Evaluation of the Safety, Efficacy, and Pharmacokinetics of NBM-BMX in Patients With Metastatic Uveal Melanoma

NCT07136181 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: NBM-BMX-004IND177628
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Metastatic Uveal Melanoma; Uveal Melanoma, Metastatic; Uveal Melanoma, Recurrent; Eye Cancer, Intraocular Melanoma; Eye Cancer

Keywords

Metastatic Uveal Melanoma; Uveal Melanoma; Eye Cancer; Intraocular Melanoma; Choroidal Melanoma; NBM-BMX; Histone Deacetylase Inhibitor (HDAC inhibitor); Phase 1b/2 Study; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• Phase Ib: Incidence of dose-limiting toxicities (DLTs)

  Participants experiencing a DLT during Cycle 1 (28 days)

  Time Frame: Cycle 1 (up to 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

  Cycle 1 (up to 28 days)

• 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.

  Assessed every 8-12 weeks from first dose; up to ~24 months

Secondary Outcomes (10)

• Phase Ib: Safety and Tolerability

  From first dose through 30 days after last dose (up to ~25 months)

• Phase Ib: Objective Response Rate (ORR)

  Assessed every 8 -12 weeks from first dose; up to ~24 months

• Phase Ib. PK: Maximum plasma concentration (Cmax)

  Cycle 1 Day 1: pre-dose to 12 hours post-dose

• Phase Ib. PK: Time to Cmax (Tmax)

  Cycle 1 Day 1: pre-dose to 12 hours post-dose

• Phase Ib. PK: Area under the curve (AUC 0-12)

  Cycle 1 Day 1: pre-dose to 12 hours post-dose

Study Arms (1)

In the present Phase Ib/II study, up to three dose levels are planned

EXPERIMENTAL

NBM-BMX is a small molecule inhibitor of HDAC8 currently in Phase I testing that has demonstrated activity in a metastatic UM patient. Given the role of the HDAC8 pathway on development and growth of uveal melanoma and the initial clinical activity in the UM setting, there is a high probability that NBM-BMX would have efficacy in this disease In the present Phase Ib/II study, up to four dose levels are planned: * Dose Level 1: 200 mg daily (100 mg BID) * Dose Level 2: 400 mg daily (200 mg BID) * Dose Level 3: 600 mg daily (300 mg BID) * Dose Level 4: 800 mg daily (400 mg BID) A total daily dose of 600 mg (300 mg BID) of the NBM-BMX dry powder formulation has been well tolerated in patients with advanced solid tumors. As three subjects have completed treatment at this dose level without evidence of DLTs, the 200 mg/day dose selected for this trial represents two full dose levels below the highest tolerated dose and is expected to be both safe and pharmacologically active.

Drug: NBM-BMX Capsule are proprietary products developed by Novelwise Pharmaceutical Corporation (Novelwise) for treatment of patients suffering from cancers.

Interventions

NBM-BMX Capsule are proprietary products developed by Novelwise Pharmaceutical Corporation (Novelwise) for treatment of patients suffering from cancers. DRUG

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.

In the present Phase Ib/II study, up to three dose levels are planned

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Patients must meet the following criteria to be eligible for study entry:
• Signed, written IRB-approved informed consent.
• Men and women age ≥ 18 years
• ECOG Performance status ≤ 2
• Have measurable disease based on RECIST 1.1
• Histologic or cytologic confirmation of metastatic uveal melanoma
• 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 of prior regimens received.
• Other Systemic Therapy: There is no limit to the number of prior therapies received for metastatic uveal melanoma. Prior treatment with tebentafusp is required for HLA-A\*02:01-positive patients unless unavailable or clinically inappropriate, as determined by the investigator. Prior HDAC inhibitor treatment is not permitted.
• Patients must have recovered (to baseline or ≤ grade 1) from all reversible toxicity related to prior chemotherapy or systemic therapy and have adequate washout as follows:
• Longest of one of the following:
• Two weeks,
• half-lives for investigational agents,
• o For anti-cancer therapies with half-lives \> 8 days, a washout period of at least 28 days will be acceptable,

You may not qualify if:

• Patients who meet the following criteria will be excluded from study entry:
• 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.
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or renders the patient at high risk from treatment complications.
• Difficulty with swallowing oral medications.
• Currently taking moderate and strong inhibitors (e.g., gemfibrozil) or inducers of CYP2C8.
• A positive test for hepatitis B (HBsAg) and/or hepatitis C (anti-HCV antibody), unless the HBV DNA level and/or HCV RNA level is below the limit of detection.
• Any of the following within 3 months of the first dose of NBM-BMX: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack.
• Current use or anticipated need for P-gp or BCRP inhibitors during the study period.
• Use of proton pump inhibitors (PPIs), H2-receptor antagonists, or other systemic acid-reducing agents within 7 days prior to Cycle 1 Day 1 or planned use during the study treatment period, unless the patient can be switched to local antacids (e.g., calcium carbonate or aluminum hydroxide) taken at least 2 hours before or after NBM-BMX dosing.
• Patients unable or unwilling to comply with this restriction should be excluded. Exceptions must be discussed with and approved by the Medical Monitor.

Sponsors & Collaborators

• Novelwise Pharmaceutical Corporation: lead

Study Sites (3)

Honor Health Resarch Institute

Scottsdale, Arizona, 85258, United States

RECRUITING

Sarah Cannon Research Institute (SCRI) - Denver HealthONE Location

Denver, Colorado, 80218, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

Related Publications (3)

• Char DH, Kroll SM, Castro J. Ten-year follow-up of helium ion therapy for uveal melanoma. Am J Ophthalmol. 1998 Jan;125(1):81-9. doi: 10.1016/s0002-9394(99)80238-4.

  PMID: 9437317 RESULT

• Yang W, Feng Y, Zhou J, Cheung OK, Cao J, Wang J, Tang W, Tu Y, Xu L, Wu F, Tan Z, Sun H, Tian Y, Wong J, Lai PB, Chan SL, Chan AW, Tan PB, Chen Z, Sung JJ, Yip KY, To KF, Cheng AS. A selective HDAC8 inhibitor potentiates antitumor immunity and efficacy of immune checkpoint blockade in hepatocellular carcinoma. Sci Transl Med. 2021 Apr 7;13(588):eaaz6804. doi: 10.1126/scitranslmed.aaz6804.

  PMID: 33827976 RESULT

• Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, Hawkins BS, Hayman JA, Jaiyesimi I, Jampol LM, Kirkwood JM, Koh WJ, Robertson DM, Shaw JM, Straatsma BR, Thoma J; Collaborative Ocular Melanoma Study Group. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol. 2005 Dec;123(12):1639-43. doi: 10.1001/archopht.123.12.1639.

  PMID: 16344433 RESULT

MeSH Terms

Conditions

Uveal Melanoma; Neoplasm Metastasis; Recurrence; Eye Neoplasms

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Central Study Contacts

Annie Pai, PhD

CONTACT

1 (910) 297-9045; NWP-US-info.tw@novelwisepharma.com

John Soong, MD

CONTACT

johnjsoong@novelwisepharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2025
• First Posted: August 22, 2025
• Study Start: November 20, 2025
• Primary Completion (Estimated): March 28, 2028
• Study Completion (Estimated): August 30, 2029
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)