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Also known as NPI-0052, Marizomib
MRZ · 3 trials · 3 indications
Disease response and progression were determined by the investigator using the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). Overall response rate includes patients with a best response of PR of better. Stringent complete response (CR) includes immunophenotypic CR and molecular CR in addition to stringent CR.
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 |
|---|---|---|
| MRZ 0.5 mg/m^2 | EXPERIMENTAL | Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles |
| 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 0.5 mg/m^2 | DRUG | NPI-0052 0.5 mg/m2 administered IV over 2 hours on Days 1, 4, 8, and 11 in each 21-day cycle |
| 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: Prior to Amendment 13: * Age 18 years. * Karnofsky Performance Status (KPS) score 70%. * All patients must have histologic evidence of multiple myeloma. Evidence of relapsed or relapsed/refractory disease for which no other approved treatment is available and clinically indicate...
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MRZ is an investigational small molecule oncology drug being developed by Bristol-Myers Squibb Company (NYSE: BMY). It is being studied in glioblastoma, malignant glioma, and multiple myeloma. MRZ is in Phase 1 clinical development and has been evaluated in completed clinical trials.
MRZ has been studied in glioblastoma and malignant glioma. One completed Phase 1 trial, NCT02903069, evaluated MRZ with temozolomide and radiotherapy in patients with newly diagnosed brain cancer. Another completed Phase 1 trial, NCT02330562, studied MRZ alone and in combination with bevacizumab in WHO Grade IV glioblastoma.
MRZ is being developed by Bristol-Myers Squibb Company, which trades under the ticker BMY. The company is the sponsor of the clinical trials evaluating MRZ in brain cancer and multiple myeloma.
MRZ is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. The completed trials include Phase 1 studies in glioblastoma and malignant glioma, and a Phase 2 trial in relapsed or relapsed/refractory multiple myeloma.
MRZ has been evaluated in completed clinical trials including NCT02903069, a Phase 1 study of MRZ with temozolomide and radiotherapy in newly diagnosed brain cancer, NCT02330562, a Phase 1 study in WHO Grade IV glioblastoma, and NCT00461045, a Phase 2 trial in relapsed or relapsed/refractory multiple myeloma.