Phase III trial of PLX 3397 (pexidartinib) for treatment of giant cell tumor of the tendon sheath is suspended on advice of DMC. Daiichi Sankyo + Plexxikon.

Daiichi Sankyo and Plexxikon have stopped a late-stage trial of pexidartinib on the advice of the Data Monitoring Committee. The Phase III ENLIVEN study was designed to test the investigational oral CSF-1R inhibitor pexidartinib (PLX 3397) in patients with a tumor of pigmented villonodular synovitis--or giant cell tumor of the tendon sheath--for whom surgical removal of the tumor would cause more harm than good. The drug was being compared with placebo to assess the percentage of subjects achieving complete or partial response, and the number of patients who achieve a complete response or partial response at week 25.

Following review of two recently reported cases of non-fatal, serious liver toxicity, the ENLIVEN data monitoring committee recommended that enrollment into the study be suspended.

Comment: Villonodular Synovitis (PVNS) a type of rare, often locally aggressive, musculoskeletal neoplasm arises from the soft tissues of joints and tendons. PVNS tumors are known to express high levels of CSF1, which causes proliferation of tumor-associated macrophages, osteoclasts and other CSF1R-dependent cells. By selectively inhibiting CSF1R, PLX 3397 should reverse the accumulation of macrophages and reduce PVNS tumor size. PLX 3397 previously has been shown to inhibit CSF1R-dependent CD14+/CD16+ pro-inflammatory monocyte cell numbers in cancer patients.