Plexxikon Announces Promising Preliminary PLX3397 Phase 1 Extension Data in Patients with Pigmented Villonodular Synovitis (PVNS)

  • 79 Percent of Patients Achieved Partial Response; 21 Percent Had Stable Disease with Targeted Therapy PLX3397

Berkeley, CA — May 14, 2014 — Plexxikon, a member of the Daiichi Sankyo Group, announced today promising, proof-of-concept Phase 1 extension clinical data with PLX3397 in pigmented villonodular synovitis (PVNS), a type of rare, often locally aggressive, musculoskeletal neoplasm that arises from the soft tissues of joints and tendons. Interim data from this ongoing trial show that all evaluable patients treated with PLX3397 achieved either partial responses or stable disease. PLX3397 is a novel, oral small molecule that potently and selectively inhibits CSF1R, KIT and oncogenic FLT3 kinases, which play important roles in cancer. CSF1R, in particular, has been shown to be a primary driver in PVNS. These data are being released today as part of the American Society of Clinical Oncology (ASCO) 50th Annual Meeting Press Program. More detailed data will be presented at the ASCO 50th Annual Meeting, being held May 31-June 3 in Chicago.

The data come from an extension cohort of a multicenter Phase 1 clinical study in solid tumors that enrolled 23 advanced PVNS patients who received at least one dose at the time of the interim analysis. Of the 14 patients with evaluable MRI scans, 11 patients (79 percent) achieved partial response and three patients (21 percent) had stable disease as assessed by a novel scoring method to measure PVNS tumor volume. Mean tumor size reduction was 61 percent. For the 23 enrolled patients, the most common treatment-related side effects were hair color changes, fatigue, nausea, swelling around the eyes, abnormal taste, diarrhea, vomiting, and decreased appetite. Treatment-related, severe adverse events were liver enzyme elevations, hyponatremia, anemia, fatigue, diarrhea, and neutropenia.

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, PLX3397 should reverse the accumulation of macrophages and reduce PVNS tumor size. PLX3397 previously has been shown to inhibit CSF1R-dependent CD14+/CD16+ pro-inflammatory monocyte cell numbers in cancer patients.

“These preliminary data suggest that PLX3397 may offer a treatment alternative for PVNS patients, whose options are largely limited to surgical resection which in advanced disease is often not curative and associated with a relative degree of morbidity,” said William D. Tap, MD, principal investigator and Chief of the Sarcoma Medical Oncology Service, at Memorial Sloan Kettering Cancer Center (MSKCC). “Testing PLX3397 in a larger cohort of patients will determine its full clinical profile.”

“By blocking a key component of both the tumor and its micro-environment, PLX3397 offers a novel therapeutic approach for PVNS and other cancer patients,” said Gideon Bollag, PhD, Chief Executive Officer of Plexxikon. “We are strongly encouraged by these clinical results, which show proof of mechanism and suggest that PLX3397 may be useful not only in this rare tumor type, but in other indications with CSF1R-driven tumors. PLX3397 is a key component of Plexxikon’s broad pipeline of targeted therapy.”

PLX3397 received Orphan Drug designation by the FDA in February 2014 for the treatment of PVNS and giant cell tumor of tendon sheath.

Plexxikon and Daiichi Sankyo plan to initiate a Phase 3 clinical trial in PVNS patients.

Phase 1 PVNS Extension Cohort Study Design
Twenty-three patients with advanced PVNS were treated with PLX3397 1000 mg total oral daily dose for 28-day cycles. An MRI assessment of tumor volume by a central musculoskeletal radiologist blinded to chronology was performed every two cycles using a novel Tumor Volume Score developed specifically for PVNS. Complete response was defined as 100 percent decrease; partial response was ≥ 50 percent to 99 percent decrease; progressive disease was ≥ 30 percent increase relative to lowest score; and all else was stable disease. Patients remained on treatment until disease progression or intolerability.

PLX3397 Data Presentation at ASCO – Abstract #10503
Dr. Tap will be presenting this abstract in an oral presentation, “A pilot study of PLX3397, a selective colony-stimulating factor 1 receptor (CSF1R) kinase inhibitor, in pigmented villonodular synovitis (PVNS),” at the American Society of Clinical Oncology (ASCO) 50th Annual Meeting, at 9:00 AM CT on June 1, 2014, in Chicago.

About PLX3397
PLX3397 is a novel, oral small molecule that potently and selectively inhibits CSF1R, KIT, and oncogenic FLT3 kinases. CSF1R and KIT regulate key components of both the tumor and its microenvironment (macrophages, osteoclasts, mast cells).

In addition to the Phase 1 PVNS extension cohort, PLX3397 is being evaluated in several other clinical indications, including glioblastoma, melanoma, acute myelogenous leukemia, and breast cancer. For more information on PLX3397 clinical trials, please visit

About PVNS
PVNS is a rare proliferative neoplastic tumor that affects the synovium and tendon sheaths in young and middle-aged adults of both sexes. Patients are commonly diagnosed in their 20s to 50s and can experience severe debility as a result of local growth of tumor within or around a joint. Diffuse PVNS is an aggressive form of the disease, and can affect the entire lubricating membrane of either small or large joints, most commonly the knee. Surgical resection and/or local radiation are the standards of care, and there are no drugs currently approved to treat the condition. The diffuse form has an average annual incidence of 1.8 cases per million, and recurrence following surgery is common.

About Plexxikon
Plexxikon, a member of the Daiichi Sankyo Group since April 2011, is a leader in the structure-guided discovery and development of novel small molecule pharmaceuticals to treat human disease. The company’s drug Zelboraf®, (vemurafenib/PLX4032) was approved by the FDA in 2011, and is being co-promoted in the U.S. by Daiichi Sankyo Inc. and Genentech. Plexxikon is developing a portfolio of preclinical and clinical stage compounds to address significant unmet medical needs in oncology and other therapeutic areas. Plexxikon’s Scaffold-Based Drug DiscoveryTM platform integrates multiple state-of-the-art technologies, including structural screening as a key component that provides a significant advantage over other drug discovery approaches.

Paul Lin, MD, MBA
Plexxikon Inc.
+1 (510) 647-4063

For Plexxikon:
Susan Kinkead
+1 (415) 751-3611


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