A Rollover Study of NBM-BMX in Combination With Temozolomide in Patients With Newly Diagnosed Glioblastoma

A Rollover Study to Evaluate the Long-Term Safety and Efficacy of NBM-BMX in Combination With Temozolomide in Patients With Newly Diagnosed Glioblastoma Who Completed Study NBM-BMX-003 (the Parent Study)

This clinical trial is a rollover study designed to provide continued access to NBM-BMX and temozolomide (TMZ) for eligible participants with newly diagnosed glioblastoma who have completed the designated treatment in Study NBM-BMX-003 (the parent study), and to evaluate the long-term safety and efficacy of NBM-BMX administered in combination with TMZ.

This is a multi-center, open-label, single-arm, rollover study designed to provide participants with newly diagnosed glioblastoma who have completed Study NBM-BMX-003 (the parent study) with continued access to study treatment. Eligible participants will transition into this study to continue receiving study drugs (NBM-BMX and temozolomide) at the same doses and schedules as in the parent study.

For participants enrolled in the dose-escalation cohorts of the parent study who received lower doses of NBM-BMX, escalation to a higher dose demonstrated to be safe in the parent study may be permitted with Sponsor approval.

Participants may continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent, death, or up to 12 cycles of treatment, whichever occurs first.

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for the study:

1. Have completed or currently enrolled in Arm B of Study NBM-BMX-003 (the parent study), and in the opinion of the Investigator, may derive clinical benefit from continued treatment with study drugs.

2. Histologically confirmed glioblastoma.

3. Can enroll into this rollover study within 35 days after completing the last dose of NBM-BMX in the parent study.

4. Have signed and dated the informed consent form.

5. Karnofsky performance status (KPS) ≥ 60 at enrollment in this study.

6. Adequate organ functions as defined by the following criteria:

   1. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 3 × upper limit of normal (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

7. Women of childbearing potential must have a negative pregnancy test performed within 14 days before the first dose of this study.

8. Men and women of childbearing potential must agree to use acceptable contraceptive methods throughout the study period and for at least 6 months after the final dose of temozolomide.

   Acceptable contraceptive methods include implants, injectables, combined oral contraceptives, intra-uterine devices (IUDs), sexual abstinence, surgical sterilization or a partner who is sterile.

9. Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.

Exclusion Criteria:

Participants with any of the following will be excluded from the study:

1. Currently receive or plan to receive anti-cancer treatments other than the study drugs including Gliadel wafer implant or tumor treating fields (TTFields).
2. Permanently discontinued from the parent study due to unacceptable toxicity, non-compliance with study procedures, withdrawal of consent, or any other reason.
3. 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.
4. QTcF > 480 msec
5. Currently taking strong inhibitors (e.g., gemfibrozil) or inducers of CYP2C8.
6. Have known hypersensitivity reaction to temozolomide, dacarbazine or NBM-BMX.
7. Have difficulty swallowing (including those require nasogastric tube) or with impaired absorption of oral medications.
8. Female 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.