Masitinib Plus Docetaxel Improves PFS in Metastatic Castration-Resistant Prostate Cancer

The novel oral TKI masitinib in combination with docetaxel and prednisone resulted in improved progression-free survival compared with docetaxel plus prednisone in patients with metastatic castration-resistant prostate cancer (CRPC), meeting the predefined primary end point of the phase 2b/3 AB12003 trial (NCT03761225).¹

Patents associated with the data from the study are being filed. Once submitted, detailed findings will be shared during a webcast with key opinion leaders, according to the pharmaceutical company AB Science.

Masitinib was developed to target mast cells and macrophages, which are both key players in cell immunity; the drug does this by hindering a small number of kinases. The mechanism of action of the TKI allows for its use in many conditions within the field of oncology, in inflammatory diseases, and in select central nervous system (CNS) diseases.

Because masitinib has an immunotherapy effect, the agent is hypothesized to favorably impact survival when used either alone or in combination with chemotherapy in patients with cancer. Masitinib has showcased activity on mast cells and microglia, which inhibits the activation of the inflammatory process. As such, the drug is able to impact symptoms experienced with select inflammatory and CNS diseases and the deterioration of such diseases.

In the international, multicenter, randomized, double-blind, placebo-controlled, 2-parallel group, phase 3 trial, investigators enrolled chemotherapy-eligible patients with metastatic CRPC.

To be eligible for enrollment, patients had to have histologically or cytologically confirmed metastatic CRPC that was either pretreated with abiraterone acetate (Zytiga) and had documented disease progression or indicated for the initiation of docetaxel treatment.² Patients also had to have evidence of progressive metastatic disease per Prostate Cancer Clinical Trials Working Group 2 recommendations and have acceptable organ function per the study protocol. If patients had previously received chemotherapy, they were excluded.

Those in the investigative arm received masitinib at a dose of 6.0 mg/kg/day twice daily, in combination with docetaxel at 75 mg/m2 once every 3 weeks for 6 cycles, plus prednisone per standard clinical practice. Patients in the control arm were given placebo plus docetaxel and prednisone at the same dosing and schedule.

The primary end point of the trial is PFS, while overall survival (OS) serves as a secondary end point.

Patient enrollment to the trial was given the green light by the FDA in January 2020, after the company’s investigational new drug application was cleared for the agent’s use in patients with metastatic CRPC who were eligible for chemotherapy.³

In June 2018, an interim analysis was conducted by an independent data monitoring committee. Based on the rules for the assessment, the committee recommended to continue the study in a prespecified subgroup of patients who had been identified by a biomarker.

The probability of success of the trial was projected to exceed 80% in this subgroup per the statistical rule of the protocol at the time of the analysis, with the assumption that patients yet to be enrolled at the time would behave like those who had been analyzed. The subgroup was expected to account for about two-thirds of the population.

Previously, the agent was evaluated in a phase 1/2 trial, which evaluated its use in combination with docetaxel in patients with hormone refractory prostate cancer who experienced disease progression following first-line treatment.⁴

Results indicated that the doublet resulted in a median OS of 18.4 months, with a lower bound of the corresponding one-sided 75% CI of 17.8 months. This finding compared favorably with a meta-analysis that showcased an OS of 14.4 months, following the emergence of enzalutamide (Xtandi).

References

1. AB Science today announced that its masitinib phase 2B/3 study (AB12003) in metastatic castration-resistant prostate cancer (mCRPC) met its predefined primary endpoint. News release. AB Science. April 29, 2021. Accessed April 30, 2021. https://bit.ly/2QNDVZQ
2. Masitinib plus docetaxel in metastatic castration-resistant prostate cancer. ClinicalTrials.gov. Updated November 10, 2020. Accessed April 30, 2021. https://clinicaltrials.gov/ct2/show/NCT03761225
3. FDA green-lights US patient enrollment in masitinib phase 3 study following IND clearance in metastatic castration-resistant prostate cancer eligible to chemotherapy. News release. AB Science. August 1, 2020. Accessed April 30, 2021. https://bit.ly/3eDL9aU
4. Masitinib in oncology. AB Science website. Accessed April 30, 2021. https://bit.ly/3u9FMqm