Masitinib in combination with docetaxel helps to prolong progression-free survival in metastatic castrate-resistant prostate cancer eligible to chemotherapy compared to placebo in combination with docetaxel, meeting the primary end point of the phase 3 AB12003 study.
Masitinib in combination with docetaxel helps to prolong progression-free survival (PFS) in metastatic castrate-resistant prostate cancer (mCRPC) eligible to chemotherapy compared to placebo in combination with docetaxel (Docefrez), meeting the primary end point of the phase 3 AB12003 study according to a press release by AB Science.1
Masitinib is an oral tyrosine kinase inhibitor (TKI) that targets macrophages and mast cells. This targeting is important for immunity as it helps to inhibit a limited number of kinases. Masitinib can be developed for a large number of oncologic conditions, including inflammatory disease, and certain central nervous system disease. It can be used in combination with chemotherapy or as a monotherapy. If approved for use in prostate cancer, it will target disease in 125,000 patients.2
The international, multicenter, randomized, double-blind, placebo-controlled, 2-parallel group, phase 3 AB12003 study (NCT03761225) enrolled 580 participants. The secondary end point of the study was overall survival.
The study was broken up into 2 arms. In arm 1, patients received 6mg of masitinib twice a day plus 75mg/m2 of docetaxel once every 3 weeks for 6 cycles. Patients also received prednisone in accordance with usual practice. In arm 2, patients followed the same regiment except that participants received a placebo in place of masitinib.
In order to participate, patients must have had histologically or cytologically confirmed mCRPC and have either been pre-treated with abiraterone with documented disease progression or indicated for initiating docetaxel treatment. Additionally, patients must have had evidence of progressive metastatic disease and adequate organ function. Patients who have been previously treated with chemotherapy were not eligible to participate.
The phase trial 3 trial follows positive results of a phase 1/2 trial which included patients with hormone-refractory prostate cancer who progressed after first-line treatment. During this trial, the novel combination achieved a median OS of 18.4 months with a lower bound of the corresponding one-sided 75% CI of 17.8 months. The median OS observed with masitinib plus docetaxel was 14.4 months.3
Masitinib is also being evaluated for efficacy in pancreatic cancer, which is nearly always fatal. The agent is being investigated in non-resectable locally advanced or metastatic prostate cancer. The investigation is being restricted to patients with cancer-related pain.
If approved by regulatory authorities, the TKI has the potential to target mCRPC in 20,000 to 40,000 patients in Europe and The United States.
Aside from mCRPC, use of masitinib in combination with gemcitabine is being explored in a confirmatory phase 3 trial of patients with pancreatic cancer treated in the frontline setting. The study has met its endpoint of OS with an improvement of 1.8 months compared with the placebo plus gemcitabine arm (P =.007) observed in the population with locally advanced tumors. This translates to a 54% reduction in risk of death. The PFS results for masitinib/gemcitabine were similar to the OS results, showing an improvement of 1.8 months compared with the control arm (P =.039). Further, in this population, masitinib was found to have a manageable safety profile.4