XZB-0004 is a novel and potent small molecule inhibitor of receptor tyrosine kinase AXL. This is an open-label, multicentre phase I study of XZB-0004 in patients with solid tumors. Part 1 is a dose-escalation study to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic profile of XZB-0004, and then to identify a safe and pharmacologically active dose for evaluation in subsequent cohorts or clinical studies. Part 2 is a study to evaluate the efficacy and safety of XZB-0004 combined with Penpulimab in patients with NSCLC or advanced solid tumors.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
128
Part 1a: 100mg BID, 150mg BID, and 200mg BID of XZB-0004 are planned to be evaluated, and the possibility of exploring higher or lower doses is not ruled out. Continuous administration of XZB-0004 for 21 days is a treatment cycle. Part 1b: XZB-0004 in combination with Penpulimab in subjects with advanced NSCLC or solid tumors, starting at a dose level down from the RP2D of XZB-0004 monotherapy- cohort 1: Advanced or metastatic NSCLC with advanced disease progression after treatment with PD-1 or PD-L1 inhibitors; cohort 2: Advanced or metastatic NSCLC with advanced disease progression after platinum-containing chemotherapy without prior use of any immunocheckpoint inhibitors; cohort3: Advanced or metastatic solid tumors that cannot be radically cured by surgery or local therapy, including but not limited to urothelial carcinoma, melanoma, etc. Subjects had disease progression since last antitumor therapy, no availability or intolerance or refusal of standard therapy.
Shanghai Pulmonary Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGMaximum tolerated dose (MTD) (for Part 1a)
Determine MTD of XZB-0004
Time frame: Up to 3 weeks
Recommended phase 2 dose (RP2D)(for Part 1a)
Determine RP2D of XZB-0004
Time frame: Up to 3 weeks
Overall Response Rate (ORR) (for Part 1b)
Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: Up to 2-3 years
Pharmakinetic parameter - AUC0-t (for Part 1a and Part 1b)
To determine AUC0-t of XZB-0004
Time frame: Up to 63 days
Pharmakinetic parameter - AUC0-∞ (for Part 1a and Part 1b)
To determine AUC0-∞ of XZB-0004
Time frame: Up to 63 days
Pharmakinetic parameter - Cmax (for Part 1a and Part 1b)
To determine Cmax of XZB-0004
Time frame: Up to 63 days
Pharmakinetic parameter - Tmax (for Part 1a and Part 1b)
To determine Tmax of XZB-0004
Time frame: Up to 63 days
Pharmakinetic parameter - t½ (for Part 1a and Part 1b)
To determine t½ of XZB-0004
Time frame: Up to 63 days
Pharmakinetic parameter - CL/F (for Part 1a and Part 1b)
To determine CL/F of XZB-0004
Time frame: Up to 63 days
Pharmakinetic parameter - Vz/F (for Part 1a and Part 1b)
To determine Vz/F of XZB-0004
Time frame: Up to 63 days
Overall Response Rate (ORR) (for Part 1a)
Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: Up to 2-3 years
Progression free survival (PFS) (for Part 1a and Part 1b)
PFS is defined as the time from the date of first dose of XZB-0004 till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).
Time frame: Up to 2-3 years
Duration of response (DOR) (for Part 1a and Part 1b)
DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.
Time frame: Up to 2-3 years
Disease control rate (DCR) (for Part 1a and Part 1b)
DCR is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1.
Time frame: Up to 2-3 years
Overall survival (OS) (for Part 1a and Part 1b)
OS is the time from the date of first dose of XZB-0004 to death due to any cause.
Time frame: Up to 2-3 years
Incidence and severity of adverse events (AEs)(for Part 1b)
An adverse event (AE) is any untoward medical occurrence or the deterioration of existing medical event in a clinical study subject administered an investigational drug, which does not necessarily have an unequivocal causal relationship with the investigational product.
Time frame: Up to 2-3 years
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