FDA Grants Fast Track Status to NBM-BMX for Metastatic Uveal Melanoma

The FDA has granted fast track designation to the selective HDAC8 inhibitor NBM-BMX for use as a therapeutic option in patients with metastatic uveal melanoma, according to an announcement from NovelWise Pharmaceutical Corporation.¹

The agent is designed to moderate epigenetic mechanisms in solid tumors, and for uveal melanoma, BAP1-associated epigenetic dysregulation is known to have an important role in tumor progression. The decision is supported by preclinical findings in uveal melanoma models, and by safety data from prior phase 1 clinical studies. The phase 1/2 NBM-BMX-UM trial (NCT07136181) will further evaluate the safety, efficacy, and pharmacokinetics (PK) of the agent in those with metastatic uveal melanoma.²

“This designation will facilitate more efficient regulatory interactions and clinical planning, helping shorten the time needed to bring new treatment options to patients in need,” according to the news release issued by NovelWise.¹

What Is the Design of the Phase 1/2 Study of NBM-BMX?

The study, which is not yet recruiting, will enroll patients with histologically or cytologically confirmed metastatic uveal melanoma who are at least 18 years of age, have an ECOG performance status no higher than 2, and measurable disease by RECIST 1.1 criteria.²

Moreover, prior surgery is allowed as long as at least 28 days have passed between the surgery and trial enrollment. No limit has been set to number of previous cytotoxic chemotherapy regimens or prior systemic therapies for metastatic disease. Patients are required to have acceptable hematopoietic capacity, hepatic function, and renal function.

Patients receiving concurrent non–protocol-specified antitumor therapy, those with a history of other malignancies within 3 years of day 1 of the study, those with active or uncontrolled infections, a history of disease or metabolic dysfunction, or those currently receiving moderate-to-strong inhibitors or inducers of CYP2C8, will be excluded.

NBM-BMX will be examined at four dose levels: 200 mg daily or 100 mg twice daily (dose level 1), 400 mg daily or 200 mg twice daily (dose level 2), 600 mg daily or 300 mg twice daily (dose level 3), and 800 mg daily or 400 mg twice daily (dose level 4).

According to ClinicalTrials.gov, a total daily dose of 600 mg dry powder formulation has been deemed to be well tolerated in patients with advanced solid tumors. Three patients completed treatment with the agent at this level without experiencing dose-limiting toxicities (DLTs). As such, the 200-mg daily dose is hypothesized to be pharmacologically active and safe.

The primary outcome measures for the phase 1b portion of the study are to evaluate incidence of DLTs and determine the maximum tolerated dose (MTD). Secondary outcome measures for this portion will be to examine safety and tolerability, objective response rate (ORR), and PK parameters. For the phase 2 portion, the primary outcome measures include ORR, 3-month progression-free survival (PFS) rate, and overall survival.

What Other Studies Are, or Have, Examined NBM-BMX?

A prior open-label, phase 1, dose-escalation study (NCT03726294) examined the safety, tolerability, PK and efficacy of the agent in patients with advanced solid tumors.³ Patients had to have advanced, nonresectable and/or metastatic solid tumors that were refractory to standard treatment or for whom no standard treatment was available. Patients initially received the agent at a once-daily dose of 100 mg. The primary outcome measures were DLTs and MTD. Secondary outcome measures included antitumor activity and PK parameters. This trial has been completed.

Another open-label, phase 1, dose-escalation study (NCT03808870) examined the safety, tolerability, PK, and efficacy of NBM-BMX in Asian patients with advanced solid tumors.⁴ Again, patients needed to have advanced, nonresectable and/or metastatic solid tumors that were refractory to standard treatment or for whom no standard treatment was available. They needed to be at least 20 years of age, have an ECOG performance status no higher than 2, and have recovered from prior treatment-associated effects to at least grade 1 except for grade 2 alopecia. They also needed to have acceptable organ function.

These patients also received the agent at a once-daily dose of 100 mg. The primary outcome measures were DLTs and MTD. Secondary outcome measures were early antitumor activity in the form of responses and PK parameters. This study has also been completed.

NBM-BMX is also under evaluation as a monotherapy in patients with advanced solid tumors (arm A) or in combination with standard-of-care treatment in those with newly diagnosed glioblastoma (arm B), as part of an open-label, multicenter, 2-arm, phase 1b/2 trial (NCT06012695), which is currently recruiting.⁵

To participate, patients need to be at least 18 years of age, have measurable disease, an ECOG performance status ranging from 0 to 2, and acceptable organ function. For arm B, patients need to be at least 18 years of age, have newly diagnosed, histologically confirmed glioblastoma, a Karnofsky performance status of at least 60, measurable disease by Response Assessment in Neuro-Oncology criteria, and adequate organ function.

Arm A will include dose-escalation cohorts of patients with advanced solid tumors, and the agent will be explored at several dose levels. Arm B will have both a dose-escalation and -expansion cohort in those with newly diagnosed glioblastoma. NBM-BMX will be examined at different dose levels in combination with standard treatment comprised of concomitant radiation at a total dose of 60 Gy in 6 weeks/temozolomide at 75 mg/m² followed by adjuvant temozolomide. In the maintenance period, temozolomide will be given on days 1 to 5 of each treatment cycle at doses ranging from 150 mg/m² to 200 mg/m².

For arms A and B, phase 1b, the primary objectives are to evaluate DLTs at each dose level. For phase 2 in arm B, the primary objective is to look at 6-month PFS rate.

“Insights from that program are expected to further optimize the development strategy for metastatic uveal melanoma,” according to the news release issued by NovelWise.¹

References

1. Novelwise Pharmaceutical receives US FDA fast track designation for NBM-BMX in metastatic uveal melanoma. News release. October 14, 2025. Accessed October 20, 2025. https://www.novelwiseoncology.com/exhibition-information
2. Evaluation of the safety, efficacy, and pharmacokinetics of NBM-BMX in patients with metastatic uveal melanoma (NBM-BMX-UM). ClinicalTrials.gov. Updated August 22, 2025. Accessed October 20, 2025. https://clinicaltrials.gov/study/NCT07136181
3. A safety and pharmacokinetic study of NBM-BMX administered orally to patients with advanced cancer. ClinicalTrials.gov. Updated April 13, 2022. Accessed October 20, 2025. https://clinicaltrials.gov/study/NCT03726294
4. A safety and pharmacokinetic study of NBM-BMX administered orally to Asian patients with advanced cancer. ClinicalTrials.gov. Updated August 15, 2025. Accessed October 20, 2025. https://clinicaltrials.gov/study/NCT03808870
5. NBM-BMX administered orally to patients with solid tumors or newly diagnosed glioblastoma. ClinicalTrials.gov. Updated November 14, 2025. Accessed October 20, 2025. https://clinicaltrials.gov/study/NCT06012695