Date: 2014-04-07
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting
Company: Bind Therapeutics (USA - MA)
Product: BIND-014 (docetaxel encapsulated in a polymeric nanoparticle)
Action
mechanism: taxane derivative. BIND-014 is a targeted biodegradable polymeric nanoparticle containing the cytotoxic agent docetaxel. BIND-014 is targeted to prostate-specific membrane antigen (PSMA), a cell surface antigen abundantly expressed on the surface of cancer cells and on new blood vessels that feed a wide array of solid tumors. In preclinical cancer models, BIND-014 was shown to deliver up to 20 times more docetaxel to tumors than an equivalent dose of Taxotere. The increased accumulation of docetaxel at the site of disease translated to marked improvements in antitumor activity and tolerability.The development of BIND-014 was funded in part by the National Cancer Institute and the U.S. National Institutes of Standards and Technology (NIST) under its Advanced Technology Program (ATP).
Disease: metastatic cancer, solid tumors
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: The Phase 1 study has an ascending, intravenous dose design to assess the safety, tolerability and pharmacokinetics of BIND-014 in approximately 30 cancer patients. The primary objective of the study is to determine the maximum tolerated dose of BIND-014 and to assess preliminary evidence of antitumor activity. This clinical study is being conducted at the Virginia G. Piper Cancer Center at Scottsdale Healthcare in Scottsdale, Arizona, in collaboration with the Translational Genomics Research Institute and the Scottsdale Healthcare Research Institute, the Karmanos Cancer Institute in Detroit, Michigan, and Marin Specialty Care in Greenbrae, California. (NCT01300533 )
Latest
news: * On April 7, 2014, Bind Therapeutics announced that clinical data on its lead drug candidate, BIND-014, were presented at the American Association of Cancer Research (AACR) meeting. The clinical data from a completed Phase 1 study demonstrate differentiating attributes of BIND-014 administered with a weekly dosing schedule which may enable increased dose intensity and enhanced therapeutic efficacy of BIND-014. In addition, data supporting the potential utility of PSMA as a target and marker for BIND-014 patient selection were presented. In a poster presentation entitled, "A phase 1 study of BIND-014, a PSMA-targeted nanoparticle containing docetaxel, administered to patients with refractory solid tumors on a weekly schedule," Bind Therapeutics researchers presented Phase 1 data on safety, pharmacokinetics and preliminary efficacy of BIND-014 administered as a 60-minute infusion, once weekly for three weeks (Q1W), followed by one week of no treatment over a four-week cycle. Greater dose intensity by approximately 50% was shown with Q1W dosing of BIND-014 as compared to once every three week dosing of BIND-014 described in a previous study. * On April 9, 2013, Bind Therapeutics announced that Phase 1 clinical data for BIND-014 were presented in an oral presentation at the American Association for Cancer Research (AACR) 2013 Annual Meeting. Clinical investigators presented the Phase 1 results with BIND-014 in 28 heavily-pretreated patients with advanced or metastatic solid tumors. In the study, BIND-014 was shown to be generally safe and well-tolerated at the established maximum tolerated dose of 60 mg/m2 and showed encouraging signs of anti-tumor activity including one complete response, three partial responses and five patients with stable disease lasting at least four cycles (> 12 weeks). In addition, the pharmacokinetic (PK) profile of BIND-014 was substantially different from the published PK of conventional docetaxel. In an oral presentation entitled "A Phase 1 Study of BIND-014, a PSMA-targeted Nanoparticle Containing Docetaxel, in Patients with Refractory Solid Tumors," Dr. Von Hoff presented complete Phase 1 clinical data of BIND-014 consistent with previously reported preliminary observations in which safety, tolerability and efficacy in multiple tumor types was demonstrated. BIND-014 was generally safe and well-tolerated with transient and manageable neutropenia as the dose limiting toxicity. Minimal neuropathy, mucositis, fluid retention, rash, and nail changes were observed. The trial also established the maximum tolerated dose of 60 mg/m2 when administering BIND-014 on a once every 3 week (Q3W ) schedule. Evidence of anti-tumor activity was shown with BIND-014 at 60mg/m2 in nine out of the 28 patients treated, ranging from one complete response (cervical cancer), three partial responses (non-small cell lung cancer, prostate and ampullary) and five patients with stabilization of disease lasting at least four cycles (> 12 weeks; pancreatic, colorectal, gall bladder, tonsillar and anal cancer). * On April 4, 2012, Bind Biosciences announced the presentation of late-breaker clinical data for BIND-014 at the American Association for Cancer Research (AACR) 2012 Annual Meeting. Bind presented data from the ongoing Phase 1 clinical study of BIND-014, its targeted docetaxel Accurin, in patients with solid tumors that strongly translated from preclinical data, demonstrated safety and tolerability, and showed evidence of anti-tumor activity with six of 17 patients with advanced or metastatic solid tumor cancers. The preliminary Phase 1 data demonstrated partial response or stable disease in this heavily pretreated patient population with durable responses of up to six months in some cases. In addition, BIND-014 demonstrated evidence of anti-tumor activity in tumors for which conventional docetaxel is known to have minimal activity. In a late-breaking poster presentation entitled “A Phase 1, Open Label, Safety, Pharmacokinetic and Pharmacodynamic Dose Escalation Study of BIND-014 Given by IV Infusion to Patients with Advanced or Metastatic Cancer,” BIND presented clinical data consistent with preclinical observations in which drug concentration at the tumor site and efficacy in multiple tumor types was demonstrated: Preliminary evidence of anti-tumor activity during dose escalation with evidence of anti-tumor activity in six of the 17 patients treated ranging from one durable confirmed partial response (cervical cancer) and five with stabilization of disease (pancreatic, colorectal, bile duct, tonsillar and anal cancer). * On January 7, 2011, Bind Biosciences announced that it has initiated a Phase 1 clinical trial to assess the safety, tolerability and pharmacokinetic profile of BIND-014 in cancer patients. The Phase 1 study has an ascending, intravenous dose design to assess the safety, tolerability and pharmacokinetics of BIND-014 in approximately 30 cancer patients. Patients are currently being screened for eligibility in this clinical trial, which is being conducted at the Virginia G. Piper Cancer Center at Scottsdale Healthcare in Scottsdale, Arizona in collaboration with the Translational Genomics Research Institute (TGen) and the Scottsdale Healthcare Research Institute.
Different tolerability profiles were demonstrated with BIND-014 dosed at Q3W and Q1W. The Q1W schedule demonstrated considerably less neutropenia than Q3W BIND-014, a major dose-limiting toxicity for docetaxel, even at the higher dose intensity.
Pharmacokinetics of BIND-014 were consistent with prolonged retention of BIND-014 particles in the vascular compartment and controlled release of docetaxel at the tumor.
In a poster presentation entitled, "Prostate-specific membrane antigen (PSMA) expression as a potential patient selection marker in patients with refractory solid tumors administered BIND-014, a PSMA-targeted nanoparticle containing docetaxel," Bind Therapeutics researchers presented data from a retrospective analysis which demonstrated PSMA expression in patients responding to treatment with BIND-014 in the phase 1 clinical study.
The PK profile of BIND-014, characterized by prolonged and elevated encapsulated docetaxel levels, was highly differentiated from published PK of conventional docetaxel.
BIND-014 employs a combination of a targeted biodegradable nanoparticle and docetaxel, a proven cancer drug. The ongoing Phase 1 study has reached a dose of 75 mg/m2 with dose escalation continuing and BIND-014 continues to be well-tolerated in the study.
Evidence of antitumor activity in cancers in which conventional docetaxel has minimal activity.
At all dose levels studied, with 75 mg/m2 reached to date, BIND-014 was generally well-tolerated with no new toxicities observed. Dose escalation continues.
Strong translation of pharmacokinetic data from preclinical findings to Phase 1 clinical data with highly differentiated PK profile from conventional docetaxel and strong dose linearity across doses. The clinical results are consistent with the preclinical findings that BIND-014 concentrates drug activity in the tumor resulting in improved efficacy.
