A phase 1 study of filanesib, carfilzomib, and dexamethasone in patients with relapsed and/or refractory multiple myeloma

Lee, Hans C.; Shah, Jatin J.; Liu, Feng; Manasanch, Elisabet E.; Lu, Rebecca; Morphey, Ashley; Crumpton, Brandon N.; Patel, Krina; Wang, Michael L.; Alexanian, Raymond; Thomas, Sheeba K.; Weber, Donna M.; Orłowski, Robert Z.

doi:10.1038/s41408-019-0240-6

Cited by 20 publications

(6 citation statements)

References 8 publications

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“…Another triplet combination of filanesib, bortezomib, and dexamethasone was assessed in a phase I trial conducted in patients with RRMM and showed some durable responses in RRMM patients (Chari et al, 2016). In a phase I study, the combination of filanesib, carfilzomib, and dexamethasone was demonstrated to be safe and to have few side effects though the efficacy of this combination was limited (Lee et al, 2019). The dose-limiting toxicity of filanesib in these cited studies was neutropenia.…”

Section: Spindle Assembly Checkpoint and Microtubule Inhibitorsmentioning

confidence: 99%

Drug Targeting of Genomic Instability in Multiple Myeloma

Beksaç

Balli²,

Yildiz

2020

Front. Genet.

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Section: Spindle Assembly Checkpoint and Microtubule Inhibitorsmentioning

confidence: 99%

Drug Targeting of Genomic Instability in Multiple Myeloma

Beksaç

Balli²,

Yildiz

2020

Front. Genet.

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“…The overall survival of 19 months were obtained with Arry-520 as mono therapy and 10,7 months in combination with dexamethasone. These encouraging results prompted the exploration of potential combinations with proteasome inhibitors such as bortezomib [110] and carfilzomib [111] [112] in combination with or without dexamethasone. Combining Arry-520 with the proteasome inhibitor bortezomib produced response rates as high as 42 %.…”

Section: Results Of the Clinical Trialsmentioning

confidence: 99%

Eg5 targeting agents: From new anti-mitotic based inhibitor discovery to cancer therapy and resistance

Garcia-Saez

Skoufias

2021

Biochemical Pharmacology

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“…The IC 50 of LGI-147 on cell viability at the pM level was extremely low. The therapeutic potential of other Eg5 inhibitors such as AZD4877 [ 26 , 27 ] and filanesib [ 28 , 29 , 30 ] has been demonstrated in several phase I or II clinical trials for cancers other than HCC. Our findings may provide a basis for the development of LGI-147 or other Eg5 inhibitors as HCC therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Eg5 as a Prognostic Biomarker and Potential Therapeutic Target for Hepatocellular Carcinoma

Shao

Sun

Jeng

et al. 2021

Cells

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Background: The kinesin Eg5, a mitosis-associated protein, is overexpressed in many cancers. Here we explored the clinical significance of Eg5 in hepatocellular carcinoma (HCC). Methods: HCC tissues from surgical resection were collected. Total RNA was prepared from tumorous and nontumorous parts. Eg5 expression levels were correlated with overall survival (OS) and disease-free survival (DFS). In vitro efficacy of LGI-147, a specific Eg5 inhibitor, was tested in HCC cell lines. In vivo efficacy of Eg5 inhibition was investigated in a xenograft model. Results: A total of 108 HCC samples were included. The patients were divided into three tertile groups with high, medium, and low Eg5 expression levels. OS of patients with low Eg5 expression was better than that of patients with medium and high Eg5 expression (median, 155.6 vs. 75.3 vs. 57.7 months, p = 0.002). DFS of patients with low Eg5 expression was also better than that of patients with medium and high Eg5 expression (median, 126.3 vs. 46.2 vs. 39.4 months, p = 0.001). In multivariate analyses, the associations between Eg5 expression and OS (p < 0.001) or DFS remained (p < 0.001). LGI-147 reduced cell growth via cell cycle arrest and apoptosis and induced accumulation of abnormal mitotic cells. In the xenograft model, the tumor growth rate under LGI-147 treatment was significantly slower than under the control. Conclusion: High Eg5 expression was associated with poor HCC prognosis. In vitro and in vivo evidence suggests that Eg5 may be a reasonable therapeutic target for HCC.

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A phase 1 study of filanesib, carfilzomib, and dexamethasone in patients with relapsed and/or refractory multiple myeloma

Cited by 20 publications

References 8 publications

Drug Targeting of Genomic Instability in Multiple Myeloma

Drug Targeting of Genomic Instability in Multiple Myeloma

Eg5 targeting agents: From new anti-mitotic based inhibitor discovery to cancer therapy and resistance

Eg5 as a Prognostic Biomarker and Potential Therapeutic Target for Hepatocellular Carcinoma

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