Phase I study of DSTP3086S, an antibody-drug conjugate targeting six-transmembrane epithelial antigen of prostate 1, in metastatic castration-resistant prostate cancer Journal Article


Authors: Danila, D. C.; Szmulewitz, R. Z.; Vaishampayan, U.; Higano, C. S.; Baron, A. D.; Gilbert, H. N.; Brunstein, F.; Milojic-Blair, M.; Wang, B.; Kabbarah, O.; Mamounas, M.; Fine, B. M.; Maslyar, D. J.; Ungewickell, A.; Scher, H. I.
Article Title: Phase I study of DSTP3086S, an antibody-drug conjugate targeting six-transmembrane epithelial antigen of prostate 1, in metastatic castration-resistant prostate cancer
Abstract: PURPOSE: Six-transmembrane epithelial antigen of the prostate 1 (STEAP1) is highly expressed in prostate cancers. DSTP3086S is a humanized immunoglobulin G1 anti-STEAP1 monoclonal antibody linked to the potent antimitotic agent monomethyl auristatin E. This study evaluated the safety and activity of DSTP3086S in patients with metastatic castration-resistant prostate cancer. METHODS: Patients were enrolled in a 3 + 3 dose escalation study to evaluate DSTP3086S (0.3 to 2.8 mg/kg intravenously) given once every 3 weeks followed by cohort expansion at the recommended phase II dose or weekly (0.8 to 1.0 mg/kg). RESULTS: Seventy-seven patients were given DSTP3086S once every 3 weeks, and seven were treated weekly. Two patients in the once-every-3-weeks dose escalation had dose-limiting grade 3 transaminitis. Grade 3 hyperglycemia and grade 4 hypophosphatemia were dose-limiting toxicities in one patient treated at 1.0 mg/kg weekly. Initial cohort expansion evaluated dosing at 2.8 mg/kg once every 3 weeks (n = 10), but frequent dose reductions led to testing of 2.4 mg/kg (n = 39) in the expansion phase. Common related adverse events (> 20%) across doses (once every 3 weeks) were fatigue, peripheral neuropathy, nausea, constipation, anorexia, diarrhea, and vomiting. DSTP3086S pharmacokinetics were linear. Among 62 patients who received > 2 mg/kg DSTP3086S once every 3 weeks, 11 (18%) demonstrated a ≥ 50% decline in prostate-specific antigen; two (6%) of 36 with measurable disease at baseline achieved a radiographic partial response; and of 27 patients with informative unfavorable baseline circulating tumor cells ≥ 5/7.5 mL of blood, 16 (59%) showed conversions to favorable circulating tumor cells < 5. No prostate-specific antigen or RECIST responses were seen with weekly dosing. CONCLUSION: 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.
Journal Title: Journal of Clinical Oncology
Volume: 37
Issue: 36
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2019-12-20
Start Page: 3518
End Page: 3527
Language: English
DOI: 10.1200/jco.19.00646
PUBMED: 31689155
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Howard Scher
    941 Scher
  2. Daniel C Danila
    99 Danila