In a phase I trial reported in the Journal of Clinical Oncology, Danila et al found that the antibody-drug conjugate DSTP3086S, which targets the six-transmembrane epithelial antigen of the prostate 1 (STEAP1), had acceptable safety and evidence of activity in patients with metastatic castration-resistant prostate cancer.

The agent includes an anti-STEAP1 antibody linked to the antimitotic agent monomethyl auristatin E. As noted by the investigators, STEAP1 is commonly expressed in prostate cancer, but has limited expression in nonprostate tissue.

Safety

A total of 77 patients received the agent at intravenous doses of 0.3 to 2.8 mg/kg every 3 weeks in a dose-escalation phase followed by an expansion phase at the selected phase II dose. During dose escalation, two patients experienced dose-limiting grade 3 transaminitis. The selected phase II dose of 2.8 mg/kg every 3 weeks—which was given to the first 10 patients in the expansion cohort—was reduced to 2.4 mg/kg in the remaining 39 patients due to frequent need for dose reduction.

Treatment-related adverse events of grade 3 or 4 occurred in 31% of patients, with the most common being peripheral neuropathy and fatigue (4% each). The most common treatment-related adverse events of any grade were fatigue (56%), peripheral neuropathy (51%), nausea (38%), constipation (35%), decreased appetite (34%), diarrhea (26%), and vomiting (25%).

Activity

Among all 77 patients receiving every-3-week treatment, 11 (14%) had prostate-specific antigen (PSA) reduction of 50% or more. Among 62 patients receiving ≥ 2 mg/kg, PSA responses were observed in 1 (14%) of 7 patients receiving a dose of 2.25 mg/kg; 5 (13%) of 39 receiving a dose of 2.4 mg/kg; and 5 (31%) of 16 receiving a dose of 2.8 mg/kg (overall, 11 of 62 [18%]). Of 46 patients with evaluable disease, 2 (4%) had a partial response and 24 (52%) had stable disease according to RECIST criteria. Among 38 patients with circulating tumor cells ≥ 5/7.5 mL of blood, 19 (50%) had reductions to < 5/7.5 mL, including 16 (59%) of 27 patients receiving a dose of ≥ 2 mg/kg.

The investigators concluded, “DSTP3086S has acceptable safety at the recommended phase II dose level of 2.4 mg/kg once every 3 weeks. Antitumor activity at doses between 2.25 and 2.8 mg/kg once every 3 weeks supports the potential benefit of treating STEAP1-expressing metastatic castration-resistant prostate cancer with an STEAP1-targeting antibody-drug conjugate.”

Daniel C. Danila, MD, of the Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Genentech. For full disclosures of the study authors, visit jco.ascopubs.org.