The immune checkpoint protein B7-H3 may be a potential new target in treatment-resistant prostate cancers, according to two studies presented recently at the European Society for Medical Oncology (ESMO) Congress 2021.
“Virtually every prostate cancer cell expresses some degree of B7-H3, which appears to be associated with rapid recurrence and earlier metastasis,” said Eugene Shenderov, MD, PhD, the lead author of both studies and an Assistant Professor of Oncology at Johns Hopkins Medicine.
Eugene Shenderov, MD, PhD
Enoblituzumab in Localized Disease
The first study (Abstract 627P) was a phase II trial of the anti–B7-H3 antibody enoblituzumab in 32 patients with localized prostate cancer who were scheduled to undergo prostatectomy. Patients received six weekly infusions of enoblituzumab at 15 mg/kg prior to surgery. Investigators then compared biopsy samples taken at diagnosis with the removed prostates to study changes to tumor tissue. Preprostatectomy prostate-specific antigen (PSA) declines of more than 10% were observed in 34% of patients (95% confidence interval [CI] = 20%–52%). PSA0 at 1-year postprostatectomy was seen in 66% of patients (95% CI = 48%–80%), and median time to PSA recurrence was not reached. Gleason grade group upgrade, no change, and downgrade was observed in 12.5%, 37.5%, and 50% of patients respectively. Additionally, there were more functional immune cells seen after treatment with enoblituzumab, indicating a change in the tumor microenvironment.
MGC018: An Anti–B7-H3 Antibody-Drug Conjugate
The second study (Abstract 620P) was a phase I study evaluating an experimental agent called MGC018 in solid tumors. MGC018 is an antibody-drug conjugate that contains an anti–B7-H3 antibody with an anticancer agent called duocarmycin, which allows the drug to deliver the duocarmycin payload directly to tumor cells expressing B7-H3. Among the patients studied were 39 with metastatic castration-resistant prostate cancer who had undergone prior treatment with chemotherapy and hormonal therapies. They received increasing doses of the therapy every 3 weeks. Among 39 patients who were evaluated by the cut-off date, 21 patients (54%) had a PSA reduction of more than 50% from baseline, and 4 of 16 patients who were evaluated for radiographic response had a partial response. Over half of all patients studied in the entire cohort (including patients with non–small cell lung cancer, melanoma, triple-negative breast cancer, and head and neck squamous cell carcinoma) experienced grade 3 or higher adverse events, indicating toxicity will need to be reduced in further drug development. The study authors wrote, “Results to date have demonstrated a manageable safety profile with evidence of clinical activity by PSA and tumor responses in metastatic castration-resistant prostate cancer.”
Everything seems to point to the fact that B7-H3 is potentially an important therapeutic target in the prostate cancer setting.— Eugene Shenderov, MD, PhD
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“Everything seems to point to the fact that B7-H3 is potentially an important therapeutic target in the prostate cancer setting,” said Dr. Shenderov. He and his colleagues are planning a clinical trial to study combination therapies targeting B7-H3 to determine if that further boosts immune response.
Disclosure: The research was supported by Conquer Cancer, Macrogenics, the Prostate Cancer Foundation, and the Department of Defense Congressionally Directed Medical Research Programs. For full disclosures of the study authors, visit oncologypro.esmo.org.
