A phase 1 clinical trial evaluating marizomib, pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma (NPI-0052-107): final study results

Andrew Spencer, Simon Harrison, Jeffrey Zonder, Ashraf Badros, Jacob Laubach, Krystal Bergin, Amit Khot, Todd Zimmerman, Dharminder Chauhan, Nancy Levin, Ann MacLaren, Steven D. Reich, Mohit Trikha, Paul Richardson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Marizomib (MRZ) is an irreversible, pan-subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low-dose dexamethasone (Lo-DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0·3–0·5 mg/m2) was administered over 2 h on days 1, 4, 8, 11; POM (3–4 mg) on days 1–21; and Lo-DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28-day cycle. Thirty-eight patients were enrolled that had received a median of 4 (range 1–10) prior lines of therapy; all patients received prior lenalidomide and bortezomib. No dose-limiting toxicities (DLTs) were observed and 0·5 mg/m2 MRZ was determined to be the RP2D. The most common treatment-related ≥Grade 3 adverse events were: neutropenia (11/38 patients: 29%), pneumonia (4/38 patients 11%), anaemia (4/38 patients; 11%) and thrombocytopenia (4/38 patients; 11%). The overall response rate and clinical benefit rate was 53% (19/36) and 64% (23/36), respectively. In conclusion, PMD was well tolerated and demonstrated promising activity in heavily pre-treated, high-risk RRMM patients.

Original languageEnglish
Pages (from-to)41-51
Number of pages11
JournalBritish Journal of Haematology
Volume180
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • low-dose dexamethasone
  • marizomib
  • pomalidomide
  • proteasome inhibitor
  • relapsed/refractory multiple myeloma

Cite this

Spencer, Andrew ; Harrison, Simon ; Zonder, Jeffrey ; Badros, Ashraf ; Laubach, Jacob ; Bergin, Krystal ; Khot, Amit ; Zimmerman, Todd ; Chauhan, Dharminder ; Levin, Nancy ; MacLaren, Ann ; Reich, Steven D. ; Trikha, Mohit ; Richardson, Paul. / A phase 1 clinical trial evaluating marizomib, pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma (NPI-0052-107) : final study results. In: British Journal of Haematology. 2018 ; Vol. 180, No. 1. pp. 41-51.
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title = "A phase 1 clinical trial evaluating marizomib, pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma (NPI-0052-107): final study results",
abstract = "Marizomib (MRZ) is an irreversible, pan-subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low-dose dexamethasone (Lo-DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0·3–0·5 mg/m2) was administered over 2 h on days 1, 4, 8, 11; POM (3–4 mg) on days 1–21; and Lo-DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28-day cycle. Thirty-eight patients were enrolled that had received a median of 4 (range 1–10) prior lines of therapy; all patients received prior lenalidomide and bortezomib. No dose-limiting toxicities (DLTs) were observed and 0·5 mg/m2 MRZ was determined to be the RP2D. The most common treatment-related ≥Grade 3 adverse events were: neutropenia (11/38 patients: 29{\%}), pneumonia (4/38 patients 11{\%}), anaemia (4/38 patients; 11{\%}) and thrombocytopenia (4/38 patients; 11{\%}). The overall response rate and clinical benefit rate was 53{\%} (19/36) and 64{\%} (23/36), respectively. In conclusion, PMD was well tolerated and demonstrated promising activity in heavily pre-treated, high-risk RRMM patients.",
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author = "Andrew Spencer and Simon Harrison and Jeffrey Zonder and Ashraf Badros and Jacob Laubach and Krystal Bergin and Amit Khot and Todd Zimmerman and Dharminder Chauhan and Nancy Levin and Ann MacLaren and Reich, {Steven D.} and Mohit Trikha and Paul Richardson",
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Spencer, A, Harrison, S, Zonder, J, Badros, A, Laubach, J, Bergin, K, Khot, A, Zimmerman, T, Chauhan, D, Levin, N, MacLaren, A, Reich, SD, Trikha, M & Richardson, P 2018, 'A phase 1 clinical trial evaluating marizomib, pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma (NPI-0052-107): final study results' British Journal of Haematology, vol. 180, no. 1, pp. 41-51. https://doi.org/10.1111/bjh.14987

A phase 1 clinical trial evaluating marizomib, pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma (NPI-0052-107) : final study results. / Spencer, Andrew; Harrison, Simon; Zonder, Jeffrey; Badros, Ashraf; Laubach, Jacob; Bergin, Krystal; Khot, Amit; Zimmerman, Todd; Chauhan, Dharminder; Levin, Nancy; MacLaren, Ann; Reich, Steven D.; Trikha, Mohit; Richardson, Paul.

In: British Journal of Haematology, Vol. 180, No. 1, 01.01.2018, p. 41-51.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - A phase 1 clinical trial evaluating marizomib, pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma (NPI-0052-107)

T2 - final study results

AU - Spencer, Andrew

AU - Harrison, Simon

AU - Zonder, Jeffrey

AU - Badros, Ashraf

AU - Laubach, Jacob

AU - Bergin, Krystal

AU - Khot, Amit

AU - Zimmerman, Todd

AU - Chauhan, Dharminder

AU - Levin, Nancy

AU - MacLaren, Ann

AU - Reich, Steven D.

AU - Trikha, Mohit

AU - Richardson, Paul

PY - 2018/1/1

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N2 - Marizomib (MRZ) is an irreversible, pan-subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low-dose dexamethasone (Lo-DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0·3–0·5 mg/m2) was administered over 2 h on days 1, 4, 8, 11; POM (3–4 mg) on days 1–21; and Lo-DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28-day cycle. Thirty-eight patients were enrolled that had received a median of 4 (range 1–10) prior lines of therapy; all patients received prior lenalidomide and bortezomib. No dose-limiting toxicities (DLTs) were observed and 0·5 mg/m2 MRZ was determined to be the RP2D. The most common treatment-related ≥Grade 3 adverse events were: neutropenia (11/38 patients: 29%), pneumonia (4/38 patients 11%), anaemia (4/38 patients; 11%) and thrombocytopenia (4/38 patients; 11%). The overall response rate and clinical benefit rate was 53% (19/36) and 64% (23/36), respectively. In conclusion, PMD was well tolerated and demonstrated promising activity in heavily pre-treated, high-risk RRMM patients.

AB - Marizomib (MRZ) is an irreversible, pan-subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low-dose dexamethasone (Lo-DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0·3–0·5 mg/m2) was administered over 2 h on days 1, 4, 8, 11; POM (3–4 mg) on days 1–21; and Lo-DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28-day cycle. Thirty-eight patients were enrolled that had received a median of 4 (range 1–10) prior lines of therapy; all patients received prior lenalidomide and bortezomib. No dose-limiting toxicities (DLTs) were observed and 0·5 mg/m2 MRZ was determined to be the RP2D. The most common treatment-related ≥Grade 3 adverse events were: neutropenia (11/38 patients: 29%), pneumonia (4/38 patients 11%), anaemia (4/38 patients; 11%) and thrombocytopenia (4/38 patients; 11%). The overall response rate and clinical benefit rate was 53% (19/36) and 64% (23/36), respectively. In conclusion, PMD was well tolerated and demonstrated promising activity in heavily pre-treated, high-risk RRMM patients.

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