BARCELONA, Spain—BIND Therapeutics Inc., a clinical-stage nanomedicine platform company developing targeted and programmable therapeutics called Accurins, has presented positive results from its ongoing Phase 2 study of BIND-014 in non-small cell lung cancer (NSCLC), demonstrating it has met the primary objective in the once every three weeks (Q3W) arm as measured by overall response rate. The data demonstrate that BIND-014 is well tolerated with clinically meaningful antitumor activity at a lower dose than conventional docetaxel in patients with advanced or metastatic NSCLC.
BIND-014 also demonstrates promising antitumor activity in patients with tumors expressing KRAS mutations (mutated Kirsten ras oncogene homolog). KRAS mutations in NSCLC are generally associated with poor response to currently available drug therapy regimens, including docetaxel. An additional signal was observed in patients with squamous cell carcinomas, a major NSCLC subtype poorly served by existing available therapies.
These data were presented at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain.
“We believe the activity and tolerability of BIND-014 demonstrated in this study suggest meaningful differentiation from the historical docetaxel experience, in both the broader NSCLC patient population and in two important groups of patients with high unmet medical need,” said Dr. Hagop Youssoufian, BIND’s chief medical officer. “Furthermore, as the first product candidate from our Medicinal Nanoengineering platform to enter the clinic, we believe that the increased efficacy and reduced toxicity at a lower dose compared to historical docetaxel experience suggests that Accurins are successful in targeting the therapeutic payload to the tumor. Based on these positive results, we plan to conduct additional global, multicenter Phase 2 studies to confirm and expand the dataset on BIND-014 and to define an expeditious regulatory path for BIND-014.”
“Data from this open-label study suggest the potential for BIND-014 superiority over docetaxel in the treatment of NSCLC patients,” said Dr. Ronald B. Natale, medical director of the Clinical Lung Cancer Program at the Women's Guild Lung Institute and investigator for the Phase 2 trial of BIND-014 in NSCLC. “Furthermore, BIND-014 demonstrated intriguing activity in patients with KRAS-mutated lung cancers, a group of patients who have historically been unresponsive to standard treatment with docetaxel. This initial experience with BIND-014 provides a glimpse into a new way to selectively target NSCLC tumors, an area of cancer with high unmet need.”
BIND plans to initiate global, multicenter Phase 2 studies of BIND-014 in patients with KRAS mutant NSCLC and in patients with NSCLC of squamous histology who have progressed on prior therapy. These studies aim to assess overall survival and additional endpoints to position BIND-014 for subsequent registration studies.
The Q3W dosing arm of the open-label, multicenter, Phase 2 study discussed in Barcelona enrolled 40 patients with advanced metastatic NSCLC who were treated with 60 mg/m2 of BIND-014 on day one of a 21-day cycle· Five patients (13 percent) achieved a partial response with a median duration of response of 5.2 months and median progression-free survival (PFS) of 2.7 months. There was one unconfirmed partial response that was not included in the analysis per RECIST v1.1. Nine patients were enrolled with a confirmed KRAS mutation, and two of those nine experienced an objective response (22 percent); median PFS in patients with KRAS mutant tumors was 2.7 months.
In patients with squamous cell carcinoma there were no confirmed objective responses; however, median PFS in patients with squamous cell carcinoma was 2.8 months. Prolonged (more than four cycles) disease control was also noted in six of nine (66 percent) patients with squamous histology.
Preliminary median overall survival was 6.2 months for all patients treated, 9.6 months in patients with KRAS mutant tumors and 11.1 months in patients with squamous cell carcinoma.
Twenty-one of 40 patients received four or more cycles of therapy, attesting to the tolerability of BIND-014. Consistent with previous results, neutropenia, anemia, neuropathy and alopecia, commonly observed with docetaxel, were significantly reduced with BIND-014.
Based on the promising results of the Q3W arm and the more patient-friendly once every three weeks dosing schedule, combined with the absence of a confirmed partial response in the first 22 patients enrolled on the Q1W schedule, the company will not continue enrollment on the weekly dosing schedule.
BIND-014, a targeted polymeric nanoparticle, represents the first Accurin nanomedicine from BIND’s Medicinal Nanoengineering platform to reach the clinic. BIND-014 targets prostate-specific membrane antigen, a target expressed on prostate cancer cells and the blood vessels of many types of non-prostate solid tumors, and contains docetaxel, a clinically validated and widely used anticancer agent. In preclinical cancer models, BIND-014 was shown to increase accumulation of docetaxel at the site of disease, which translated to marked improvements in antitumor activity and tolerability. In clinical studies conducted to date, BIND-014 has been shown to be generally well-tolerated and displayed antitumor activity at low doses and in tumors where conventional docetaxel has minimal activity.
Accurins are BIND’s targeted and programmable therapeutics, which are designed utilizing BIND’s medicinal nanoengineering platform, with specified physical and chemical characteristics to target specific cells or tissues and concentrate a therapeutic payload at the site of disease to enhance efficacy while minimizing adverse effects on healthy tissues. Accurins are polymeric nanoparticles that incorporate a therapeutic payload and are designed to have prolonged circulation within the bloodstream, enable targeting of the diseased tissue or cells, and provide for the controlled and timely release of the therapeutic payload. BIND has demonstrated in preclinical studies that Accurins can improve tumor growth suppression, achieve higher concentrations of the payload in tumors compared to the payload administered in conventional form, and have pharmacokinetics and tolerability differentiated from their therapeutic payloads.