On October 21, 2016 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that it will discontinue additional enrollment of the phase 3 ENLIVEN study of the investigational oral CSF-1R inhibitor pexidartinib (PLX3397) in tenosynovial giant cell tumor; however, the study will proceed with currently enrolled patients under a revised protocol (Press release, Daiichi Sankyo, OCT 21, 2016, View Source [SID1234515940]). Schedule your 30 min Free 1stOncology Demo!
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Following review of two recently reported cases of non-fatal, serious liver toxicity, the ENLIVEN data monitoring committee (DMC) recommended that further enrollment into the study be suspended. At the time of enrollment suspension 121 patients had been randomized, five patients short of the 126 planned for full enrollment. The DMC also recommended measures to address these safety concerns while maintaining the blinded nature of the study. As a result, ENLIVEN will continue in order to evaluate its efficacy and safety endpoints.
All regulatory authorities involved in the ENLIVEN study have been notified. All patients currently enrolled in ENLIVEN are being informed about this updated safety information and will be offered the opportunity to re-consent for continued participation in the study.
"Ensuring patient safety is our first obligation and we sincerely thank all of the investigators and patients participating in this study," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "Upon completion of the study with currently enrolled patients, Daiichi Sankyo will conduct and report a thorough evaluation of the results and consider any and all appropriate next steps."
ENLIVEN is an ongoing global, multi-center, pivotal two-part phase 3 study evaluating pexidartinib in patients with symptomatic tenosynovial giant cell tumor (TGCT) for whom surgical removal of the tumor would be associated with potentially worsening functional limitation or severe morbidity. The first part of the study, which is the double-blind phase, is designed to evaluate the efficacy and safety of pexidartinib versus placebo. The second part of the study is a longer-term open-label study of pexidartinib.
About TGCT
Tenosynovial giant cell tumor (TGCT) – also known as pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCT-TS) – is a rare, usually non-cancerous tumor that affects the synovium-lined joints, bursae, and tendon sheaths, resulting in swelling, pain, stiffness and reduced mobility in the affected joint or limb.1 It is estimated that TGCT has an annual incidence of 11 cases per million.2 Patients are commonly diagnosed in their 20s to 50s,and depending on the type of TGCT, women can be up to twice as likely to develop a tumor as men.3,4
Primary treatment of TGCT includes surgery to remove the tumor, but in patients with a diffuse form where it can wrap around bone, tendons, ligaments and other parts of the joint, the tumor is more difficult to remove and may require multiple surgeries or joint replacement, eventually advancing to the point where surgery is no longer an option and amputation may be considered. It is estimated that the rate of recurrence can be about 15 to 45 percent.5
About Pexidartinib
Pexidartinib is an investigational novel, oral small molecule that potently and selectively inhibits CSF-1R (colony stimulating factor-1 receptor), which is a primary growth driver of abnormal cells in the synovium that cause TGCT.
Pexidartinib has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of TGCT. Pexidartinib has also been granted Orphan Drug Designation by the FDA for the treatment of PVNS/GCT-TS and received Orphan Designation from the European Commission for the treatment of TGCT. Pexidartinib has not been approved by any regulatory authority for any use.
Pexidartinib is being evaluated in several additional potential clinical indications, including glioblastoma, ovarian, breast, colorectal, pancreatic and prostate cancer, malignant peripheral nerve sheath tumor, and pediatric cancers. It is also being investigated in combination with anti-PD-1 immunotherapy, pembrolizumab, for advanced melanoma or other solid tumors.