Date: 2015-11-18
Type of information: Initiation of the trial
phase: 1
Announcement: initiation of the trial
Company: AstraZeneca (UK) Bind Therapeutics (USA - MA)
Product: AZD2811
Action
mechanism: kinase inhibitor/Aurora kinase inhibitor/Accurin. AZD2811, a novel, selective inhibitor of Aurora B kinase that has been shown to be active in both solid and hematological tumors in preclinical models, is the second Accurin candidate to enter clinical development. 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. Tissue targeting is achieved by engineering the physical and chemical properties—size, shape and surface properties—of the Accurin to allow it to escape through gaps in the blood vessels surrounding tumors and other disease sites. Cellular targeting is achieved using proprietary targeting ligands on the surface of the Accurin that binds to specific cell surfaces or tissue markers. Accurins are designed with specific polymers that provide for the controlled and timely release of the therapeutic payload. Upon administration, the therapeutic payload begins to diffuse through the polymeric matrix. Subsequently, the polymer breaks down to lactic acid, a compound naturally found in the body. If the therapeutic payload releases before the Accurins accumulate at the disease site, the Accurins will be unable to effectively increase drug concentration in the diseased tissue and the anticipated therapeutic impact will be minimized or lost. Similarly, if the therapeutic payload is not released, or releases too slowly, the anticipated therapeutic impact will be lost or minimized and new toxicities may be created. By combining prolonged circulation, triple targeting and controlled and timely release of the therapeutic payload, Accurins have the potential to significantly increase the net clinical benefit associated with the therapeutic payload and result in efficacy and safety currently not achievable through other therapeutic modalities.
Disease: advanced solid tumours
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This Phase I study is primarily designed to evaluate the safety and tolerability of AZD2811 at increasing doses in patients with advanced solid tumours and for whom no standard of care exists. The study will be conducted in two parts, a dose-escalation phase (Part A) and a dose expansion phase (Part B). During Part A, the dose-escalation phase, patient enrolment will proceed according to a 3+3 design where the maximum tolerated dose (MTD) or the recommended Phase II dose (RP2D) will be identified. The study will also characterize the pharmacokinetic (PK) profile of AZD2811 and will explore the potential biological activity by assessing anti-tumour activity in patients. Once the MTD is established, Part B (the dose expansion phase) will commence and will enroll patients in 3 groups. Part B will further explore PK parameters, safety, tolerability, and preliminary anti-tumour activity of the AZD2811 RP2D as monotherapy (Group 1) in patients with relapsed/refractory SCLC, and when combined with irinotecan (Group 2 and Group 3). In Part B-Group 2, PK, the safety and tolerability of the AZD2811 will be assessed in a lead-in cohort when given in combination with irinotecan. When a safe and tolerated dose for the AZD2811 and irinotecan combination has been defined, an additional 30 patients will be enrolled to assess efficacy (Part B-Group 3). (NCT02579226 )
Latest
news: * On November 18, 2015, Bind Therapeutics announced that AstraZeneca has initiated patient dosing in a phase 1 clinical trial of the Accurin AZD2811 drug candidate in solid tumors. The phase 1 trial is enrolling patients with advanced solid tumors, including patients with small cell lung cancer, and is being conducted by AstraZeneca under the companies' 2013 collaboration agreement with Bind managing all chemistry, manufacturing and control activities. BIND earned a $4.0 million clinical milestone for dosing of the first patient. The phase 1 clinical trial is designed to evaluate the safety and tolerability of AZD2811 at increasing doses. The first part of the two-part study will evaluate the maximum tolerated dose (MTD) and the recommended phase 2 dose will be identified. The study will also characterize the pharmacokinetic (PK) profile of AZD2811 and will explore the potential biological activity by assessing anti-tumor activity. The second part of the study will begin upon determination of the MTD and will further explore PK parameters, safety, tolerability and preliminary anti-tumor activity of AZD2811. * On June 23, 2015, Bind Therapeutics announced that the FDA has authorized the use of AstraZeneca's Accurin AZD2811 in clinical trials under an investigational new drug (IND) application. BIND is collaborating with AstraZeneca on the development of AZD2811, an Aurora B Kinase inhibitor that has been shown to be active in both solid and hematological tumors in preclinical models, and the companies anticipate enrolling patients in a phase 1 clinical trial with AZD2811 in the fourth quarter of this year. Bind will earn a $4 million milestone payment upon first dosing a patient in a phase 1 clinical trial with AZD2811. Bind and AstraZeneca expect to enroll the first patient in a phase 1 clinical trial with AZD2811 in the fourth quarter of 2015. Under terms of the collaboration, AstraZeneca is responsible for clinical development and commercialization and Bind is responsible for conducting clinical manufacturing through at least the end of phase 2 clinical trials. Preclinical data on AZD2811 were presented at the 2015 American Association of Cancer Research (AACR) annual meeting in April 2015, including data demonstrating promising in vivo and in vitro tumor growth inhibition as monotherapy in models of diffuse large B-cell lymphomas (DLBCL) and small cell lung cancer (SCLC). Additional data showed that AZD2811 delivers prolonged exposure to active drug while having the potential to adapt the dosing regimen, potentially achieving an improved therapeutic index. In addition, using mass spectrometric imaging, AZD2811 was shown to accumulate in tumors and achieve prolonged tumor drug exposure. This represents the first time distribution of nanoparticles in tumors has been demonstrated. Previously, preclinical tumor model data were presented showing that AZD2811 minimizes the bone marrow toxicity seen with the parent compound, which has limited the clinical utility of Aurora B kinase inhibitors as a class.
