Business Decision

The objective of this study is to evaluate the response of subjects with recurrent glioblastoma to continuous therapy of PLX3397.

Inclusion Criteria:

• Male or female patients ≥18 years old with a life expectancy of at least 8 weeks
• Radiographically proven recurrent (≥ first relapse), intracranial Glioblastoma (GBM)
• For all patients, availability of at least 10 unstained slides (or archival tumor block sufficient to generate at least 10 unstained slides) from any previous GBM surgery
• Previous treatment with external beam radiation and temozolomide chemotherapy
• Before the first dose of PLX3397,adequate recovery from toxicity of prior therapy as follows:

>28 days for cytotoxic therapy >42 days for nitrosoureas >28 days for bevacizumab >7 days for non cytotoxic therapy such as interferon, tamoxifen, thalidomide, cis-retinoic acid, or erlotinib

• Women of child-bearing potential must have a negative pregnancy test within 7 days of initiation of dosing and must agree to use an acceptable method of birth control while on study drug and for 3 months after the last dose. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year. Men of child-bearing potential must also agree to use an acceptable method of birth control while on study drug.
• Karnofsky performance status of ≥60
• Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.0 x 109/L, Hgb >9 g/dL, platelet count ≥50 x 109/L, Aspartate aminotransferase/Alanine aminotransferase (AST/ALT) ≤2.5x Upper Limit of Normal (ULN), creatinine ≤1.5x ULN)
• Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements

Exclusion Criteria:

• Investigational drug use within 28 days of the first dose of PLX3397
• GBM progression within 3 months of previous radiation by Response Assessment in Neuro-Oncology (RANO) criteria
• History of Grade 2 Common Toxicity Criteria for Adverse Events (CTCAE v4) or greater acute intracranial hemorrhage
• Previous failure of bevacizumab or other vascular endothelial growth factor (VEGF) therapy except in a first line setting
• History of malignant glioma with co-deletion of 1p/19q
• A concurrent active cancer that requires non-surgical therapy (e.g. chemotherapy, radiation, adjuvant therapy). Prior history of other cancer is allowed, as long as there was no active disease within the prior 3 years.
• Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel resection that would preclude adequate absorption
• Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
• Women of child-bearing potential who are pregnant or breast feeding
• corrected QT interval (QTc) ≥450 msec at Screening

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.

Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Adverse event data were collected from after the first dose to 28 days after the last dose.

Adverse events that emerge (or worsen) after the first dose of study drug and within 28 days after the last dose.

Study was terminated due to results noted in primary outcome measure 1. The sponsor felt that the PFS 6 goal of 25% (Lamborn, 2008) was unlikely to be met upon further enrollment.