A Phase 1 Study Of Bind-014, A Psma-Targeted Nanoparticle Containing Docetaxel, Administered To Patients With Refractory Solid Tumors On A Weekly Schedule

Background: BIND-014 is a novel, targeted, polymeric nanoparticle (NP) containing docetaxel (DTXL). BIND-014 is targeted to prostate-specific membrane antigen (PSMA), a tumor antigen expressed on prostate cancer cells and on the neovasculature of many non-prostate solid tumors. In a previous phase 1 study, the maximum tolerated dose (MTD) of BIND-014 administered on a once every 21 day schedule was determined to be 60 mg/m2. This phase 1 study was designed to evaluate the safety, tolerability, MTD, and pharmacokinetics (PK) of BIND-014 administered weekly. Methods: Patients (pts) with advanced solid tumors, adequate organ function and ECOG 0-1 were enrolled. BIND-014 was administered on days 1, 8, and 15 of a 28 day cycle (Q1W). Dose escalation occurred using a standard 3x3 design with doses ranging between 15-45 mg/m2. Results: Twenty-eight pts were enrolled, 27 were evaluable for toxicity and efficacy. Demographics: 15M/12F; median age 65 yrs (range 38 to 78). Prior lines of cytotoxic chemotherapy for advanced/metastatic disease: median 2 (range 0 to 5). Tumor types: hepatobiliary (HB, 7); non-small cell lung (NSCLC, 3); uterine (2); bladder (2); and other solid tumors (13). BIND-014 demonstrates dose-linear PK that is differentiated from docetaxel and characterized by prolonged circulation. Dose limiting toxicities of gr 3 mucositis in 1 pt and febrile neutropenia in 1 pt occurred at 45 mg/m2; MTD on this schedule and in this patient population was determined to be 40 mg/m2. The most common (>10% pts) treatment related AEs included gr 1-4 neutropenia, gr 1-2 alopecia, gr 1-3 anemia, gr 1-2 diarrhea, gr 1-2 dry mouth, gr 1-3 fatigue, gr 1-2 leukopenia, gr 1-3 mucositis and gr 1-2 nausea. All observed toxicities were docetaxel-associated, and several common docetaxel toxicities were mild or absent including nail changes, sensory neuropathy, epistaxis and hyperlacrimation. Confirmed partial responses were observed in 2 pts (breast and gastroesophageal). Stable disease lasting ≥ 12 weeks was observed in 4 pts, including NSCLC, cholangiocarcinoma, ampulla of vater, and pancreatic cancers. Conclusions: Weekly BIND-014 was tolerable with predictable, manageable toxicities and reversible myelosuppression. The MTD on the Q1W schedule was 40 mg/m2. This dose translates to a 50% increase in dose exposure per 28-day schedule as compared to the once every 21 day schedule. Activity is noted in multiple tumors including breast and gastroesophageal cancer. Final phase 1 data will be presented. Phase 2 trials with weekly BIND-014 have been initiated. Citation Format: Monica Mita, Howard Burris, Patricia LoRusso, Lowell Hart, Peter Eisenberg, Alain Mita, Susan Low, Jason Summa, Gregory Berk, Jasgit Sachdev. A phase 1 study of BIND-014, a PSMA-targeted nanoparticle containing docetaxel, administered to patients with refractory solid tumors on a weekly schedule. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT210. doi:10.1158/1538-7445.AM2014-CT210