Combined with low-dose dexamethasone, marizomib is active in and generally well-tolerated by heavily pretreated patients with relapsed/refractory multiple myeloma, according to a study published in Clinical Cancer Research.1
Marizomib is an irreversible proteasome inhibitor that has demonstrated activity and specificity that is distinct from other proteasome inhibitors, such as bortezomib and carfilzomib. For the present phase 1 study researchers evaluated the maximum tolerated dose, pharmacokinetics, and pharmacodynamics of 2 dosing schedules of intravenous marizomib.
Investigators enrolled 42 patients with advanced malignancies to receive schedule A, and 44 patients with relapsed and/or refractory multiple myeloma and other hematologic malignancies to receive schedule B: schedule A consisted of marizomib 0.1 to 0.9 mg/m2 over 1 to 10 minutes on days 1, 8, and 15 in 4-week cycles, while marizomib in schedule B was given at a dose of 0.075 to 0.6 mg/m2 over 1 minute to 2 hours on days 1, 4, 8, and 11 in 3-week cycles.
The overall response rate was 11% among the 27 evaluable patients with relapsed and/or refractory with multiple myeloma. Responses included 1 very good partial response, 3 partial responses, 4 minimal responses, and 12 patients with stable disease.
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The most common treatment-related adverse events in the schedule A group were fatigue, diarrhea, and infusion site pain, and the most frequent in the schedule B arm was fatigue.
One patient with transformed marginal zone lymphoma in the schedule A group achieved a complete response.
- Harrison SJ, Mainwaring P, Price T, et al. Phase I clinical trial of marizomib (NPI-0052) in patients with advanced malignancies including multiple myeloma: Study NPI-0052-102 final results. Clin Cancer Res. 2016 Jul 29. doi: 10.1158/1078-0432.CCR-15-2616 [Epub ahead of print]