This is an open phase I/Ib clinical study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and initial efficacy of RP903 in patients with advanced malignancies who have failed standard treatment or have no standard treatment options. The study was divided into two parts: dose escalation and dose extension (Phase Ia) and clinical extension (Phase Ib).
Phase Ia is divided into two phases of dose escalation and dose extension: This part includes dose escalation and dose extension of RP903 single agent to investigate the safety, tolerability, maximum tolerated dose and pharmacokinetic (PK) characteristics of RP903 single agent. Phase Ib is the clinical indication expansion phase, and the primary purpose of this phase is to evaluate the initial safety and anti-tumor efficacy in a selected indication target population. After determining RP903 monotherapy RP2D in Phase Ia, SMC will select four advanced malignant tumors with PIK3CA mutations (cervical cancer, endometrial cancer, breast cancer, and ovarian cancer) as indications for clinical expansion studies based on phase Ia efficacy, safety, and pharmacokinetic (PK) data. The dose was determined according to the results of the dose escalation phase and the dose extension phase.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
69
Ia:RP903 50mg, 100mg, 200mg, 300mg,350mg,or other dose, po qd for each 28-day cycle; Ib: RP903,RP2D,po qd for each 28-day cycle
Beijing Cancer Hospital
Beijing, China
The First Affiliated Hospital of Bengbu Medical College
Bengbu, China
Jilin Cancer Hospital
Changchun, China
Jilin University First Hospital
Changchun, China
Sichuan Cancer Hospital
Chengdu, China
Chongqing University Cancer Hospital
Chongqing, China
Fujian Cancer Hospital
Fuzhou, China
Fujian Medical University Union Hospital
Fuzhou, China
Sir Run Run Shaw Hospital
Hangzhou, China
Zhejiang Cancer Hospital
Hangzhou, China
...and 13 more locations
Ia:dose-limiting toxicity(DLTs)
Incidence and severity of dose-limiting toxicity (DLTs)
Time frame: 28 days
Ia:Adverse Events
Incidence and severity of Adverse Events(AEs) according to NCI-CTCAE
Time frame: 2 years
Ia: serious adverse events
Incidence and severity of serious adverse events(SAEs) according to NCI-CTCAE
Time frame: 2 years
Ia: Abnormal changes in Laboratory test and other abnormalities
Incidence and severity of abnormal changes in Laboratory test and other tests with clinically significant according to NCI-CTCAE
Time frame: 2 years
Ia: MTD
Maximum Tolerated Dose(MTD)
Time frame: 2 years
Ia: MAD
Maximum Administrated Dose(MAD)
Time frame: 2 years
Ia:RP2D
Recommended Phase II Dose(RP2D)
Time frame: 2 years
Ib:objective response rate(ORR);
Efficacy evaluated by the investigator according to RECIST v1.1: objective response rate (ORR);
Time frame: 2 years
Ib:AE
Type, frequency, duration, severity and characteristics of Adverse Events (AEs) according to NCI-CTCAE
Time frame: 2 years
Ib:SAE
Type, frequency, duration, severity and characteristics of serious adverse events(SAEs) according to NCI-CTCAE
Time frame: 2 years
Ia:the concentration of RP903 or its metabolites (if applicable)
the concentration of RP903 or its metabolites (if applicable) in individual subjects at different time points after administration;
Time frame: 1 years
Ia:Cmax
peak concentration
Time frame: 1 years
Ia:Ctrough
trough concentration
Time frame: 1 years
Ia:Tmax
time to peak
Time frame: 1 years
Ia:AUC0-t and AUC0-∞
area under the plasma drug concentration-time curve
Time frame: 1 years
Ia:Vd/F
distribution volume
Time frame: 1 years
Ia:CL/F
clearance
Time frame: 1 years
Ia:t1/2
half-life
Time frame: 1 years
Ia:Rac
cumulative factor
Time frame: 1 years
Ia:ORR
objective response rate
Time frame: 1 years
Ia:DoR
duration of response
Time frame: 1 years
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Ia:DCR
disease control rate
Time frame: 1 years
Ia:TTR
time to response
Time frame: 1 years
Ia:PFS
progression-free survival
Time frame: 1 years
Ia:OS
overall survival
Time frame: 1 years
Ib:safety:AE
Type, frequency, duration, severity and characteristics of serious adverse events(SAEs) according to NCI-CTCAE
Time frame: 2 years
Ib:safety:SAE
Type, frequency, duration, severity and characteristics of serious adverse events(SAEs) according to NCI-CTCAE
Time frame: 2 years
Ib:safety:Body temperature
Body temperature changes according to NCI-CTCAE
Time frame: 2 years
Ib:safety:pulse
pulse changes according to NCI-CTCAE
Time frame: 2 years
Ib:safety:respiratory rate
respiratory rate changes according to NCI-CTCAE
Time frame: 2 years
Ib:safety: blood pressure
blood pressure changes according to NCI-CTCAE
Time frame: 2 years
Ib:safety:laboratory test
laboratory test changes according to NCI-CTCAE
Time frame: 2 years
Ib:safety:heart rate
heart rate changes according to NCI-CTCAE
Time frame: 2 years
Ib:safety:QT
QT changes according to NCI-CTCAE
Time frame: 2 years
Ib:safety:QTcF
QTcF changes according to NCI-CTCAE
Time frame: 2 years
Ib:safety:PR
PR changes according to NCI-CTCAE
Time frame: 2 years
Ib:DoR
duration of response
Time frame: 1 years
Ib:DCR
disease control rate
Time frame: 1 years
Ib:TTR
time to response
Time frame: 1 years
Ib:PFS
progression-free survival
Time frame: 1 years
Ib:OS
overall survival
Time frame: 2 years
Ib:Concentrations of RP903 or its metabolites
Concentrations of RP903 or its metabolites (if applicable) in individual subjects at different time points after dosing.
Time frame: 1 years