CX1003 is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit vascular endothelial growth factor receptor 2 (VEGFR2) and hepatocyte growth factor receptor (HGFR/MET). This study aimed to evaluate the safety, pharmacokinetics, and antitumor activity of CX1003 in patients with refractory advanced or metastatic solid tumors.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
126
Oral dose A 4-day single dose period, followed by a period of daily-dose in continuous 28-day treatment cycle (the 1st cycle) or 21-day treatment cycles (the 2nd cycle and beyond) Dosage range: 25 mg, 50mg, 75mg, 100mg,125mg,150mg,175mg
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality, China
RECRUITINGIncidence of dose-limiting toxicities (DLTs) by NCI CTCAE 5.0: Dose Escalation Stage
Occurrence of any of the following toxicities was considered DLT if judged by the Investigator to be possibly, probably, or definitely related to the administration of CX1003: * Any Grade 3 or higher non-hematologic toxicity (including persisting nausea, vomiting, diarrhea, and electrolyte imbalances despite optimal medical management); * Grade 4 neutropenia for \>5 consecutive days; * Grade 3 or higher febrile neutropenia; * Grade 3 or higher neutropenia associated with infection; * Grade 4 thrombocytopenia; * Grade 3 or higher thrombocytopenia with clinically significant bleeding or that requires a platelet transfusion.
Time frame: First 5 weeks after initial administration of CX1003
Maximum tolerated dose (MTD): Dose Escalation Stage
The maximum tolerated dose (MTD) was defined as the highest dose for a given schedule that was expected to cause DLTs in no more than 33% of patients.
Time frame: First 5 weeks after initial administration of CX1003
Pharmacokinetics (PK) profile: Cmax
Parameters: Peak Plasma Concentration (Cmax)
Time frame: First 5 weeks after initial administration of CX1003
Pharmacokinetics (PK) profile: Tmax
Parameters: Time to reach the maximum plasma concentration (Tmax)
Time frame: First 5 weeks after initial administration of CX1003
Pharmacokinetics (PK) profile: T1/2
Parameters: Terminal half-life (T1/2)
Time frame: First 5 weeks after initial administration of CX1003
Pharmacokinetics (PK) profile: AUC
Parameters: Area under the plasma concentration versus time curve (AUC)
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Time frame: First 5 weeks after initial administration of CX1003
Pharmacokinetics (PK) profile: CL/F
Parameters: Apparent body clearence from plasma (CL/F)
Time frame: First 5 weeks after initial administration of CX1003
Pharmacokinetics (PK) profile: Vz/F
Parameters: Apparent volume of distribution (Vz/F)
Time frame: First 5 weeks after initial administration of CX1003
Objective Response Rate (ORR)
Overall response rate (ORR) was defined as the percentage of participants with a best overall complete response (CR) or partial response (PR) per RECIST 1.1.
Time frame: up to 24 months
Progression-free survival (PFS)
Progression-free survival (PFS) was defined as the time from the start date of study drug to the date of the first radiologically documented progressive disease (PD) per RECIST 1.1 or death due to any cause.
Time frame: up to 24 months
Disease Control Rate (DCR)
Disease Control Rate (DCR) was defined as the percentage of participants with a best overall complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1.
Time frame: up to 24 months
Duration of Response (DOR)
Duration of response (DOR) was defined as the time from first documented response (partial response (PR) or complete response (CR)) to the date of first documented disease progression (PD) or death due to any cause, among patients with a confirmed PR or CR per RECIST 1.1.
Time frame: up to 24 months
Safety profile as assessed by the incidence, duration, and severity of adverse events
Incidence, duration, and severity of AEs measured by laboratory assessments and physical findings according to NCI CTCAE 5.0.
Time frame: From first dose of CX1003 to 30 days after last dose