This is a 2-part, phase I/II, open-label, multicenter study designed to evaluate the safety, PK, PD and preliminary efficacy of TCC1727 tablets administered orally QD.
The study will be divided into two stages: the first stage is a phase I dose finding study in patients with advanced solid tumors; the second stage is a phase II cohort expansion study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
56
TCC1727 tablet will be administered orally once a day (QD) every morning for 3 days followed by discontinuation for 4 days, and 21 days/cycle on an empty stomach.
Drug: TCC1727 tablet TCC1727 tablet will be administered orally twice a day (BID) every morning , and 21 days/cycle on an empty stomach.
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
RECRUITINGPhase I: To determine dose-limiting toxicity (DLT) at each dose level and identify MTD and RP2D.
Phase I: Dose Escalation To observe the tolerability and safety of TCC1727 tablets and determine the maximum-tolerated dose (MTD) and the recommended phase II dose (RP2D) of TCC1727 tablets when administered orally once a day (QD) in 21-day cycle in patients with advanced solid tumors.
Time frame: 21 days
Phase II: To evaluate the preliminary efficacy of TCC1727 tablets as measured by ORR in patients with advanced solid tumors with DNA damage response (DDR) defects
Phase II: Cohort Expansion ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for each tumor type. The overall response rate is defined as proportion of subjects who had the best overall response (BOR) of complete response (CR) or partial response (PR).
Time frame: 6 months
Phase I: Dose Escalation To observe the preliminary efficacy of TCC1727 tablets as measured by overall response rate (ORR) in patients with advanced solid tumors.
To evaluate the preliminary efficacy by objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression free survival (PFS) and overall survival (OS).
Time frame: 6 months
Phase I: To evaluate the pharmacokinetic (PK) of TCC1727 tablets in patients with advanced solid tumors
Phase I: Dose Escalation Pharmacokinetic parameters: Tmax
Time frame: 21 days
Phase I:
Phase I: Dose Escalation Pharmacokinetic parameters: Cmax
Time frame: 21 days
Phase I:
Phase I: Dose Escalation Pharmacokinetic parameters: t1/2
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Time frame: 21 days
Phase I:
Phase I: Dose Escalation Pharmacokinetic parameters: AUC0-t,
Time frame: 21 days
Phase I:
Phase I: Dose Escalation Pharmacokinetic parameters: Cmax,ss
Time frame: 21 days
Phase I:
Phase I: Dose Escalation Pharmacokinetic parameters: AUCtau,ss,
Time frame: 21 days
Phase I:
Phase I: Dose Escalation Pharmacokinetic parameters: Cmin,ss
Time frame: 21 days
Phase II: To evaluate the safety and tolerability of TCC1727 tablets in patients with advanced solid tumors with DDR defects
Phase II: Cohort Expansion Assessment of all AEs, SAEs and TEAEs;
Time frame: 6 months