The purpose of this first-in-human (FiH) study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of CKD-512 given alone and in combination with pembrolizumab in subjects with advanced or metastatic solid tumors who have failed all standard available therapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Orally administered BID
Intravenous (IV) Infusion
Severance Hospital, Yonsei University Health System
Seoul, South Korea
RECRUITINGPart A: Maximum tolerated dose (MTD) or Optimal biologically effective dose (OBED)
Number and proportion of subjects who experience at least 1 DLT based on incidence, nature, and severity of TEAEs and SAEs graded according to NCI-CTCAE version 5.0 as well as on changes from baseline assessments.
Time frame: Up to 2 years
Part B: Recommended dose for expansion (RDE)
Number and proportion of subjects who experience at least 1 DLT based on incidence, nature, and severity of TEAEs and SAEs graded according to NCI-CTCAE version 5.0 as well as on changes from baseline assessments.
Time frame: Up to 2 years
Safety and tolerability
Incidence and severity of TEAEs, incidence of SAEs and TRAEs etc. according to the NCI-CTCAE version 5.0
Time frame: Up to 2 years
Maximum Observed Plasma Concentration (Cmax)
Cmax is defined as the maximum observed plasma concentration of CKD-512
Time frame: Up to 2 years
Cmax at steady state (Cmax_ss)
Cmax\_ss is defined as the maximum observed plasma concentration of CKD-512 at steady state
Time frame: Up to 2 years
Area Under the Curve to the last measurable concentration (AUClast)
AUClast is defined as the area under the plasma concentration-time curve of CKD-512 from the time of dosing to the time of the last measurable concentration.
Time frame: Up to 2 years
Area Under the Curve over the dosing interval tau (AUCtau)
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AUCtau is defined as the area under the plasma concentration-time curve of CKD-512 over a dosing interval (tau), usually at steady state.
Time frame: Up to 2 years
Overall Response Rate (ORR)
ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR), assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: Up to 2 years
Duration of Response (DOR)
DOR is defined as the time from the date of the first documented objective tumor response (CR or PR) assessed according to RECIST or iRECIST criteria, until the date of the first documented disease progression or death from any cause, whichever occurs first.
Time frame: Up to 2 years
Disease Control Rate (DCR)
DCR is defined as the percentage of participants whose best overall response is CR, PR, or stable disease (SD), assessed according to RECIST version 1.1 or iRECIST criteria.
Time frame: Up to 2 years
Progression-Free Survival (PFS)
PFS is defined as the time from the date of treatment initiation to the date of the first documented disease progression or death from any cause, whichever occurs first, assessed according to RECIST version 1.1 or iRECIST criteria.
Time frame: Up to 2 years