Phase 1 study of PSMA-targeted docetaxel-containing nanoparticle BIND-014 in patients with advanced solid tumors
Mené sur 55 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I évalue la dose maximale tolérée et l'activité antitumorale d'un traitement appelé BIND-014 à base de nanoparticules ciblant PSMA et contenant du docétaxel
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.