AB Science SA communicated the results from phase 3 study evaluating masitinib in prostate cancer during the webcast that was held on May 25, 2021. Masitinib is positioned in combination with docetaxel as first-line treatment of metastatic Castrate Refractory Prostate Cancer (mCRPC) eligible to chemotherapy. Metastatic prostate cancer is still an unmet medical need. The median survival of patients with metastatic prostate cancer is around 2 years and the 5-years survival rate is 30% and there is no drug registered in combination with docetaxel. Masitinib is a tyrosine kinase inhibitor designed to selectively target mast cells (MCs) and macrophages. Innate immune cells, in particular MCs and macrophages, are critical components of the tumor microenvironment, promoting angiogenesis and tumor growth, and also contributing to tumorigenesis by suppression of the immune response: The amount of MCs infiltration into human prostate cancer correlates with prognosis, with lower number of MCs in biopsy specimen leading to better prognosis. There is a positive correlation between MCs infiltrated and tumor microvessel density, indicating a stimulating role of MCs in tumourigenesis. MCs are essential for the outgrowth of early-stage tumors, but not essential at a later stage. MCs increase prostate cancer chemotherapy resistance via modulation of p38/p53/p21 signaling. Prostate cancer bone metastases strongly expressed c-kit. M2 macrophages promote prostate cancer progression and M1 macrophages may also be associated with poor prognosis. The development program in prostate cancer is comprised of AB07004 phase 1/2 proof of concept study (n=34 pts), which supported the combination of masitinib with docetaxel in mCRPC, and AB12003 phase 3 study also in mCRPC patients. Study AB12003 was an international (16 countries), multicenter (67 sites), randomized, double blind, placebo-controlled, 2-parallel group, phase 3 study in mCRPC patients eligible to chemotherapy. The study aimed to compare the efficacy and safety of masitinib (6.0 mg/kg/day) in combination with docetaxel versus placebo in combination with docetaxel. Docetaxel was combined with prednisone, up to ten cycles. The primary endpoint was a composite PFS measured with PCWG2 definition, which is based on the earliest event between radiographic progression, PSA progression, Pain progression, or death. The study pre-specified the overall population and a targeted subgroup defined as patients with Alkaline Phosphatase (ALP) below 250 IU/mL at baseline. ALP below 250 IU/mL is a biologic biomarker that was pre-defined to identify patients with lower extent of (bone) metastases and most likely to respond to masitinib. The study tested the success of the primary endpoint PFS in these two populations as primary analysis with control of alpha risk test for final analysis set at 3.9% in the targeted subgroup and 3.99% in the overall population with a fall back scheme and taken into consideration interim analysis with a peto function. The primary analysis was based on mITT population, which included 450 patients in the targeted subgroup and 712 patients in the overall population. The mITT population exluded 2 patients from ITT population who did not receive the study drug.