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Activity of Anti-STEAP1 Antibody-Drug Conjugate in Patients With Metastatic Castration-Resistant Prostate Cancer


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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%).

KEY POINTS

  • The recommended phase II dose of DSTP3086S is 2.4 mg/kg every 3 weeks.
  • Partial response was observed in 4% of patients and stable disease was observed in 52%.

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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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