Early-Phase Study of Antibody-Drug Conjugate in Castration-Resistant Prostate Cancer
Posted: Monday, January 20, 2020
According to early-stage research findings published in the Journal of Clinical Oncology, DSTP3086S, a antibody-drug conjugate that targets six-transmembrane epithelial antigen of prostate 1 (STEAP1), may result in a clinical benefit for patients with metastatic castration-resistant prostate cancer. With an acceptable safety profile and evidence of antitumor activity, this agent requires optimization for further clinical development.
“Targeting STEAP1-expressing [metastatic castration-resistant prostate] tumors with an [antibody-drug conjugate] is feasible,” concluded Daniel C. Danila, MD, of Memorial Sloan Kettering Cancer Center, and colleagues.
The phase I, 3 + 3 dose-escalation study included 84 patients, 77 of whom received 0.3 to 2.8 mg/kg of intravenous DSTP3086S every 3 weeks and 7 of whom received 0.8 to 1.0 mg/kg of intravenous DSTP3086S each week. Clinical activity was noted, including a reduction of at least 50% in prostate-specific antigen for 11 of the 62 patients (18%) who received more than 2 mg/kg of DSTP3086S every 3 weeks. Among the 36 patients with measurable baseline disease, 2 (6%) achieved a partial response, and 16 of the 27 patients (59%) with unfavorable baseline levels of circulating tumor cells experienced a conversion to favorable levels of circulating tumor cells. The group undergoing weekly treatment did not experience responses as determined by prostate-specific antigen or Response Evaluation Criteria in Solid Tumors criteria.
Dose-limiting toxicities were experienced in both treatment groups, including grade 3 transaminitis in two patients receiving treatment every 3 weeks and grade 3 hyperglycemia and grade 4 hypophosphatemia in one patient undergoing weekly treatment. Adverse events occurring in more than 20% of overall patients included fatigue, peripheral neuropathy, and gastrointestinal issues. Via initial expansion during dose escalation, 10 patients received 2.8 mg/kg every 3 weeks, but a dose reduction to 2.4 mg/kg (n = 39) occurred following frequent dose reductions.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
