A pilot study of PLX3397, a selective colony-stimulating factor 1 receptor (CSF1R) kinase inhibitor, in pigmented villonodular synovitis (PVNS).

Session Type and Session Title: 
Oral Abstract Session, Sarcoma
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 10503^)
William D. Tap, Stephen Patrick Anthony, Bartosz Chmielowski, Arthur P. Staddon, Allen Lee Cohn, Geoffrey Shapiro, Igor Puzanov, Eunice L Kwak, Andrew J Wagner, Charles Peterfy, Henry H Hsu, Carolyn Gee, Paul S. Lin, Sandra Tong, Zev A. Wainberg; Memorial Sloan Kettering Cancer Center, New York, NY; Evergreen Hematology and Oncology/US Oncology Research Affliate, Spokane, WA; University of California, Los Angeles, Los Angeles, CA; University of Pennsylvania School of Medicine, Philadelphia, PA; Rocky Mountain Cancer Center/US Oncology, Denver, CO; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Vanderbilt University, School of Medicine, Nashville, TN; Massachusetts General Hospital, Boston, MA; Spire Sciences, Inc., Boca Raton, FL; Plexxikon Inc., Berkeley, CA; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: PLX3397 is a novel, oral small molecule that potently and selectively inhibits CSF1R, Kit, and Flt3 kinases. CSF1R and Kit regulate key components of both the tumor and its microenvironment (macrophages, osteoclasts, mast cells). PVNS is a rare proliferative neoplasm involving the synovium of joints or tendon sheaths. Tumors contain CSF1R-bearing macrophages recruited by local overexpression of CSF-1 due to a gene translocation. Methods: Patients (pts) with advanced PVNS were enrolled onto an expansion cohort of an ongoing single-arm, multicenter, clinical study. PLX3397 was given orally, 1000 mg daily (600 mg AM, 400 mg PM – 28 day cycles). MRI assessment by a central musculoskeletal radiologist blinded to chronology was performed every 2 cycles using a novel Tumor Volume Score (TVS) developed specifically for PVNS. Partial response (PR) was defined as ≥50% decrease in TVS compared to screening and progressive disease was ≥30% increase relative to lowest score. Patients remained on treatment until disease progression or intolerability. Results: 17 PVNS pts have been enrolled to date. Median exposure 166 days (range 23- 264). 59% pts were women; median age 46 yrs (range 22-80). Tumor locations: knees (12), ankles (2), feet (2), elbow (1). Of the 11 pts with evaluable MRI scans at this interim analysis, 7 pts (64%) achieved a PR and 4 pts (36%) had stable disease (SD). Mean tumor size reduction was 51% (range: -10% to -88%). Clinical improvements were seen in pain, stiffness, and overall function. Common AEs (>10%): fatigue, nausea, hair color changes, and diarrhea. Treatment-related AEs ≥Grade 3: anemia (1), hyponatremia (2), elevated ALT and AST (1), fatigue (1) and diarrhea (1). Conclusions: PLX3397 was well tolerated and demonstrated profound activity as measured by a novel response criterion in pts with advanced PVNS. PLX3397 warrants further study in a larger clinical trial. Clinical trial information: NCT01004861.

Percent change in TVS compared to screening.
Patient Cycle
Best response
3 5 7 9
1 -64% -40% -68% -64% PR
2 -85% -85% -87% -88% PR
3 -50% -50% -50% -58% PR
4 -60% -75% - -83% PR
5 -13% -13% -13% - SD
6 -42% -50% -58% - PR
7 -5% -10% - - SD
8 -40% - - - SD
9 -43% -57% - - PR
10 -50% - - - PR
11 -39% - - - SD