Phase I Study of PSMA-Targeted Docetaxel-Containing Nanoparticle BIND-014 in Patients with Advanced Solid Tumors

Clin Cancer Res. 2016 Jul 1;22(13):3157-63. doi: 10.1158/1078-0432.CCR-15-2548. Epub 2016 Feb 4.

Abstract

Purpose: First-in-human phase I trial to determine the safety, pharmacokinetics, and antitumor activity of BIND-014, a novel, tumor prostate-specific membrane antigen (PSMA)-targeted nanoparticle, containing docetaxel.

Experimental design: Patients with advanced solid tumors received BIND-014 every three weeks (n = 28) or weekly (n = 27), with dose levels ranging from 3.5 to 75 mg/m(2) and 15 to 45 mg/m(2), respectively.

Results: BIND-014 was generally well tolerated, with no unexpected toxicities. The most common drug-related toxicities (>20% of patients) on either schedule included neutropenia, fatigue, anemia, alopecia, and diarrhea. BIND-014 demonstrated a dose-linear pharmacokinetic profile, distinct from docetaxel, with prolonged persistence of docetaxel-encapsulated circulating nanoparticles. Of the 52 patients evaluable for response, one had a complete response (cervical cancer on the every three week schedule) and five had partial responses (ampullary adenocarcinoma, non-small cell lung, and prostate cancers on the every-three-week schedule, and breast and gastroesophageal cancers on the weekly schedule). Responses were noted in both PSMA-detectable and -undetectable tumors.

Conclusions: BIND-014 was generally well tolerated, with predictable and manageable toxicity and a unique pharmacokinetic profile compared with conventional docetaxel. Clinical activity was noted in multiple tumor types. The recommended phase II dose of BIND-014 is 60 mg/m(2) every three weeks or 40 mg/m(2) weekly. Clin Cancer Res; 22(13); 3157-63. ©2016 AACR.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Surface
  • Docetaxel
  • Drug Administration Schedule
  • Drug Carriers / adverse effects
  • Drug Carriers / pharmacokinetics*
  • Drug Carriers / therapeutic use*
  • Female
  • Glutamate Carboxypeptidase II / antagonists & inhibitors*
  • Humans
  • Male
  • Middle Aged
  • Nanoparticles / adverse effects
  • Nanoparticles / therapeutic use*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Taxoids / therapeutic use*

Substances

  • Antigens, Surface
  • Drug Carriers
  • Taxoids
  • Docetaxel
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II