SHS_492456 PAGJ CCRS 18225
Phase 1/2 Open Label, Multi-center, Dose-Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered Fimepinostat (CUDC-907), a PI3K and HDAC Inhibitor, in Subjects With Refractory or Relapsed Lymphoma
Subjects of ≥ 18 years of age with any of the following:
For Dose-Escalation cohorts:
Fimepinostat + venetoclax: Histopathologically confirmed DLBCL or HGBL that is refractory to, or has relapsed after, treatment with at least 1 prior regimen
Fimepinostat + rituximab + bendamustine: Histopathologically confirmed diagnosis of lymphoma (i.e., B-cell non-Hodgkin lymphoma [NHL], TCL, or HL) that is refractory to, or has relapsed after, treatment with at least 1 prior regimen.
For Dose-Expansion cohorts:
Fimepinostat + venetoclax: R/R DLBCL or HGBL with both MYC and BCL2 alterations and/or overexpression (DHL, THL, or DEL) that is refractory to, or has relapsed after, 1 or more prior lines of therapy.
Fimepinostat + rituximab + bendamustine: R/R DLBCL or HGBL that is refractory to, or has relapsed after, 1 or more prior lines of therapy
Measurable disease by CT or PET/CT. MRI acceptable as per protocol.• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Recovery to Grade 1 or baseline of any toxicity due to prior systemic treatments (excluding alopecia).
Absolute neutrophil count ≥ 1,000/µL; platelets ≥ 75,000/µL for patients with no bone marrow involvement by malignancy; platelets ≥ 50,000/µL for patients with bone marrow involvement by malignancy.
Creatinine ≤ 1.5x upper limit of normal (ULN); total bilirubin ≤ 1.5x ULN; AST/ALT ≤ 2.5x ULN.
Life expectancy of at least 3 months.
Intention to undergo stem cell transplant or treatment with chimeric antigen receptor (CAR) T-cell therapy.
Systemic anti-cancer therapy or investigational agent within 3 weeks of study entry, except for nitrosoureas or mitomycin C (6 weeks).
Other non-cytotoxic anti-cancer therapy or investigational agent within 5 half-lives or 21 days prior to study treatment, whichever is shorter, as long as any drug related toxicities have resolved to Grade 1 or less. Dexamethasone up to 12 mg/d is allowed as supportive therapy and does not exclude participation.
Graft vs. host disease following prior allogeneic transplant within 3 months prior to study treatment.
Ongoing treatment with chronic immunosuppressants.
Active CNS lymphoma.
Known gastrointestinal condition that would interfere with swallowing or the oral absorption or tolerance of fimepinostat.
Serious infection requiring systemic antibiotic therapy within 14 days prior to study treatment.
Uncontrolled or severe cardiovascular disease
Unstable or clinically significant concurrent medical condition.
Second primary malignancy within 2 years of study entry other than what is specified in the protocol.
Known HIV positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
Active CMV infection, presence of CMV antigenemia, or evidence of any invasive CMV end organ disease (e.g., CMV colitis).
Krish Patel, M.D.