CNS Penetration, PK and PD of Preoperative CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma

Exclusion Criteria

• •The presence of any of the following will exclude a subject from enrollment:
• •1. Subject has received anti-cancer therapy (either approved or investigational) within ≤ 4 weeks (6 weeks for nitrosoureas) or 5 half-lives, whichever is shorter, prior to starting CC-90010. If subject received prior immunotherapy (immune checkpoint inhibitor, vaccine, etc.), a 2 week wash-out is required. For a subject treated with the Optune-TTF device, a 2 day period without use is required.
• •2. Toxicities resulting from prior chemotherapy, surgery, or radiotherapy must have resolved to ≤ NCI CTCAE (version 5.0) Grade 1 prior to starting CC-90010 treatment (with the exception of Grade 3 alopecia).
• •3. Subject has undergone major surgery ≤ 4 weeks or minor surgery ≤ 2 weeks prior to starting CC-90010 or subject who has not recovered from surgery.
• •4. Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) ≥ NCI CTCAE Grade 2, despite medical management, or any other significant GI disorder that could affect the absorption of CC-90010.
• •5. Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages.
• •6. Evidence of CNS hemorrhage on baseline MRI or CT scan (except for post-surgical, asymptomatic Grade 1 hemorrhage that has been stable for at least 4 weeks).
• •7. Subject who requires increasing doses of corticosteroids to treat symptomatic cerebral edema within 7 days of study therapy.
• •8. Known symptomatic acute or chronic pancreatitis.
• •9. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• •* LVEF \< 45% as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO).
• •* Complete left bundle branch or bifascicular block.
• •* Congenital long QT syndrome.
• •* Persistent or clinically meaningful ventricular arrhythmias or atrial fibrillation.
• •* QTcF ≥ 480 msec on Screening ECG (mean of triplicate recordings); a marked baseline prolongation of QT/QTc interval, using Fridericia´s QT correction formula.
• •* History of additional risk factors for Torsade de Pointes (TdP) (e.g. heart failure, hypokalemia, family history of Long QT syndrome.
• •* Use of concomitant medications that prolong the QT/QTc interval.
• •* Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting CC-90010.
• •* Other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure ≥ 160/95 mm Hg).
• •10. Pregnant or nursing females.
• •11. Known HIV infection.
• •12. Known chronic active hepatitis B or C virus (HBV, HCV) infection.
• •13. Subject with a requirement for ongoing treatment with therapeutic dosing of anticoagulants or for ongoing prophylactic anticoagulation. Low dose low molecular weight heparin for catheter maintenance is allowed.
• •14. History of concurrent second cancers requiring active, ongoing systemic treatment.
• •15. Evidence of history of bleeding diathesis.
• •16. Subject with known prior episodes of non-arteritic anterior ischemic optic neuropathy (NAION) should be excluded from the study. CC-90010 should be used with caution in subjects with retinitis pigmentosa.
• •17. Subject has any significant medical condition (e.g., active or uncontrolled infection or renal disease), laboratory abnormality, or psychiatric illness that would prevent the subject from participating (or compromise compliance) in the study or would place the subject at unacceptable risk if he/she were to participate in the study.
• •18. Subject has any condition that confounds the ability to interpret data from the study.
• •19. Subject with poor bone marrow reserve as assessed by Investigator such as in the following condition:
• •• Requiring regular hematopoietic support (blood or platelet transfusions, erythropoietin, granulocyte colony stimulating factor \[GCSF\] or other hematopoietic growth factors)
• •20. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to starting study drug.
• •• Acute symptoms must have resolved and based on investigator assessment in consultation with the medical monitor, there are no sequelae that would place the participant at a higher risk of receiving study treatment.
• •21. Previous SARS-CoV-2 vaccine within 14 days of starting drug study.