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
Male or female subjects aged ≥18 years old;
Phase I dose escalation period: Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor, assessed by investigator that no standard therapy exists, or the tumor has relapsed, progressed or was nonresponsive to available therapies, or intolerance, or not suitable to standard therapy at current stage. Priority will be given to patients who have previously documented NTRK or ROS1 gene fusion confirmed by the central laboratory; Phase I dose expansion and Phase II: Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor, patients can provide a written report of pathological diagnosis of NTRK or ROS1 positive tested by qualified laboratory;
Phase I dose expansion cohort 1 and Phase II cohort 1: locally advanced, or metastatic solid tumor with NTRK gene fusion Phase I dose expansion cohort 2 and Phase II cohort 2： locally advanced, or metastatic NSCLC with ROS1 gene fusion that has progressed to crizotinib and other therapies or was intolerance to crizotinib Phase I dose expansion cohort 3: locally advanced, or metastatic NSCLC with ROS1 gene fusion who have not previously received crizotinib or other therapy.
phase I dose escalation: at least 1 measurable target lesion according to RECIST version 1.1 Phase I dose expansion and Phase II: at least 1 measurable target lesion according to RECIST version 1.1 (Tumor lesions treated with prior radiation or other local treatment are considered measurable if they show definite progression)
Received other unmarketed investigational drugs or treatments within 4 weeks prior to the first dose of the investigational drug;
Major organ surgery (except biopsy) or significant trauma within 4 weeks prior to first dose of the investigational drug or required elective surgery during the trial;
Adverse reactions to previous antitumor therapy have not recovered to NCI CTCAE 5.0 ≤ grade 1 (except for alopecia, grade 2 peripheral neurotoxicity, stable hypothyroidism after hormone replacement therapy, etc.);
Inability to swallow drug, or a condition that the investigator judged to severely affect gastrointestinal absorption (eg:Chronic Diarrhea, intestinal obstruction, etc.);
Single group
XZP-5955 tablets
DrugPhase 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
Maximum tolerated dose (MTD) (Phase I dose escalation)
Determine MTD of XZP-5955
Number of patients with adverse events (Phase I dose escalation)
Incidence of AE as assessed by CTCAE 5.0
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
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
Phase I: Maximum plasma concentration (Cmax) of XZP-5955
To determine the maximum plasma concentration (Cmax) of XZP-5955
Phase I: Oral clearance (CL/F) of XZP-5955
To determine the oral clearance (CL/F) of XZP-5955
objective response rate (ORR) (Phase I and Phase II)
To determine the preliminary objective response rate (ORR) by investigator
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