Daiichi Sankyo Europe and Plexxikon Inc., a member of the Daiichi Sankyo Group, announced today that The New England Journal of Medicine (NEJM) published clinical trial results demonstrating that the investigational drug, PLX3397, an oral targeted CSF-1R inhibitor, induced prolonged tumor regressions in most patients with tenosynovial giant cell tumor (TGCT), a rare, locally aggressive neoplasm of the joint or tendon sheath.
Following phase 1 dose-escalation, which evaluated the safety and pharmacokinetics of PLX3397 in solid tumors, 23 patients with advanced TGCT were dosed in a single-arm, multi-center, extension cohort to evaluate the safety and efficacy of PLX3397 at 1,000 mg/day. In an intention-to-treat analysis of response by RECIST 1.1 criteria, 12 out of 23 patients achieved a partial response with PLX3397 for an overall response rate of 52 percent [95 percent CI: 32 - 73 percent], and an additional seven patients had stable disease, providing a disease control rate of 83 percent [95 percent CI: 67 - 98 percent]. Responses to PLX3397 usually occurred within four months of treatment and the median duration of response exceeded eight months. Median progression-free survival has not yet been reached in this study.
"TGCT can be a very difficult disease to manage, with treatment options largely limited to surgery to remove as much of the tumor as possible. Despite the best surgical intervention, recurrence of diffuse TGCT is high and the disease may advance to the point where surgery is no longer an option," said William D. Tap, MD, lead author of the study and Chief of the Sarcoma Medical Oncology Service at Memorial Sloan Kettering Cancer Center. "These preliminary results demonstrate that by targeting CSF-1R, PLX3397 may inhibit tumor growth in some patients with TGCT, potentially offering those patients an alternative non-surgical treatment option."
"The patient responses highlighted in the NEJM publication are very encouraging and underscore our rationale for initiating a global, phase 3 study of PLX3397 in TGCT," said Paul S. Lin, MD, MBA, Chief Operating Officer of Plexxikon. "Our TGCT trial offers important preliminary proof-of-concept on the efficacy of selective CSF-1R inhibition. The targeted molecular design of PLX3397 is another hallmark of our efforts to bring new targeted therapies to patients who need them."