This is a 2-part, phase 1/2, open-label, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, pharmacogenomics, and efficacy of CYC140 administered orally daily. This study consists of Phase 1 and Phase 2 components in subjects with advanced solid tumors and lymphoma who have progressed despite having standard therapy or for which no standard therapy exists.
Phase 1 part of the study will consist of a dose-escalation and a dose-finding component. Phase 2 will enroll subjects with locally advanced, recurrent, or metastatic, histologically confirmed advanced solid tumors or lymphoma, who have failed all standard therapies or for whom standard therapy does not exist, into 8 groups: Group 1: Bladder cancer Group 2: Breast cancer: Triple-negative breast cancer (TNBC) Group 3: Lung cancer (non-small cell lung cancer \[NSCLC\] and small cell lung cancer \[SCLC\]) Group 4: Hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) Group 5: Metastatic colorectal cancer (mCRC) including KRAS-mutated mCRC Group 6: B-cell lymphoma including diffuse large B-cell lymphoma (DLBCL) Group 7: T-cell lymphoma (cutaneous T-cell lymphoma \[CTCL\] and peripheral T-cell lymphoma \[PTCL\]) Group 8: Basket cohort: tumor types that are suspected to have a related mechanism of action but are not included in previous groups including, esophageal, prostate, ovarian and pancreatic cancers
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
330
CYC140 is a highly selective, orally- and intravenously- available, ATP-competitive inhibitor of PLK1.
City of Hope
Duarte, California, United States
RECRUITINGUPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
Maximum tolerated dose
The incidence rate of dose-limiting toxicities (first cycle only) at each dose level
Time frame: 6 months
Overall Response Rate (ORR)
Assessment of response criteria according to RESIST, Lugano or mSWAT.
Time frame: 18 months
Adverse events
Type, frequency, and severity of adverse drug reactions
Time frame: 24 months
AUC
CYC140 plasma concentrations
Time frame: 6 months
Cmax
CYC140 plasma concentrations
Time frame: 6 months
Tmax
CYC140 plasma concentrations
Time frame: 6 months
T1/2
CYC140 plasma concentrations
Time frame: 6 months
Disease Control Rate
To evaluate the disease control rate (DCR) in subjects receiving CYC140.
Time frame: 24 months
Duration of Response
To evaluate the duration of response (DOR) in subjects receiving CYC140.
Time frame: 24 months
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Seoul National University Hospital
Seoul, South Korea
RECRUITINGHospital Universitario Vall d'Hebron
Barcelona, Spain
RECRUITINGProgression-free Survival
To evaluate progression-free survival (PFS) in subjects receiving CYC140.
Time frame: 24 months
Overall Survival
To evaluate overall survival (OS) in subjects receiving CYC140.
Time frame: 24 months