache, dizziness, and paresthesia (44%), and flu and cold-like symptoms (41%), with most tending to be grade 1. All patients were alive at data cut-off.
“The findings are exciting but exploratory and need to be confirmed in larger study cohorts. However, these results in high-risk prostate cancer patients, and the broader need for immunotherapeutic strategies with efficacy in prostate cancers, provide justification to further develop multipronged approaches that include targeting B7-H3 to optimize antitumor activity in prostate cancers and other solid malignancies,” said senior author Emmanuel S. Antonarakis, MD, in the news release. Antonarakis is the Clark Endowed Professor of Medicine and director of GU Oncology for the University of Minnesota Masonic Cancer Center.
A randomized trial is being planned to assess the clinical activity of enoblituzumab compared with current standards of care in patients newly diagnosed with prostate cancer.
1. Shenderov E, De Marzo AM, Lotan TL, et al. Neoadjuvant enoblituzumab in localized prostate cancer: a single-arm, phase 2 trial. Nat Med. Published online April 3, 2023. Accessed April 7, 2023. https://doi.org/10.1038/s41591-023-02284-w
2. Novel immunotherapy agent safe, shows promise against high-risk prostate cancers. News 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