A Study of XZB-0004 in Patients With Solid Tumors

Official title

A Phase I, Open-label, Dose-escalation Study of the Safety, Pharmacokinetics and Efficacy of the XZB-0004 in Patients With Solid Tumours

Overview

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.

Interventions

• Drug XZB-0004
  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

Primary outcome measures

• Maximum tolerated dose (MTD) (for Part 1a) [Time frame: Up to 3 weeks]
• Recommended phase 2 dose (RP2D）(for Part 1a) [Time frame: Up to 3 weeks]
• Overall Response Rate (ORR) (for Part 1b) [Time frame: Up to 2-3 years]

Secondary outcome measures (12)

• Pharmakinetic parameter - AUC0-t (for Part 1a and Part 1b) [Time frame: Up to 63 days]
• Pharmakinetic parameter - AUC0-∞ (for Part 1a and Part 1b) [Time frame: Up to 63 days]
• Pharmakinetic parameter - Cmax (for Part 1a and Part 1b) [Time frame: Up to 63 days]
• Pharmakinetic parameter - Tmax (for Part 1a and Part 1b) [Time frame: Up to 63 days]
• Pharmakinetic parameter - t½ (for Part 1a and Part 1b) [Time frame: Up to 63 days]
• Pharmakinetic parameter - CL/F (for Part 1a and Part 1b) [Time frame: Up to 63 days]
• Pharmakinetic parameter - Vz/F (for Part 1a and Part 1b) [Time frame: Up to 63 days]
• Overall Response Rate (ORR) (for Part 1a) [Time frame: Up to 2-3 years]
• Progression free survival (PFS) (for Part 1a and Part 1b) [Time frame: Up to 2-3 years]
• Duration of response (DOR) (for Part 1a and Part 1b) [Time frame: Up to 2-3 years]
• Disease control rate (DCR) (for Part 1a and Part 1b) [Time frame: Up to 2-3 years]
• Overall survival (OS) (for Part 1a and Part 1b) [Time frame: Up to 2-3 years]

Eligibility criteria

Inclusion criteria

• Patient has signed informed consent before any trial related activities.
• Be 18 years of age or older and less than 75 years at the time of signing the informed consent.
• Part 1: Have a histologically or cytologically confirmed diagnosis of a solid tumour malignancy; Part 2：Have a histologically or cytologically confirmed diagnosis of a NSCLC or solid tumour malignancy.
• Have evaluable (for Part 1) or measurable (for Part 2) disease as the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
• Have a performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
• Have adequate organ function.
• Have recovered to ≤ grade 1 or Meet the requirements of the study from the effects of any prior cancer therapy, except for alopecia; irreversible neuropathy should have recovered to ≤ grade 2.
• Have a life expectancy greater than 3 months.
• Eligible patients (male and female) who are fertile must agree to at least use a reliable contraceptive method with partner.
• Willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion criteria

• Previous use of AXL inhibitors and immunotherapy was consistent with protocol requirements.
• Received anti-tumor therapy such as chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy or other therapy within 4 weeks prior to the first dose of the investigational drug.
• Received other unmarketed investigational drugs or treatments within 4 weeks or 5 times the elimination half-life prior to the first dose of the investigational drug.
• Treatment with systemic glucocorticoids (prednisone > 10mg per day or equivalent) or other immunosuppressive agents within 14 days before the first dose of a trial drug.
• Inability to swallow, intestinal obstruction or other factors that affect the taking and absorption of the drug.
• Patient with heart function impaired or clinically significant heart disease.
• Any condition or illness that, in the opinion of the Investigator, would interfere with the evaluation of the safety of the study drug.
• History of immune deficiencies, including positive HIV antibody tests.
• Patient is in the active stage of HBV or HCV.
• History of solid organ transplant or bone marrow transplant.
• Any other malignant tumor has been diagnosed within 5 years.
• Has known Primary tumor of the central nervous system or central nervous system metastase.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage were present within 4 weeks before the first dose of the trial drug.
• Subjects with psychiatric disorders that may affect trial compliance.
• history of Alcoholism or drug abuse.
• Pregnant or breastfeeding.
• The researchers considered that there were some cases that were not suitable for inclusion.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Pulmonary Hospital — Shanghai

Identifiers

NCT: NCT05772455 · XZB-0004-1001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗