PURPOSE - First-in-human phase 1 trial to determine the safety, pharmacokinetics, and anti-tumor activity of BIND-014, a novel, tumor 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/m2 and 15 to 45 mg/m2, 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 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 to conventional docetaxel. Clinical activity was noted in multiple tumor types. The recommended phase 2 dose of BIND-014 is 60 mg/m2 every three weeks or 40 mg/m2 weekly.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2016 Feb 04 [Epub ahead of print]
Daniel Von Hoff, Monica M Mita, Ramesh K Ramanathan, Glen J Weiss, Alain C Mita, Patricia M LoRusso, Howard A Burris, Lowell L Hart, Susan C Low, Donald M Parsons, Stephen E Zale, Hagop Youssoufian, Jason Summa, Jasgit C Sachdev
Translational Genomic Research Institute and Virginia G. Piper Cancer Center. , Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center. , Hematology-Oncology, Mayo Clinic. , Clinical Research, Cancer Treatment Centers of America. , Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center. , Yale Cancer Center, Yale University. , Sarah Cannon Research Institute, Sarah Cannon Research Institute. , Hematology/Oncology, Florida Cancer Specialists. , R&D, BIND Therapeutics, Inc. , R&D, BIND Therapeutics, Inc. , R&D, BIND Therapeutics, Inc. , R&D, BIND Therapeutics, Inc. , R&D, BIND Therapeutics VGPCC Clinical Trials, TGen Clinical Research Service.