Basilea plans progression of oncology candidate to targeted, biomarker-driven phase 2 study

Basilea Pharmaceutica Ltd. (SIX: BSLN) announced that it plans to advance the clinical development of its novel tumor checkpoint controller lisavanbulin (BAL101553) by focusing on a targeted, biomarker-driven approach based on the initial results from the two recent phase 1/2 clinical studies.

The phase 1 study (NCT02490800) with daily oral lisavanbulin with recurrent glioblastoma (GBM), or high grade glioma, was completed in August 2019. Basilea has now also completed an interim data review of the ongoing open-label phase 2a expansion study using weekly 48-hour intravenous (i.v.) administration in twelve patients with recurrent GBM and nine patients with platinum-resistant ovarian cancer (NCT02895360).

Glioblastoma is the most common type of primary brain cancer and one of the most lethal types of cancer
Across the two studies, profound objective responses, with more than 80% reduction of the GBM tumor area, were observed in two patients with glioblastoma, who continue to remain on treatment with lisavanbulin. In the ovarian cancer group, four patients showed reduction in target lesion size but did not meet the formal response criteria of the study protocol. The safety profile observed with daily oral or weekly 48-hour i.v. lisavanbulin was consistent with previous studies. Basilea plans to submit the data for presentation at upcoming scientific conferences.

Dr. Marc Engelhardt, Basilea’s Chief Medical Officer, said: “We have observed clinical activity of lisavanbulin in recurrent glioblastoma, with profound clinical responses seen in a subset of patients. Based on this observation, we are investigating a panel of biomarkers, including end-binding protein 1, EB1, which could be useful for identifying cancer patients that may benefit most from the treatment with lisavanbulin. This allows us to take a targeted approach for advancing the clinical development of lisavanbulin, moving from the evaluation of an unselected patient population to a biomarker-driven phase 2 study in recurrent glioblastoma and potentially additional tumor types. Additionally, we currently intend to focus on the oral formulation in the next stage of clinical development of lisavanbulin given the consistent outcome observed with both formulations.”

There will be no additional patients enrolled in the weekly 48-hour i.v. infusion study. All ongoing patients will remain on treatment as long as they continue to benefit from treatment.

EB1 was previously identified by Basilea as a potential response-predictive biomarker for lisavanbulin, based on comprehensive preclinical studies in glioblastoma models. Initial clinical evidence was then provided in August 2019, when Basilea announced the completion of patient enrolment into the phase 1 study with daily oral lisavanbulin in recurrent glioblastoma or high-grade glioma. One glioblastoma patient in that study, whose tumor tissue was strongly positive for EB1, was reported as an exceptional long-lasting responder.

In the U.S., a phase 1 study is being conducted in collaboration with the Adult Brain Tumor Consortium (ABTC), in which oral lisavanbulin is evaluated in combination with radiotherapy in patients with newly diagnosed glioblastoma and a reduced sensitivity to chemotherapy with the standard-of-care drug temozolomide.