A phase I/II study to examine the safety, tolerability, pharmacokinetics and efficacy of XZP-5955 tablets in patients with advanced solid tumors harboring NTRK or ROS1 gene fusion
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
360
Phase I dose escalation: For each dose cohort, XZP-5955 tablet will be administered orally, single dose for day 1 and then from day 4, administered for continuous cycles of 21 consecutive days for each cycle Phase I dose expansion: XZP-5955 tablet will be administered orally, once daily for continuous cycles of 21 consecutive days for each cycle. Some patients for PK sample collection, the drug will be administered single dose for day 1, then from day 4, administered for continuous cycles of 21 consecutive days for each cycle Phase II: XZP-5955 tablet will be administered orally, once daily for continuous cycles of 21 consecutive days for each cycle
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
RECRUITINGMaximum tolerated dose (MTD) (Phase I dose escalation)
Determine MTD of XZP-5955
Time frame: 24days following first dose of XZP-5955
Number of patients with adverse events (Phase I dose escalation)
Incidence of AE as assessed by CTCAE 5.0
Time frame: within 30 days from last dose
Overall Response Rate (ORR) by Blinded Independent Central Review (BICR) (Phase I dose expansion and phase II)
Per RECIST v1.1 as assessed by BICR
Time frame: 2 to 3 years after first dose of XZP-5955
Phase I: Area under the concentration versus time curve of XZP-5955 in plasma (AUC)
To determine the area under the plasma concentration time curve (AUC) of XZP-5955
Time frame: Pre-dose, up to 72h after drug on Day 1;pre-dose on day 8, day 15 of cycle 1, , pre-dose and up to 12h after drug on day21 of cycle 1;pre-dose on day1 of cycle 2 and 3
Phase I: Maximum plasma concentration (Cmax) of XZP-5955
To determine the maximum plasma concentration (Cmax) of XZP-5955
Time frame: Up to 72 hours post dose of Day 1
Phase I: Oral clearance (CL/F) of XZP-5955
To determine the oral clearance (CL/F) of XZP-5955
Time frame: Pre-dose, up to 72h after drug on Day 1;pre-dose on day 8, day 15 of cycle 1, pre-dose and up to 12h after drug on day21 of cycle 1;pre-dose on day1 of cycle 2 and 3
objective response rate (ORR) (Phase I and Phase II)
To determine the preliminary objective response rate (ORR) by investigator
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Time frame: 2 to 3 years after first dose of XZP-5955
Progression free survival (PFS) (Phase I and Phase II)
To determine the PFS by BICR and investigator
Time frame: 2 to 3 years after first dose of XZP-5955
Duration of response (DOR) (Phase I and Phase II)
To determine the DOR by BICR and investigator
Time frame: 2 to 3 years after first dose of XZP-5955
Disease control rate (DCR) (Phase I and Phase II)
To determine the DOR by BICR and investigator
Time frame: 2 to 3 years after first dose of XZP-5955
Clinical benefit rate (CBR) (Phase I and Phase II)
To determine the CBR by BICR and investigator
Time frame: 2 to 3 years after first dose of XZP-5955
Time to response (TTR) (Phase I and Phase II)
To determine the TTR by BICR and investigator
Time frame: 2 to 3 years after first dose of XZP-5955
Death of response (DpR) (Phase I and Phase II)
To determine the DpR by BICR and investigator
Time frame: 2 to 3 years after first dose of XZP-5955
Overall survival (OS) (Phase I expansion period and Phase II)
To determine the OS
Time frame: 2 to 3 years after first dose of XZP-5955
Intracranial objective response rate (Phase I expansion period and Phase II)
2 to 3 years after first dose of XZP-5955
Time frame: To determine the intracranial ORR
Number of patients with adverse events ((Phase I dose expansion and Phase II)
Incidence of AE as assessed by CTCAE 5.0
Time frame: within 30 days from last dose
Pop PK of XZP-5955 and its metabolite (Phase II)
To determine the PopPK characteristics of XZP-5955
Time frame: pre-dose, Tmax on Day1, pre-dose on day 8 of cycle 1, pre-dose on day 1 of Cycle 2, Tmax,ss on Day 1 of cycle 2, pre-dose on day 1 of cycle 3