Date: 2013-08-19
Type of information: Completion of the trial
phase: 1-2
Announcement: completion of the phase 1
US authorization
Company: to-BBB (The Netherlands)
Product: 2B3-101 (brain targeted doxorubicin liposomes)
Action
mechanism: cytotoxic antibiotic. 2B3-101 is a glutathione pegylated liposomal doxorubicin. to-BBB has developed 2B3-101 by applying the G-Technology to the already marketed pegylated liposomal doxorubicin formulations (Caelyx®/Doxil®), by conjugating glutathione to the tips of the PEG.
Manufacturing of clinical batches of 2B3-101 is contracted to the experienced company TTY Biopharm (Taipei, Taiwan, R.O.C.). to-BBB has shown a therapeutic benefit and predictable safety profile of clinical-scale 2B3-101, by performing a range of translational research studies, such as extended GLP preclinical safety studies (NOTOX), efficacy studies (NKI) and pharmacokinetics (PK) and biodistribution (NOTOX).
Disease: patients with solid tumors and brain metastases or recurrent malignant glioma
Therapeutic area: Cancer - Oncology
Country: The Netherlands, Belgium, France
Trial
details: The trial will be conducted at the NKI-AVL (Dr. Brandsma, Amsterdam), VUmc (Prof. Verheul, Amsterdam) and LUMC (Dr. Gelderblom, Leiden), all located in the Netherlands. The trial will be managed by the clinical research organization, SMS-oncology. The primary endpoint of the trial i safety, tolerability and determination of the maximum tolerated dose (MTD). Secondary endpoints include determination of the pharmacokinetic profile of 2B3-101 as well as a preliminary assessment of efficacy in women with brain metastases of breast cancer.The study will be conducted in 3 stages:
* Stage 1: 2B3-101 single agent dose-escalation phase.Patients will be assigned to a dose level cohort. - The starting dose will be 5 mg/m2, which is equal to 1/10 of the human equivalent dose of the LD10 of 2B3-101 in rats. A "3+3" dose-escalation design will be used. The study will investigate sequential cohorts consisting of 3-6 patients to be enrolled and treated at the applicable dose level. Planned dose levels for subsequent cohorts are 10, 20, 30, mg/m2 and steps of 10 mg/m2 thereafter. There will be no intra-patient dose escalation. Each treatment cycle consists of 21 days. On day 1 of cycle 1, 2B3-101 will be administered IV with a constant infusion rate not greater than 1 mg/min to minimize the risk of infusion reactions.
Once the MTD of 2B3-101 as single agent has been determined, the study will continue to the breast cancer brain metastases and recurrent malignant glioma dose expansion phases.* Stage 2A: Breast cancer brain metastases expansion phase.In the breast cancer brain metastases expansion phase, each treatment cycle also consists of 21 days. On day 1 of cycle 1, 2B3-101 will be administered IV at MTD with a constant infusion rate not greater than 1 mg/min. Blood samples will be taken on day 1, 2, 3, 5, 8 and 11 to assess the PK profile during the first cycle.* Stage 2B: Recurrent malignant glioma expansion phase.In the recurrent malignant glioma expansion phase, each treatment cycle is equally 21 days long. On day 1 of cycle 1, 2B3-101 at MTD will be administered IV with a constant infusion rate not greater than 1 mg/min. Blood samples will be taken on day 1, 2, 3, 5, 8 and 11 to assess the 2B3-101 PK profile during the first cycle.For all stages a patient will stay on treatment until disease progression, unacceptable toxicity, or discontinuation for any other reason.
Latest
news: * On August 19, 2013, to-BBB, the brain drug delivery company, has announced the successful completion of its 2B3-101 Phase I clinical trial in brain cancer patients, safely reaching clinically effective dosages. to-BBB is now ready to proceed to the Phase IIa part of this trial, treating patients with brain metastases from breast cancer, small cell lung cancer and melanomas, as well as patients with primary, malignant brain cancers (recurrent gliomas). With no commercially available treatments for brain metastases of solid tumors and no effective treatment alternatives in recurrent gliomas, 2B3-101 is targeting a high unmet medical need.
This study with 2B3-101 is being performed in close collaboration with eight specialized clinics in the Netherlands, Belgium and France.
to-BBB is currently planning to open an additional study site in the US, specialized in the treatment of patients with brain metastases. to-BBB submitted an IND application (investigational new drug) to the FDA in July and is now delighted to announce the approval of the IND from the FDA. The IND approval opens up opportunities to involve US medical centers in the development of 2B3-101.
* On June 27, 2011, to-BBB, the Dutch brain drug delivery company, has received approval to start treating patients with brain metastases with its lead product 2B3-101 in a Phase I/II clinical trial.
Based on its proprietary G-Technology® (proprietary brain delivery platform), to-BBB is developing its lead compound 2B3-101, braintargeted doxorubicin liposomes. These liposomes are coated with the endogenous antioxidant glutathione at the tips of polyethylene glycol (PEG) to safely enhance the delivery of free drug to the brain. 2B3-101 has shown reduction of brain tumor growth in preclinical proof-of-concept studies at the Netherlands Cancer Institute. Clinical batches of 2B3-101 have been produced by to-BBB’s manufacturing partner TTY Biopharm and pivotal preclinical safety studies were completed in 2010. to-BBB is now ready to start recruitment of a Phase I/IIa trial involving approximately 40 patients.
