Dosing has begun in a Phase I clinical study evaluating BAT8008, an antibody-drug conjugate (ADC) that targets Trop2.
Key objectives of the study are to determine the maximum tolerated dose (MTD), recommended Phase II dose (RP2D), and to evaluate the pharmacokinetics and preliminary efficacy in patients with advanced solid tumours.
Trop2 (Trophoblast cell-surface antigens 2), also known as TACSTD2, M1S1, GA733-1, EGP-1, is a member of the tumour associated calcium signal transduction protein (TACSTD) family, which is related to the regulation of intracellular calcium concentration.
Trop2 is not expressed or has low expression levels in normal human tissues while overexpressed in a variety of solid tumours, especially epithelial tumours. High expression levels of Trop2 in tumours is correlated with poor prognosis for patients.
Trop2 is a validated drug target with one approved drug for the treatment of solid tumours and is a target of high interest for new drug discovery.
BAT8008 was developed by using Bio-Thera Solutions’ ADC linker-payload that includes a cleavable but systemically stable linker, a small molecule topoisomerase I inhibitor and high DAR.
The small molecule topoisomerase I inhibitor payload carried by BAT8008 has a strong cell membrane penetration ability. Consequently, when targeted cancer cells are killed, the payload has shown to be released and kill nearby cancer cells, producing a bystander effect, which has the potential to overcome the heterogeneity of the tumour.
BAT8008 has demonstrated high anti-tumour activity, good stability, and safety in both in vitro and in vivo pharmacological studies.