Status:

RECRUITING

NBM-BMX Administered Orally to Patients with Solid Tumors or Newly Diagnosed Glioblastoma

Lead Sponsor:

Novelwise Pharmaceutical Corporation

Conditions:

Malignant Neoplasm

Malignant Neoplasm of Brain

Eligibility:

All Genders

18+ years

Phase:

PHASE1

PHASE2

Brief Summary

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 aim...

Detailed Description

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...

Eligibility Criteria

Inclusion

  • Arm A (advanced solid tumors)
  • Having signed and dated the informed consent form.
  • Females or males \> 18 years old.
  • Histologically or cytologically confirmed advanced solid tumors refractory to standard of care therapy, or for which no standard of care therapy is available.
  • Disease that is measurable or evaluable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria (for CNS tumors).
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
  • Adequate organ function as defined by the following criteria:
  • Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 3 × upper limits of normal (ULN), unless liver metastases present, then ≤ 5 × ULN
  • Total serum bilirubin ≤ 1.5 × ULN unless bilirubin elevation is related to Gilbert's Syndrome for which bilirubin ≤ 3 × ULN
  • Absolute neutrophil count (ANC) ≥ 1,000/μL
  • Platelets ≥ 75,000/μL
  • Hemoglobin ≥ 8.0 g/dL
  • Non-indexed estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73 m2 × BSA (m2)/1.73.
  • Transfusion is not allowed to meet entry criteria.
  • QTcF ≤ 480 msec
  • Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
  • Arm B (newly diagnosed GBM)
  • Having signed and dated the informed consent form.
  • Females or males \> 18 years old.
  • Newly diagnosed, histologically confirmed glioblastoma, non-resectable, partially resected or resected.
  • Karnofsky performance status (KPS) ≥ 60 at screening and before the initiation (Day 1) of concomitant therapy.
  • Disease that is measurable or evaluable as defined by Response Assessment in Neuro-Oncology (RANO) criteria.
  • Adequate organ function as defined by the following criteria:
  • Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 3 × upper limit of normal (ULN), unless liver metastases present, then ≤ 5 × ULN
  • Total serum bilirubin ≤ 1.5 × ULN unless bilirubin elevation is related to Gilbert's Syndrome for which bilirubin ≤ 3 × ULN
  • Absolute neutrophil count (ANC) ≥ 1,500/μL
  • Platelets ≥ 100,000/μL
  • Hemoglobin ≥ 8.0 g/dL
  • Non-indexed estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 × BSA (m2)/1.73.
  • Transfusion is not allowed to meet entry criteria.
  • QTcF ≤ 480 msec
  • Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.

Exclusion

  • Arm A (advanced solid tumors)
  • Systemic anti-cancer treatment (investigational or approved) within 28 days or 5 half-lives of that drug (whichever is shorter) of the first dose of NBM-BMX.
  • Curative radiation therapy within 28 days or palliative RT within 7 days of the first dose of NBM-BMX.
  • Currently taking strong inhibitors (e.g., gemfibrozil) or inducers of CYP2C8.
  • Any of the following within 6 months of the first dose of NBM-BMX: pulmonary embolism events, deep vein thrombosis (DVT) events, myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack.
  • 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.
  • Known history of human immunodeficiency virus (HIV) infection.
  • Men and women of childbearing potential who are unwilling to use highly effective contraceptive methods during the study period.
  • Highly effective contraceptive methods include implants, injectables, combined oral contraceptives, intra-uterine devices (IUDs), sexual abstinence, surgical sterilization or a partner who is sterile.
  • Females who are pregnant or breastfeeding.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would impart, in the judgement of the investigator and/or sponsor, excess risks associated with study participation or study drug administration.
  • Arm B (newly diagnosed GBM)
  • Prior systemic therapy (including Gliadel wafer implant), immunotherapy, investigational agents, or radiotherapy for glioblastoma.
  • Currently taking strong inhibitors (e.g., gemfibrozil) or inducers of CYP2C8.
  • Corticosteroid use of \> 8 mg/day dexamethasone or equivalent within 5 days before the first dose of NBM-BMX.
  • A history of hypersensitivity reaction to temozolomide or dacarbazine.
  • Any of the following within 6 months of the first dose of NBM-BMX: pulmonary embolism events, deep vein thrombosis (DVT) events, myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack.
  • 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.
  • Known history of human immunodeficiency virus (HIV) infection. Note: HIV testing is not required.
  • Men and women of childbearing potential who are unwilling to use highly effective contraceptive methods during the study period and for at least 6 months after the final dose of temozolomide.
  • Highly effective contraceptive methods include implants, injectables, combined oral contraceptives, intra-uterine devices (IUDs), sexual abstinence, surgical sterilization or a partner who is sterile.
  • Female who are pregnant or breastfeeding.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would impart, in the judgement of the investigator and/or sponsor, excess risks associated with study participation or study drug administration.

Key Trial Info

Start Date :

August 11 2023

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

September 30 2029

Estimated Enrollment :

79 Patients enrolled

Trial Details

Trial ID

NCT06012695

Start Date

August 11 2023

End Date

September 30 2029

Last Update

November 14 2024

Active Locations (5)

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Page 1 of 2 (5 locations)

1

Hualien Tzu Chi Hospital

Hualien City, Taiwan, 970

2

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan, 807

3

Taichung Veterans General Hospital

Taichung, Taiwan, 407

4

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, Taiwan, 112