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

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

Author information

1
Translational Genomic Research Institute and Virginia G. Piper Cancer Center, Scottsdale, Arizona.
2
Cedars-Sinai Medical Center, Los Angeles, California.
3
Mayo Clinic, Rochester, Minnesota.
4
Cancer Treatment Centers of America, Goodyear, Arizona.
5
Yale University, New Haven, Connecticut.
6
Sarah Cannon Research Institute, Nashville, Tennessee.
7
Florida Cancer Specialists, Fort Myers, Florida.
8
BIND Therapeutics, Inc., Cambridge, Massachusetts.
9
BIND Therapeutics, Inc., Cambridge, Massachusetts. jsumma@bindtherapeutics.com.

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.

PMID:
26847057
DOI:
10.1158/1078-0432.CCR-15-2548
[Indexed for MEDLINE]
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