Date: 2016-04-06
Type of information: Results
phase: 2
Announcement: results
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: non-small cell lung cancer (NSCLC)
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: [36.1-68.5] [50.6-85.3] [53.5-83.4] [69.3-96.2] (1 confirmed, 3 unconfirmed) (1 confirmed, 3 unconfirmed) In the squamous histology cohort, data from 20 patients in the intent-to-treat (ITT) population and 11 patients from the Per-Protocol (PP) subset demonstrated an interim 6wDCR of 25 percent (95% CI [confidence interval], 9% to 49%) and 45.5 percent (95% CI, 17% to 77%), respectively. There were no tumor responses by RECIST v1.1. The final median OS in nine patients with squamous histology from the BIND-014-005 trial was 11.1 months, confirming the interim median OS reported previously, with a 1-year survival rate of 44 percent. These data compare favorably with currently approved treatments. As a reference, in the CheckMate 017 trial in 2nd line NSCLC of squamous histology, a median OS of 9.2 months and 6.0 months and 1-year survival rates of 42 percent and 24 percent were reported for Opdivo® (nivolumab) and docetaxel, respectively. In the KRAS mutant cohort, data from 23 patients in ITT population and 14 patients from the PP subset demonstrated an interim 6wDCR of 17.4 percent (95% CI, 5% to 39%) and 28.6 percent (95% CI, 8% to 58%) respectively, which did not meet pre-specified criteria to move to the second stage of the iNSITE 1 trial. The overall response rate (ORR) by RECIST v1.1 was 4 percent (ITT) and 7 percent (PP). Patients currently enrolled in this cohort will continue to be followed for safety and efficacy. Safety data in more than 200 patients treated with BIND-014 to date continue to demonstrate meaningful improvements in hematologic and non-hematologic toxicities when compared to historical docetaxel data. Enrollment is ongoing in the phase 2 iNSITE 2 trial with BIND-014 in patients with advanced cholangiocarcinoma, bladder, cervical and head and neck cancers. Topline data for the second stage of iNSITE 2 are anticipated in the first half of 2016.* On April 6, 2016, Bind Therapeutics announced preliminary top-line results from the BIND-014 (PSMA-targeted docetaxel nanoparticles) phase 2 iNSITE 1 trial in advanced non-small cell lung cancer (NSCLC) of squamous histology. In the iNSITE 1 trial, for the primary endpoint, BIND-014 demonstrated a 52.5 percent 6-week disease control rate (6wDCR) for the intent-to-treat population (n=40) and a 70.0 percent 6wDCR in the per protocol population (n=30), which exceeded the protocol defined criteria for success of 65 percent. Bind intends to seek licensing or collaboration opportunities for further development of BIND-014 in NSCLC. In the first stage of the iNSITE 2 trial, for the primary endpoint, BIND-014 demonstrated an objective response rate of 10 percent in the head and neck cancer cohort (n=20); there were no objective responses in the cervical cancer cohort (n=23). Based on these results, Bind has decided to halt further enrollment in the iNSITE 2 trial in advanced cervical and head and neck cancers. Data from the trial suggest that BIND-014 continues to provide meaningful improvements in safety and tolerability, and at least similar efficacy when administered at a 20 percent lower dose in comparison to historical studies with docetaxel. As a result, the Company believes that these new data further validate the potential of the Accurins® platform.
Binds intends to pursue additional development of BIND-014 through a collaboration or licensing opportunity. This decision follows an analysis of 40 patients in the intent-to-treat (ITT) population and 30 patients in the per-protocol (PP) population with squamous histology NSCLC:
*Per the study protocol, scans were performed every 6 weeks after Cycle 1 Day 1 and had a ± 7 day allowance. The primary endpoint was strictly defined as disease control rate of 6 weeks or greater which had the effect of excluding patients whose data was gathered within the 7 day allowance of the 6 week timepoint. As a result, patients whose first post-treatment scan occurred between week 5 and week 6 were excluded from the primary analysis. Including these patients in a sensitivity analysis results in an 86.7 percent response rate in the PP population. While the study protocol does not permit the inclusion of these patients in the primary endpoint, the Company believes these data are meaningful. ITT [n=40] PP[n=30] 6-week Disease Control Rate
(6wDCR)52.5% 70.0% 6wDCR ± 7 days* 70.0% 86.7% Overall Response Rate (ORR) 10.0% 13.3% Additional details from the iNSITE 1 trial will be presented at an upcoming medical meeting..* On January 27, 2016, Bind Therapeutics announced that the iNSITE 1 trial in non-small cell lung cancer (NSCLC) with squamous histology is fully enrolled and data is expected to be available by the end of the first quarter of 2016. * On December 14, 2015, Bind Therapeutics announced that the squamous histology non-small cell lung cancer (NSCLC) cohort of the phase 2 iNSITE 1 trial will advance to the second stage and complete enrollment to 40 patients. The company also announced that the KRAS mutant NSCLC arm will not advance to the second stage. The rationale for these decisions is based on safety and efficacy data from the planned interim analysis of iNSITE 1 as well as updated overall survival (OS) data in the squamous cohort from the previous clinical trial in the broad NSCLC population, the BIND-014-005 trial. As of October 29, 2015, both the squamous and KRAS cohorts had reached the predefined 20-patient enrollment mark for stage 1, triggering a planned evaluation of the data against pre-specified gating criteria for continuation to stage 2. The major criteria for advancing to the second stage included 6-week disease control rate (6wDCR), tolerability and, in the case of the squamous histology cohort, confirmation of the OS data from the BIND-014-005 trial.
