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

• Published in: Clinical cancer research Vol. 22; no. 13; pp. 3157 - 3163
• Main Authors: Von Hoff, Daniel D., Mita, Monica M., Ramanathan, Ramesh K., Weiss, Glen J., Mita, Alain C., LoRusso, Patricia M., Burris, Howard A., Hart, Lowell L., Low, Susan C., Parsons, Donald M., Zale, Stephen E., Summa, Jason M., Youssoufian, Hagop, Sachdev, Jasgit C.
• Format: Journal Article
• Language: English
• Published: United States 01.07.2016
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Surface; 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
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-15-2548

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/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 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/m2 every three weeks or 40 mg/m2 weekly. Clin Cancer Res; 22(13); 3157–63. ©2016 AACR.