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.
Signed, written IRB-approved informed consent.
Men and women age ≥ 18 years
ECOG Performance status ≤ 2
Have measurable disease based on RECIST 1.1
Pregnant or nursing women. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation and for at least 6 months after the last dose of NBM-BMX. Should a man father a child, or a woman become pregnant or suspect she is pregnant while participating in this study, he or she should inform the treating physician immediately.
Concurrent non-protocol-specified anti-tumor therapy (e.g., chemotherapy, other targeted therapy, radiation therapy, or photodynamic therapy)
History of other malignancies within 3 years of Day 1, except for tumors with a negligible risk for metastasis or death, such as adequately treated squamous-cell carcinoma of the skin, ductal carcinoma in situ of the breast, or carcinoma in situ of the cervix.
Active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol.
Single group
NBM-BMX Capsule are proprietary products developed by Novelwise Pharmaceutical Corporation (Novelwise) for treatment of patients suffering from cancers.
DrugNBM-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.
Phase Ib: Incidence of dose-limiting toxicities (DLTs)
Participants experiencing a DLT during Cycle 1 (28 days)
Phase Ib: Maximum Tolerated Dose (MTD)
The highest dose level with ≤1 of 6 participants with a DLT, based on the incidence of DLTs at each dose level of NBM-BMX during Cycle 1 (28 days). MTD will inform the recommended Phase 2 dose (RP2D) of NBM-BMX
Phase II: Objective Response Rate (ORR)
Proportion of patients with complete response (CR) + partial response (PR) determined per RECIST 1.1 while on NBM-BMX.
Phase Ib: Safety and Tolerability
Incidence, severity, and type of adverse events graded per NCI CTCAE v5.0
Phase Ib: Objective Response Rate (ORR)
Percentage of participants with confirmed Complete Response (CR) or Partial Response (PR) per RECIST v1.1.
Phase Ib. PK: Maximum plasma concentration (Cmax)
Cmax of NBM-BMX from plasma concentration-time profile (suggested unit: ng/mL)
Phase Ib. PK: Time to Cmax (Tmax)
Tmax of NBM-BMX from plasma concentration-time profile (unit: hours)
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