Ricolinostat (ACY-1215)

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General information

Class/mechanism: Selective HDAC6 inhibitor. Histone deacetylase (HDAC) inhibitors result in hyperacetylation of histones and modulate gene expression by creating an open chromatin state that leads to expression of previously silenced genes. This modulation may result in decreased expression of oncogenes, induction of cell cycle arrest, promotion of apoptosis, and decreased invasion of tumor cells. It is hypothesized that selectively inhibiting HDAC6 rather than additional members of the HDAC family may be able to maintain efficacy while resulting in fewer side effects associated with pan-HDAC inhibitors, such as myelosuppression, fatigue, nausea, vomiting, and diarrhea.
Route: PO
Extravasation: n/a

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Preliminary data

Multiple myeloma

Lenalidomide, Dexamethasone, Ricolinostat

Regimen, Yee et al. 2014

Doses & schedule of Ricolinostat varied at different points in the study. The regimen below is based on "Part B" as described in Yee et al. 2014.

• Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
• Dexamethasone (Decadron) 40 mg PO once per week
• Ricolinostat (ACY-1215, Rocilinostat) 160 mg PO BID once per day on days 1 to 21

28-day cycles

References

1. Andrew J Yee, MD, Peter M. Voorhees, MD, William Bensinger, Jesus G. Berdeja, MD, Jeffrey G Supko, PhD, Paul G. Richardson, David Tamang, PhD, Simon S Jones, PhD, Gretchen Patrick, Catherine Wheeler, MD and Noopur Raje, MD. Ricolinostat (ACY-1215), a Selective HDAC6 Inhibitor, in Combination with Lenalidomide and Dexamethasone: Results of a Phase 1b Trial in Relapsed and Relapsed Refractory Multiple Myeloma. 2014 ASH Annual Meeting abstract 4772. link to abstract

Bortezomib, Dexamethasone, Rocilinostat

Regimen, Raje et al. 2012

Different doses & schedule of Rocilinostat were used at different points in this Phase I/II Study. Please refer to Raje et al. 2012 regarding the various doses of Rocilinostat used in the monotherapy part.

• Bortezomib (Velcade) 1.0 mg/m2 (route not specified) once per day on days 1, 4, 8, 11
• Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
• Ricolinostat (ACY-1215, Rocilinostat) 40 mg PO (40 mg was the "starting dose." Schedule was not clearly specified; during the monotherapy "Part 1" of the study, it was given on days 1 to 5 and days 8 to 12)

21-day cycles x "up to 6 cycles of therapy, or more if experiencing clinical benefit"

References

1. Vogl DT, Raje N, Jagannath S, Richardson P, Hari P, Orlowski R, Supko JG, Tamang D, Yang M, Jones SS, Wheeler C, Markelewicz RJ, Lonial S. Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination with Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma. Clin Cancer Res. 2017 Jul 1;23(13):3307-3315. Epub 2017 Jan 4. link to original article PubMed

Also known as

ACY-1215, Rocilinostat