title: Phase I Study of PSMA-Targeted Docetaxel-Containing Nanoparticle BIND-014 in Patients with Advanced Solid Tumors.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Translational Genomic Research Institute and Virginia G. Piper Cancer Center, Scottsdale, Arizona.
authors: Daniel D
authors: DD
authors: Von Hoff
authors: Cedars-Sinai Medical Center, Los Angeles, California.
authors: Monica M
authors: MM
authors: Mita
authors: Mayo Clinic, Rochester, Minnesota.
authors: Ramesh K
authors: RK
authors: Ramanathan
authors: Cancer Treatment Centers of America, Goodyear, Arizona.
authors: Glen J
authors: GJ
authors: Weiss
authors: Cedars-Sinai Medical Center, Los Angeles, California.
authors: Alain C
authors: AC
authors: Mita
authors: Yale University, New Haven, Connecticut.
authors: Patricia M
authors: PM
authors: LoRusso
authors: Sarah Cannon Research Institute, Nashville, Tennessee.
authors: Howard A
authors: HA
authors: Burris
authors: Florida Cancer Specialists, Fort Myers, Florida.
authors: Lowell L
authors: LL
authors: Hart
authors: BIND Therapeutics, Inc., Cambridge, Massachusetts.
authors: Susan C
authors: SC
authors: Low
authors: BIND Therapeutics, Inc., Cambridge, Massachusetts.
authors: Donald M
authors: DM
authors: Parsons
authors: BIND Therapeutics, Inc., Cambridge, Massachusetts.
authors: Stephen E
authors: SE
authors: Zale
authors: BIND Therapeutics, Inc., Cambridge, Massachusetts. jsumma@bindtherapeutics.com.
authors: Jason M
authors: JM
authors: Summa
authors: BIND Therapeutics, Inc., Cambridge, Massachusetts.
authors: Hagop
authors: H
authors: Youssoufian
authors: Translational Genomic Research Institute and Virginia G. Piper Cancer Center, Scottsdale, Arizona.
authors: Jasgit C
authors: JC
authors: Sachdev
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004337:Drug Carriers / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles / Q000009:adverse effects / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000954:Antigens, Surface; D004337:Drug Carriers; D043823:Taxoids; D000077143:Docetaxel; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II