Oral treatment with NBM-BMX for patients with solid tumors or glioblastoma

A Phase Ib/II, Open-label Study of NBM-BMX as Monotherapy or in Combination With Radiotherapy and Temozolomide in Subjects With Solid Tumors or Newly Diagnosed Glioblastoma

This study is testing a new oral medication called NBM-BMX to see if it can help people with advanced solid tumors or newly diagnosed glioblastoma, either on its own or alongside standard treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 79 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Novelwise Pharmaceutical Corporation (Industry-sponsored)
• Drugs / interventions: immunotherapy, radiation
• Locations: 4 sites (Kaohsiung City and 3 other locations)
• Trial ID: NCT06012695 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety, pharmacokinetics, and preliminary efficacy of NBM-BMX, a new oral medication targeting histone deacetylases 8 (HDAC8), in patients with advanced solid tumors and newly diagnosed glioblastoma. The study is divided into two arms: one for patients receiving NBM-BMX as a standalone treatment for solid tumors, and another for those receiving it in combination with standard treatments like radiotherapy and temozolomide for glioblastoma. The trial will assess different dosage levels to determine the optimal dose for further evaluation.

Who should consider this trial

Good fit: Ideal candidates include adults over 18 with advanced solid tumors that are refractory to standard treatments or newly diagnosed glioblastoma.

Not a fit: Patients with tumors that are not measurable or evaluable, or those with a performance status worse than ECOG 2, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors and glioblastoma, potentially improving outcomes.

How similar studies have performed: While this approach is novel in its specific targeting of HDAC8, similar studies targeting histone deacetylases have shown promise in other cancer treatments.

Eligibility criteria

Inclusion Criteria:

Arm A (advanced solid tumors)

1. Having signed and dated the informed consent form.
2. Females or males \> 18 years old.
3. Histologically or cytologically confirmed advanced solid tumors refractory to standard of care therapy, or for which no standard of care therapy is available.
4. 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).
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
6. Adequate organ function as defined by the following criteria:

   1. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 3 × upper limits of normal (ULN), unless liver metastases present, then ≤ 5 × ULN
   2. Total serum bilirubin ≤ 1.5 × ULN unless bilirubin elevation is related to Gilbert's Syndrome for which bilirubin ≤ 3 × ULN
   3. Absolute neutrophil count (ANC) ≥ 1,000/μL
   4. Platelets ≥ 75,000/μL
   5. Hemoglobin ≥ 8.0 g/dL
   6. 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.
7. QTcF ≤ 480 msec
8. Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.

Arm B (newly diagnosed GBM)

1. Having signed and dated the informed consent form.
2. Females or males \> 18 years old.
3. Newly diagnosed, histologically confirmed glioblastoma, non-resectable, partially resected or resected.
4. Karnofsky performance status (KPS) ≥ 60 at screening and before the initiation (Day 1) of concomitant therapy.
5. Disease that is measurable or evaluable as defined by Response Assessment in Neuro-Oncology (RANO) criteria.
6. Adequate organ function as defined by the following criteria:

   1. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 3 × upper limit of normal (ULN), unless liver metastases present, then ≤ 5 × ULN
   2. Total serum bilirubin ≤ 1.5 × ULN unless bilirubin elevation is related to Gilbert's Syndrome for which bilirubin ≤ 3 × ULN
   3. Absolute neutrophil count (ANC) ≥ 1,500/μL
   4. Platelets ≥ 100,000/μL
   5. Hemoglobin ≥ 8.0 g/dL
   6. 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.
7. QTcF ≤ 480 msec
8. Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.

Exclusion Criteria:

Arm A (advanced solid tumors)

1. 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.
2. Curative radiation therapy within 28 days or palliative RT within 7 days of the first dose of NBM-BMX.
3. Currently taking strong inhibitors (e.g., gemfibrozil) or inducers of CYP2C8.
4. 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.
5. 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.
6. Known history of human immunodeficiency virus (HIV) infection.
7. 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.
8. Females who are pregnant or breastfeeding.
9. 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)

1. Prior systemic therapy (including Gliadel wafer implant), immunotherapy, investigational agents, or radiotherapy for glioblastoma.
2. Currently taking strong inhibitors (e.g., gemfibrozil) or inducers of CYP2C8.
3. Corticosteroid use of \> 8 mg/day dexamethasone or equivalent within 5 days before the first dose of NBM-BMX.
4. A history of hypersensitivity reaction to temozolomide or dacarbazine.
5. 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.
6. 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.
7. Known history of human immunodeficiency virus (HIV) infection. Note: HIV testing is not required.
8. 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.
9. Female who are pregnant or breastfeeding.
10. 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.

Where this trial is running

Kaohsiung City and 3 other locations

• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City, Taiwan (Not_yet_recruiting)
• Taichung Veterans General Hospital — Taichung, Taiwan (Recruiting)
• Koo Foundation Sun Yat-Sen Cancer Center — Taipei, Taiwan (Recruiting)
• Linkou Chang-Gung Memorial Hospital — Taoyuan City, Taiwan (Recruiting)

Study contacts

• Study coordinator: Chia-Chung Hou, Ph.D.

Conditions Malignant Neoplasm; Malignant Neoplasm of Brain