Clinical Trials

Date: 2016-04-21

Type of information: Presentation of results at a congress

phase: preclinical

Announcement: presentation of results at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, in Barcelona, Spain, on November 18-21, 2014.

Company: Basilea Pharmaceutica (Switzerland)

Product: BAL101553

Action mechanism:

• microbutubule inhibitor. BAL101553 is an intravenous and oral microtubule-targeting agent. This highly water-soluble prodrug of the synthetic small molecule BAL27862 allows intravenous and oral administration without solubilizing excipients associated with adverse effects. BAL27862 arrests tumor cell proliferation and induces tumor cell death through a characteristic destabilizing effect on microtubules that is distinct from other anti-cancer agents also directed against the microtubule network. Anti-tumor activity has been demonstrated across a broad panel of solid tumor models, including those resistant against conventional microtubule-targeting drugs such as taxanes or Vinca alkaloids.

Disease: treatment refractory tumors

Therapeutic area: Cancer - Oncology

Country:

Trial details:

Latest news:

• • On April 21, 2016, Basilea Pharmaceutica announced that preclinical data on BAL101553 were presented at the American Association for Cancer Research (AACR) annual meeting. The tumor-checkpoint controller BAL101553 is currently in Phase 1/2a clinical development. At the AACR meeting, preclinical data were presented demonstrating anti-cancer activity of BAL101553 against glioblastoma multiforme. BAL101553 efficiently penetrates the brain in preclinical models and has previously demonstrated anti-cancer activity in treatment-refractory solid tumor models alone and in combination with radiotherapy. The data presented at the AACR were generated by the group of Prof. Jann N. Sarkaria (Mayo Clinic, Rochester) and demonstrate statistically significant single agent activity in a panel of in vivo glioblastoma models after daily, oral administration, including models refractory to temozolomide (TMZ) and radiotherapy, the standard of care for newly diagnosed glioblastoma. Moreover, using a model with reduced sensitivity to both radiotherapy and TMZ, BAL101553 combined with either radiotherapy alone or radiotherapy and TMZ together provided additional benefit, leading to statistically significant prolongation of survival as compared to the standard of care treatment regimens. These data indicate that BAL101553 alone or in combination may provide a survival extension in GBM patients, potentially offering an alternative therapeutic option in this area of high medical need.
• • On November 19, 2014, Basilea Pharmaceutica reports that data on its investigational phase 2a anti-cancer drug candidate BAL101553 will be presented at the 26th EORTC-NCI-AACR Symposium* on "Molecular targets and cancer therapeutics" in Barcelona, Spain, November 18-21, 2014. BAL101553 data alone and in combination with radiotherapy in tumor models resistant to clinically relevant microtubule-targeting agents (MTAs) was generated in collaboration with the group of Prof. Martin Pruschy at the Department of Radiation Oncology, University Hospital Zurich. It shows that intravenously or orally administered BAL101553 in combination with radiotherapy led to profound tumor growth delays as compared to single-agent therapy.
• Intravenously or orally administered BAL101553 reduced tumor growth in a taxane-refractory animal model of human cancer, with daily or weekly oral administration eliciting equivalent anti-tumor responses. Moreover, in a tumor model refractory to taxanes and epothilones and with low response to radiotherapy, the combination of intravenously or orally administered BAL101553 and radiotherapy resulted in almost complete tumor stabilization over a prolonged period. Similar effects of BAL101553 were also observed in a second treatment-refractory model alone and in combination with radiotherapy.
• In addition, BAL27862, the active moiety of the water-soluble prodrug BAL101553, was tested in-vitro for anti-cancer effects in human cancer lines resistant to clinically relevant MTAs. BAL27862 reduced cell proliferation when given alone. The effect was further enhanced in combination with ionizing radiation.
• Dr. Laurenz Kellenberger, Chief Scientific Officer of Basilea, said: "Basilea is addressing therapeutic challenges in oncology and infectious diseases by focusing on overcoming resistance to standard treatment regimens and on personalized medicine. BAL101553 showed a profound anti-tumor effect in treatment-refractory models of human cancer after intravenous and oral administration in combination with radiotherapy. This further supports the compound\'s differentiated profile and its potential to treat patients with limited treatment options."
• Presentation on BAL101553 at EORTC-NCI-AACR Symposium 2014: The novel microtubule-destabilizing drug BAL101553 (prodrug of BAL27862) sensitizes a treatment refractory tumor model to ionizing radiation. A. Broggini-Tenzer, F. Bachmann, V. Vuong, A. Messikommer, K. Nytko-Karouzakis, T. O\'Reilly, H. A. Lane, M. N. Pruschy.

Is general: Yes