A Multicenter Phase Ib/II Study to Evaluate the Safety, Efficacy and Pharmacokinetics of NBM-BMX in Patients With Metastatic Uveal Melanoma
Novelwise Pharmaceutical Corporation
Summary
This study is being done to find the best dose of an investigational drug called NBM-BMX for people with metastatic uveal melanoma, a type of eye cancer that has spread to other parts of the body. The study will help doctors learn about the side effects of NBM-BMX, how the drug is processed in the body, and whether it may slow down or shrink tumors. Participants will take NBM-BMX as a capsule by mouth twice daily on an empty stomach with at least six ounces (180 mL) of water. No food or drink (other than water) should be consumed for at least two hours after each dose. Participants will visit the clinic about once every week or two for exams and blood tests while taking NBM-BMX. After stopping treatment, a follow-up visit will occur about 30 days later. Treatment may continue as long as the cancer does not get worse and side effects remain manageable.
Description
NBM-BMX will be administered orally twice daily (BID) at approximately 12 ± 2-hour intervals for 28 consecutive days per cycle, beginning on Day 1 of Cycle 1. Patients will continue treatment until disease progression, intolerable toxicity likely attributable to NBM-BMX, or voluntary withdrawal from the study. If disease progression is equivocal and, in the investigator's judgment, the patient appears to be benefiting, treatment may continue with close monitoring and re-evaluation at the next scheduled tumor assessment. The study drug will be provided in 100 mg dry powder hard gel capsules. A…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: \- Patients must meet the following criteria to be eligible for study entry: 1. Signed, written IRB-approved informed consent. 2. Men and women age ≥ 18 years 3. ECOG Performance status ≤ 2 4. Have measurable disease based on RECIST 1.1 5. Histologic or cytologic confirmation of metastatic uveal melanoma 6. Previous Therapy * Surgery: Previous surgery is permitted provided that a minimum of 28 days (4 weeks) has elapsed between any major surgery and date of registration, and that wound healing has occurred. * Cytotoxic Chemotherapy: There is no limit to the number…
Interventions
- DrugNBM-BMX Capsule are proprietary products developed by Novelwise Pharmaceutical Corporation (Novelwise) for treatment of patients suffering from cancers.
NBM-BMX is a small molecule inhibitor of HDAC8. The majority of metastasizing uveal melanoma (UM) cases are characterized by the presence of BAP1 mutations. However, as BAP1 mutations lead to a loss of function, therapeutic strategies have primarily focused on exploiting vulnerabilities resulting from BAP1 loss or targeting downstream effectors affected by the BAP1-deficient phenotype. In uveal melanocytes, the absence of BAP1 disrupts their differentiated cell identity, potentially contributing to the metastatic behavior observed in BAP1-mutant UM cells. This differentiation block in the melanocytic lineage is thought to be influenced, at least in part, by the activation of HDAC8 downstream, which leads to the repression of differentiation genes through acetylation of the histone H3K27 at the promoter and enhancers associated with these genes. Consequently, inhibiting HDAC8 could potentially reverse the differentiation block caused by the loss of BAP1.
Locations (3)
- Honor Health Resarch InstituteScottsdale, Arizona
- Sarah Cannon Research Institute (SCRI) - Denver HealthONE LocationDenver, Colorado
- SCRI Oncology PartnersNashville, Tennessee