Fimepinostat

First-in-Class Suppressor of MYC

(Oral, Small Molecule HDAC/PI3K Inhibitor)

Fimepinostat (formerly known as CUDC-907) is a synthetic, orally-available, small molecule that potently inhibits the activity of histone deacetylase, or HDAC, and phosphotidyl-inositol 3 kinase, or PI3 kinase enzymes1.

In 2018, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for the development of fimepinostat in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. In 2015, the FDA granted fimepinostat orphan drug designation for the treatment of patients with DLBCL.

In 2013, Curis initiated a Phase 1 clinical study to determine the maximum tolerated dose, recommended Phase 2 dose (RP2D) and preliminary anti-cancer activity of fimepinostat monotherapy in patients with relapsed or refractory lymphomas or multiple myeloma2. In this Phase 1 trial, 9 objective responses (3 complete responses and 6 partial responses) were reported in 21 response-evaluable patients out of a total of 25 patients with relapsed/refractory DLBCL enrolled in the study. In a retrospective post-hoc analysis, 5 of the 9 patients who achieved objective responses had tumors with confirmed MYC oncogene alterations. One of the 9 patients had tumors confirmed as MYC negative and 3 of the 9 patients had tumors whose MYC status could not be determined.

The recommended dose of fimepinostat for further Phase 2 development (RP2D) was determined to be once-daily oral administration of 60 mg dose using a 5 days “on” and 2 days “off” schedule, in 21-day cycles. The most common drug-related adverse events (AEs) reported in the study were low grade (Grade 1 and 2) diarrhea, fatigue and nausea. Dose limiting toxicities (DLTs) consisted of diarrhea and hyperglycemia, however no DLTs occurred at the RP2D. Other drug-related Grade 3 or Grade 4 AEs reported in 3 or more patients included thrombocytopenia and neutrophil decrease (hematologic AEs) as well as diarrhea, hyperglycemia and fatigue (non-hematologic AEs).

The Company also previously evaluated fimepinostat in a Phase 1 combination study with venetoclax, a BCL2 inhibitor, in DLBCL patients, including patients with translocations in both MYC and the BCL2 gene, also referred to as double-hit lymphoma, or high-grade B-cell lymphoma (HGBL), but discontinued the study in March 2020 due to lack of efficacy.

Fimepinostat (formerly known as CUDC-907) is a synthetic, orally-available, small molecule that potently inhibits the activity of histone deacetylase, or HDAC, and phosphotidyl-inositol 3 kinase, or PI3 kinase enzymes1. The Company is currently evaluating fimepinostat in a Phase 1 combination study with venetoclax, a BCL2 inhibitor, in diffuse large B-cell lymphoma (DLBCL) patients, including patients with translocations in both MYC and the BCL2 gene, also referred to as double-hit lymphoma, or high-grade B-cell lymphoma (HGBL).

In May 2018, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for the development of fimepinostat in adult patients with relapsed or refractory DLBCL after two or more lines of systemic therapy. In April 2015, the FDA granted fimepinostat orphan drug designation for the treatment of patients with DLBCL.

In 2013, Curis initiated a Phase 1 clinical study to determine the maximum tolerated dose, recommended Phase 2 dose (RP2D) and preliminary anti-cancer activity of fimepinostat monotherapy in patients with relapsed or refractory lymphomas or multiple myeloma2. In this Phase 1 trial, 9 objective responses (3 complete responses and 6 partial responses) were reported in 21 response-evaluable patients out of a total of 25 patients with relapsed/refractory DLBCL enrolled in the study. In a retrospective post-hoc analysis, 5 of the 9 patients who achieved objective responses had tumors with confirmed MYC oncogene alterations. One of the 9 patients had tumors confirmed as MYC negative and 3 of the 9 patients had tumors whose MYC status could not be determined.

The recommended dose of fimepinostat for further Phase 2 development (RP2D) was determined to be once-daily oral administration of 60 mg dose using a 5 days “on” and 2 days “off” schedule, in 21-day cycles. The most common drug-related adverse events (AEs) reported in the study were low grade (Grade 1 and 2) diarrhea, fatigue and nausea. Dose limiting toxicities (DLTs) consisted of diarrhea and hyperglycemia, however no DLTs occurred at the RP2D. Other drug-related Grade 3 or Grade 4 AEs reported in 3 or more patients included thrombocytopenia and neutrophil decrease (hematologic AEs) as well as diarrhea, hyperglycemia and fatigue (non-hematologic AEs).

Additionally, Curis investigated fimepinostat in conjunction with rituximab in patients with relapsed/refractory DLBCL in the expansion part of the Phase 1 clinical study in order to assess tolerability and preliminary efficacy of the combination regimen. Based on the results of the Phase 1 trial in Q1 2016, Curis initiated a Phase 2 trial to examine the efficacy of fimepinostat in patients with MYC altered relapsed/refractory DLBCL.

For more information on current trials click here.

Posters and Presentations

1 Qian C, et al., Cancer Network Disruption by a Single Molecule Inhibitor Targeting Both Histone Deacetylase Activity and Phosphatidylinositol 3-Kinase Signaling. Clin Cancer Res (2012) 18 (15): 4104–4113https://doi.org/10.1158/1078-0432.CCR-12-0055

2 Younes A, et al., Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial. The Lancet. Oncology, 31 Mar 2016, 17(5):622-631. https://doi.org/10.1016/s1470-2045(15)00584-7


Moffitt Cancer Center
1320)
1322)

MAtch:1322 / 1322 /1950-Moffitt Cancer Center


This Location ALREADY exists:Moffitt Cancer Center
Winship Cancer Institute
1320)
1322)

MAtch:1322 / 1322 /1950-Winship Cancer Institute


This Location ALREADY exists:Winship Cancer Institute
Northwestern Memorial Hospital
1320)
1322)

MAtch:1322 / 1322 /1950-Northwestern Memorial Hospital


This Location ALREADY exists:Northwestern Memorial Hospital
University of Chicago Medical Center
1320)
1322)

MAtch:1322 / 1322 /1950-University of Chicago Medical Center


This Location ALREADY exists:University of Chicago Medical Center
Dana Farber Cancer Institute
1320)
1322)

MAtch:1322 / 1322 /1950-Dana Farber Cancer Institute


This Location ALREADY exists:Dana Farber Cancer Institute
Oncology Hematology West, PC dba Nebraska Cancer Specialists
1320)
1322)

MAtch:1322 / 1322 /1950-Oncology Hematology West, PC dba Nebraska Cancer Specialists


This Location ALREADY exists:Oncology Hematology West, PC dba Nebraska Cancer Specialists
Albert Einstein Medical College
1320)
1322)

MAtch:1322 / 1322 /1950-Albert Einstein Medical College


This Location ALREADY exists:Albert Einstein Medical College
University of Rochester Medical Center
1320)
1322)

MAtch:1322 / 1322 /1950-University of Rochester Medical Center


This Location ALREADY exists:University of Rochester Medical Center
Novant Health Hematology - Forsyth
1320)
1322)

MAtch:1322 / 1322 /1950-Novant Health Hematology - Forsyth


This Location ALREADY exists:Novant Health Hematology – Forsyth
The Ohio State University Wexner Medical Center - James Cancer Hospital
1320)
1322)

MAtch:1322 / 1322 /1950-The Ohio State University Wexner Medical Center - James Cancer Hospital


This Location ALREADY exists:The Ohio State University Wexner Medical Center – James Cancer Hospital
The University of Texas MD Anderson Cancer Center
1320)
1322)

MAtch:1322 / 1322 /1950-The University of Texas MD Anderson Cancer Center


This Location ALREADY exists:The University of Texas MD Anderson Cancer Center
Vseobecna Fakultni nemocnice v Praze
1320)
1322)

MAtch:1322 / 1322 /1950-Vseobecna Fakultni nemocnice v Praze


This Location ALREADY exists:Vseobecna Fakultni nemocnice v Praze
Service d'hématologie clinique CHU de Nice
1320)
1322)

MAtch:1322 / 1322 /1950-Service d'hématologie clinique CHU de Nice


This Location ALREADY exists:Service d’hématologie clinique CHU de Nice
APHP - Sorbonne Universite
1320)
1322)

MAtch:1322 / 1322 /1950-APHP - Sorbonne Universite


This Location ALREADY exists:APHP – Sorbonne Universite
APHP - Hopital Saint Louis
1320)
1322)

MAtch:1322 / 1322 /1950-APHP - Hopital Saint Louis


This Location ALREADY exists:APHP – Hopital Saint Louis
Marien Hospital Dusseldorf; Klinik fur Onkologie und Hamatologie, Palliativmedizin
1320)
1322)

MAtch:1322 / 1322 /1950-Marien Hospital Dusseldorf; Klinik fur Onkologie und Hamatologie, Palliativmedizin


This Location ALREADY exists:Marien Hospital Dusseldorf; Klinik fur Onkologie und Hamatologie, Palliativmedizin
Universitatsklinikum Leipzig; Medizinische Klinik und Poliklinik I
1320)
1322)

MAtch:1322 / 1322 /1950-Universitatsklinikum Leipzig; Medizinische Klinik und Poliklinik I


This Location ALREADY exists:Universitatsklinikum Leipzig; Medizinische Klinik und Poliklinik I
Klinikum rechts der Isar der Technischen Universitat Munchen
1320)
1322)

MAtch:1322 / 1322 /1950-Klinikum rechts der Isar der Technischen Universitat Munchen


This Location ALREADY exists:Klinikum rechts der Isar der Technischen Universitat Munchen
Universitatsklinikum Munster
1320)
1322)

MAtch:1322 / 1322 /1950-Universitatsklinikum Munster


This Location ALREADY exists:Universitatsklinikum Munster
Soroka University MC
1320)
1322)

MAtch:1322 / 1322 /1950-Soroka University MC


This Location ALREADY exists:Soroka University MC
Edith Wolfson Medical Center
1320)
1322)

MAtch:1322 / 1322 /1950-Edith Wolfson Medical Center


This Location ALREADY exists:Edith Wolfson Medical Center
Hadassah University MC
1320)
1322)

MAtch:1322 / 1322 /1950-Hadassah University MC


This Location ALREADY exists:Hadassah University MC
Azienda Ospedaliera Santa Croce e Carle
1320)
1322)

MAtch:1322 / 1322 /1950-Azienda Ospedaliera Santa Croce e Carle


This Location ALREADY exists:Azienda Ospedaliera Santa Croce e Carle
Instituto Romagnolo per lo Studio dei Tumori "Dino Amadori"
1320)
1322)

MAtch:1322 / 1322 /1950-Instituto Romagnolo per lo Studio dei Tumori "Dino Amadori"


This Location ALREADY exists:Instituto Romagnolo per lo Studio dei Tumori "Dino Amadori"
Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz
1320)
1322)

MAtch:1322 / 1322 /1950-Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz


This Location ALREADY exists:Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz
University Hospital in Krakow
1320)
1322)

MAtch:1322 / 1322 /1950-University Hospital in Krakow


This Location ALREADY exists:University Hospital in Krakow
Hospital de la Santa Creu I Sant Pau (Neuvo Hospital)
1320)
1322)

MAtch:1322 / 1322 /1950-Hospital de la Santa Creu I Sant Pau (Neuvo Hospital)


This Location ALREADY exists:Hospital de la Santa Creu I Sant Pau (Neuvo Hospital)
Hospital Universitaro del a Princesa
1320)
1322)

MAtch:1322 / 1322 /1950-Hospital Universitaro del a Princesa


This Location ALREADY exists:Hospital Universitaro del a Princesa
MD Anderson Cancer Center Madrid
1320)
1322)

MAtch:1322 / 1322 /1950-MD Anderson Cancer Center Madrid


This Location ALREADY exists:MD Anderson Cancer Center Madrid
Hospital Universitario Virgen del Rocio
1320)
1322)

MAtch:1322 / 1322 /1950-Hospital Universitario Virgen del Rocio


This Location ALREADY exists:Hospital Universitario Virgen del Rocio1