Basilea Pharmaceutica reports that it initiated a phase 2a study with its investigational oncology drug BAL101553. The study is designed to further characterise safety and tolerability, and to obtain efficacy data in adult patients with advanced or recurrent solid tumours who have failed standard therapy or for whom no effective standard therapy is available. Tumour types were selected based on clinical observations in the phase 1 study and a detailed analysis of potential patient stratification biomarkers across tumour indications. The study will also continue the extensive biomarker testing initiated in Phase 1, to further evaluate dose and patient populations most likely to respond.

BAL101553 is an intravenous and oral small-molecule microtubule-targeting agent (MTA) with a dual action against human tumours, targeting tumour cells refractory to standard MTAs as well as tumour blood supply. In preclinical studies the investigational drug demonstrated potent anti-cancer activity in a broad panel of treatment-resistant tumour models. Tumour cell proliferation was arrested and tumour cell death was induced through a destabilising effect on microtubules, an intracellular network essential for cell division. In addition, tumour-specific vascular disruption activity was observed in preclinical cancer models. First evidence of clinical antitumour activity has been seen in a recently completed phase 1 study.

Prof. Achim Kaufhold, Basilea's chief medical officer, stated: "Following the promising phase 1 results we have swiftly initiated the phase 2a study at leading cancer institutions. Our study will assess BAL101553's safety and efficacy in different solid tumor types in patients refractory to current therapy to facilitate the selection of tumour indications to be included in future expanded phase 2 trials."

The phase 2a open-label multicentre study is scheduled to enroll 40 patients, randomised either to intravenous BAL101553 at the maximum tolerated dose (MTD) determined in the recently completed phase 1 study, or at half of the MTD to determine the optimal dose. Dose selection was supported by preclinical results from a human cancer model, in which similar tumour exposure was achieved for both doses while the lower dose resulted in higher peak intra-tumoural levels, potentially as a result of a less pronounced effect on the vasculature. Anti-vascular effects will be further evaluated in patients through expanded biomarker and functional imaging assessments.

BAL101553 is a novel intravenous small-molecule anti-cancer drug candidate with the potential for oral administration. The agent directly attacks tumour cells by destabilising microtubules that form an intracellular network essential for cell division. In addition, it disrupts tumour blood vessels. The investigational drug has shown broad in-vitro anti-proliferative activity in a panel of tumour models, including many that are not responsive to standard microtubule-targeting agents, such as taxanes or vinca-alkaloids, as a result of diverse resistance mechanisms. Recently, the maximum tolerated dose was determined in a phase 1 study where first evidence of clinical antitumour activity was observed. In preclinical studies BAL101553 demonstrated good compatibility with targeted therapeutic antibodies such as trastuzumab.BAL101553 is a highly soluble prodrug of Basilea's BAL27862. The injectable dosage form is formulated without potentially harmful solubilizers. In addition, the prodrug is orally bioavailable.