Basilea Begins Phase 2a Expansion Trial Testing BAL101553 in Ovarian, Brain Cancers

Basilea Begins Phase 2a Expansion Trial Testing BAL101553 in Ovarian, Brain Cancers

Basilea Pharmaceutica has dosed its first patient in the expansion part of its Phase 1/2 trial (NCT02895360), which continues to explore the safety and effectiveness of BAL101553, an investigational tumor checkpoint controller, for the treatment of glioblastoma and ovarian cancer.

The open-label Phase 2a expansion is designed to include up to 40 patients with either recurrent glioblastoma — the most aggressive form of brain cancer — or ovarian cancer that failed prior platinum-based chemotherapy. The study is being conducted across several centers in Switzerland.

“The start of the Phase 2a expansion study marks a significant milestone towards establishing clinical proof-of-concept for our biomarker-driven development strategy with our novel tumor checkpoint controller BAL101553,” Marc Engelhardt, MD, Basilea’s chief medical officer, said in a press release.

Cells proliferate in a regulated way, using information about their own internal state and the environment to decide whether to proceed with cell division. If a cell is damaged or fails to meet the requisites to move through the next phase of division, the cycle is halted.

This is achieved through a number of checkpoints.

BAL101553 is a small molecule that activates a checkpoint responsible for assessing if the chromosomes are correctly displayed to be segregated into two daughter cells. By activating this checkpoint, the molecule halts cell division and promotes tumor cell death.

In preclinical studies, BAL101553 showed anti-cancer activity against several types of cancer that are often resistant or refractory to conventional approved therapies. The molecule was also able to penetrate the brain, making it a promising approach for brain tumors.

The ongoing, open-label Phase 1/2 trial is testing BAL101553 in patients with advanced solid cancers and glioblastoma, who failed standard therapy for their tumors.

In Phase 1, researchers assessed the safety and early effectiveness of ascending BAL101553 doses — 30, 45, 70 or 90 mg/m2 — in 20 patients. The medicine was given weekly in 48-hour intravenous infusions, in the first three weeks of every 28-day cycle.

Among the 16 patients able to be evaluated for a response, one ovarian cancer patient had achieved a partial tumor reduction, and one with endometrial cancer has stable disease.

Patients receiving the highest dose experienced severe, but reversible, low neutrophil levels, low sodium concentration, and episodes of hallucinations and uncontrolled movement. For those receiving the 70 mg/m2 dose, researchers reported cases of severe low blood pressure.

Based on this, researchers chose the 70 mg/m2 dosing regimen, given in a weekly 48-hour infusion, to be further tested in the expansion phase.

Trial results were recently presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, in Chicago, in a poster, titled “Phase 1/2a study of BAL101553, a novel tumor checkpoint controller (TCC), administered as 48-hour infusion in adult patients with advanced solid tumors.”

“There are only very limited treatment options available for patients with recurrent glioblastoma and for patients with platinum-resistant or platinum-refractory ovarian cancer,” Engelhardt said. “Our decision to explore the potential clinical benefit in these specific patient populations is based on the results from our Phase 1 studies and our comprehensive non-clinical profiling.”

BAL101553 is also being studied in two additional open-label trials, a Phase 1 trial (NCT03250299) for newly diagnosed glioblastoma and a Phase 1/2 trial (NCT02490800) for recurrent glioblastoma.

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