Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
MRZ · 2 trials · 2 indications
Assess dose-limiting toxicities (DLTs) in each dose-escalation arm
To assess the safety of the combination of MRZ and TMZ with the addition of Optune™ in patients entering Adjuvant Treatment
Radiographic ORR is defined as the percentage of participants achieving a Complete Response (CR) or Partial Response (PR), as assessed by the investigator, according to RANO 2010 criteria. Tumor response assessment was conducted every 2 cycles of study therapy. 95% confidence interval from exact binomial distribution (Clopper-Pearson method).
OS is defined as time from the date of the first dose of study drug to date of death due to any cause. Participants who are alive will be censored at the last follow up visit
| Arm | Type | Description |
|---|---|---|
| Stage 1: Concomitant Treatment | EXPERIMENTAL | MRZ + TMZ + RT Patients who complete Concomitant Treatment may continue on to Adjuvant Treatment. |
| Stage 1: Adjuvant Treatment | EXPERIMENTAL | MRZ + TMZ |
| Stage 2: Dose-Expansion | EXPERIMENTAL | MRZ + TMZ + RT followed by MRZ + TMZ In Stage 2 (dose-expansion): a minimum of 12 and up to approximately 18 additional evaluable patients will be enrolled in a cohort in which Concomitant Treatment (MRZ + TMZ + RT) is followed by Adjuvant Treatment (MRZ + TMZ) to confirm the MTD for each treatment regimen as determined in the Dose-Escalation (Stage 1), and to assess preliminary activity of the recommended Phase 2 dose (RP2D). |
| Optune Arm | EXPERIMENTAL | MRZ + TMZ + Optune |
| Phase 1: MRZ + BEV; Phase 2: MRZ alone | EXPERIMENTAL | Part1-Phase1: MRZ 10 minute IV infusion on Days 1, 8, and 15 plus BEV IV infusion on Days 1 and 15 of each 28-day cycle. Part2-Phase2: MRZ 10 minute IV infusion administered on Days 1, 8, and 15 of each 28-day cycle. Part3-Phase2: All subjects will receive IV MRZ infusion and IV BEV infusion. MRZ will be administered as a 10-minute, IV infusion on Days 1, 8, and 15 of every 28-day cycle using intra-patient dose escalation. Starting dose will be 0.8 mg/m2. Part4- Phase1: All subjects will receive MRZ enterally by NG tube as a bolus on Days 1, 8 and 15 of the first 28-day cycle and BEV IV infusion on Day 15 of the first 28-day cycle. For subsequent 28-day treatment cycles, MRZ will be administered as an IV at the recommended dose and schedule determined in Part 1, with BEV IV on Days 1 and 15. Part5-Phase1: All subjects will receive IV MRZ infusion and IV BEV infusion. MRZ will be administered as a 10-minute, IV infusion at 0.8 mg/m2 on Days 1, 8, and 15 of every 28-day cycle 0.8 mg/m2 |
| Name | Type | Description |
|---|---|---|
| MRZ | DRUG | MRZ dose ranges from 0.55 to 1.2 mg/m2 given IV over 10 minutes on Days 1, 8, 15, 29, and 36 during Concomitant Treatment. MRZ dose ranges from 0.55 to 1.2 mg/m2 given IV over 10 minutes on Days 1, 8, 15 every 28 days during Adjuvant Treatment. IV hydration will be given prior to the MRZ infusion. |
| TMZ | DRUG | TMZ will be administered once daily, 7 days/week, for 6 weeks, starting on Day 1, at a dose of 75 mg/m2 during Concomitant Treatment. TMZ will be administered once daily on Days 1-5 every cycle, dose range 150 to 200 mg/m2 during Adjuvant Treatment. |
| RT | RADIATION | Focal RT will be administered once daily, 5 days/week, for 30 doses over 6 weeks to a total dose of 60 Gy, starting on Day 1 during Concomitant Treatment. |
| Optune | DEVICE | Tumor Treating Fields Therapy device to be worn ≥ 18 hours per day. |
| BEV | DRUG | BEV 10 mg/kg IV infusion administered for all cohorts in Phase 1 only. |
Inclusion Criteria: * Signed Informed Consent Form * Males and females of age ≥ 18 years or of age ≥ 22 years for those assigned to Optune™ at the time of signing of the informed consent document. * Histologically confirmed newly diagnosed G4 MG * Karnofsky Performance Status (KPS) score ≥ 70% * Fo...
MRZ, also known as marizomib, is an investigational small molecule being studied for the treatment of malignant glioma, multiple myeloma, and glioblastoma. It is being developed by Bristol-Myers Squibb Company (BMY) and is currently in Phase 1 clinical development for these oncology indications.
MRZ is a small molecule that targets the proteasome, an enzyme complex that degrades proteins. By inhibiting the proteasome, MRZ disrupts protein homeostasis in cancer cells, leading to cell death. This mechanism is being explored in clinical trials for multiple myeloma and brain cancers.
MRZ is being developed by Bristol-Myers Squibb Company, a biopharmaceutical company listed on the New York Stock Exchange under the ticker symbol BMY. The drug is currently in Phase 1 clinical trials for the treatment of malignant glioma, multiple myeloma, and glioblastoma.
MRZ is currently in Phase 1 clinical development. It has completed one Phase 1 trial and one Phase 2 trial, but the most advanced ongoing development is Phase 1. MRZ is investigational and has not been approved by the FDA for any indication.
MRZ has been studied in three clinical trials. NCT00461045 was a Phase 2 trial in relapsed or relapsed/refractory multiple myeloma. NCT02330562 was a Phase 1 trial of marizomib with or without bevacizumab in glioblastoma. NCT02903069 was a Phase 1 trial of marizomib with temozolomide and radiotherapy in newly diagnosed brain cancer.
Yes, MRZ is also known as marizomib. Clinical trials listed under the name marizomib, such as NCT02330562 and NCT02903069, are studying the same drug. Marizomib is the generic name, while MRZ is a shorthand designation used in research contexts.