Date: 2016-10-21
Type of information: update on patient enrollment
phase: 3
Announcement: update on patient enrollment
Company: Daiichi Sankyo (Japan)
Product: pexidartinib (PLX3397)
Action
mechanism: kinase inhibitor/multikinase inhibitor. 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 (Pigmented Villonodular Synovitis) extension cohort, PLX3397 is being evaluated in several other clinical indications, including glioblastoma, melanoma, acute myelogenous leukemia, and breast cancer. Pexidartinib also is being studied in the I-SPY 2 TRIAL, a collaborative research effort studying the effects of adding specific investigational drugs to standard chemotherapy prior to surgery in women with newly diagnosed, locally advanced breast cancer. Pexidartinib has been granted Breakthrough Therapy Designation by the FDA for the treatment of tenosynovial giant cell tumour. 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 tenosynovial giant cell tumour.
Disease: tenosynovial giant cell tumour
Therapeutic area: Cancer - Oncology
Country: Australia, Canada, Denmark, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, UK, USA
Trial
details: The ENLIVEN study is a Phase 3 clinical study aims to evaluate the effectiveness of an investigational drug PLX3397 in the treatment of tumour of pigmented villonodular synovitis or giant cell tumor of the tendon sheath in subjects, for whom surgical removal of the tumour would cause more harm than good. The main purpose of this study is to gather information about the investigational drug PLX3397, which may help to treat these tumours. The study consists of two parts. In Part 1, eligible study participants will be assigned to receive either PLX3397 or matching placebo for 24 weeks. A number of assessments will be carried out during the course of the study, including physical examinations, blood tests, imaging studies, electrocardiograms, and questionnaires. MRI scans will be used to evaluate the response of the tumour to the treatment which will be independently assessed by central readers blinded to the treatment assignment. Those subjects, whether assigned to PLX3397 or matching placebo, who have completed Part 1 (i.e, complete 24 weeks of dosing and the Week 25 assessments) will be eligible to advance to Part 2, a long-term treatment phase in which all subjects will receive open-label PLX3397. (NCT02371369)
Latest
news: * On October 21, 2016, Daiichi Sankyo announced that it will discontinue additional enrollment of the phase 3 ENLIVEN study of pexidartinib (PLX3397) in tenosynovial giant cell tumor; however, the study will proceed with currently enrolled patients under a revised protocol. 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. 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.
