NBM-BMX is an orally available new chemical entity to inhibit histone deacetylases 8 (HDAC8) activity specifically, being developed as a potential anti-cancer therapeutic by NatureWise. This study aims to evaluate the safety, pharmacokinetics, and preliminary efficacy of NBM-BMX as monotherapy in subjects with advanced solid tumors or combination with the standard of care treatment in subjects with newly diagnosed glioblastoma.
This is a multi-center, open-label, 2-arm, phase Ib/II study to evaluate the safety, pharmacokinetics, and preliminary efficacy of NBM-BMX as monotherapy in the treatment of solid tumors (Arm A) or in combination with radiotherapy/temozolomide in the treatment of glioblastoma (Arm B). Arm A consists of dose escalation cohorts in subjects with advanced solid tumors who will be treated with NBM-BMX monotherapy at different dose levels. Arm B consists of dose escalation cohorts (Phase Ib) and expansion cohorts (Phase II) in subjects with newly diagnosed glioblastoma (GBM). Subjects will be treated with NBM-BMX at different dose levels in combination with the first-line standard of care treatment (i.e., concomitant Radiotherapy (RT)/TMZ followed by adjuvant TMZ) in Phase Ib. After the recommended Phase 2 dose (RP2D) is determined in Phase Ib, additional subjects will be enrolled and treated at the RP2D to evaluate the efficacy of NBM-BMX combination therapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
79
Each capsule contains 100 mg of the active ingredient.
TMZ will be administered orally at a 75 mg/m2 dose daily during concomitant therapy. In the maintenance period, days 1-5 of each cycle will be administered 150-200 mg/m2.
A total dose of 60 Gy will be administered in 6 weeks.
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, Taiwan
NOT_YET_RECRUITINGTaichung Veterans General Hospital
Taichung, Taiwan
RECRUITINGKoo Foundation Sun Yat-Sen Cancer Center
Taipei, Taiwan
RECRUITINGLinkou Chang-Gung Memorial Hospital
Taoyuan City, Taiwan
RECRUITING[Arm A, Phase Ib] Frequency of dose-limiting toxicity (DLT) at each dose level
To determine the maximum tolerated dose (MTD) for NBM-BMX monotherapy in subjects with advanced solid tumors, toxicities will be graded according to the National Cancer Institute Common Terminology.
Time frame: up to 28 days
[Arm B, Phase Ib] Frequency of dose-limiting toxicity (DLT) at each dose level
To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for NBM-BMX in combination with RT and TMZ in subjects with newly diagnosed GBM, toxicities will be graded according to the National Cancer Institute Common Terminology.
Time frame: up to 10 weeks
[Arm B, Phase II] Progression-free survival rate at 6 months (PFS6)
To assess the preliminary efficacy of NBM-BMX in combination with RT and TMZ in subjects with newly diagnosed GBM, the investigators will evaluate anti-tumor activity using RANO criteria.
Time frame: up to 6 months
Frequency, types, severity, and relationship to NBM-BMX of adverse events (AEs)
The severity of AEs will be graded using NCI CTCAE Version 5.0 by the investigator.
Time frame: up to 28 days
Preliminary assessment of anti-tumor activity by response evaluation criteria
Tumor response and progression will be assessed using the RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria.
Time frame: at least 8 weeks
Area under the plasma concentration versus time curve (AUC) of NBM-BMX
Blood samples will be collected at each pre-specified time point for measuring concentrations of NBM-BMX in plasma using a validated bioanalytical method.
Time frame: Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)
Peak plasma concentration (Cmax) of NBM-BMX
Blood samples will be collected at each pre-specified time point for measuring concentrations of NBM-BMX in plasma using a validated bioanalytical method.
Time frame: Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)
Time to maximum plasma concentration (Tmax) of NBM-BMX
Blood samples will be collected at each pre-specified time point for measuring concentrations of NBM-BMX in plasma using a validated bioanalytical method.
Time frame: Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)
Terminal elimination half-life (T1/2) of NBM-BMX
Blood samples will be collected at each pre-specified time point for measuring concentrations of NBM-BMX in plasma using a validated bioanalytical method.
Time frame: Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)
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