A Study of XZB-0004 in Patients With Solid Tumors

• ClinicalTrials.gov Identifier: NCT05772455
• Recruitment Status: Not yet recruiting
• Last Update Posted: March 16, 2023
• Sponsor: Xuanzhu Biopharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Xuanzhu Biopharmaceutical Co., Ltd.

Study Description

Brief Summary:

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 Peamplimab in patients with NSCLC or advanced solid tumors.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor; NSCLC	Drug: XZB-0004	Phase 1

Study Design

• Study Type: Interventional
• Estimated Enrollment: 128 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: April 2023
• Estimated Primary Completion Date: June 2025
• Estimated Study Completion Date: February 2027

Arms and Interventions

Arm

Intervention/treatment

Experimental: XZB-0004

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 peramprizumab 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.

Outcome Measures

Primary Outcome Measures :

1. Maximum tolerated dose (MTD) (for Part 1a) [ Time Frame: Up to 3 weeks ]
   Determine MTD of XZB-0004
2. Recommended phase 2 dose (RP2D）(for Part 1a) [ Time Frame: Up to 3 weeks ]
   Determine RP2D of XZB-0004
3. Overall Response Rate (ORR) (for Part 1b) [ Time Frame: Up to 2-3 years ]
   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

Secondary Outcome Measures :

1. Pharmakinetic parameter - AUC0-t (for Part 1a and Part 1b) [ Time Frame: Up to 63 days ]
   To determine AUC0-t of XZB-0004
2. Pharmakinetic parameter - AUC0-∞ (for Part 1a and Part 1b) [ Time Frame: Up to 63 days ]
   To determine AUC0-∞ of XZB-0004
3. Pharmakinetic parameter - Cmax (for Part 1a and Part 1b) [ Time Frame: Up to 63 days ]
   To determine Cmax of XZB-0004
4. Pharmakinetic parameter - Tmax (for Part 1a and Part 1b) [ Time Frame: Up to 63 days ]
   To determine Tmax of XZB-0004
5. Pharmakinetic parameter - t½ (for Part 1a and Part 1b) [ Time Frame: Up to 63 days ]
   To determine t½ of XZB-0004
6. Pharmakinetic parameter - CL/F (for Part 1a and Part 1b) [ Time Frame: Up to 63 days ]
   To determine CL/F of XZB-0004
7. Pharmakinetic parameter - Vz/F (for Part 1a and Part 1b) [ Time Frame: Up to 63 days ]
   To determine Vz/F of XZB-0004
8. Overall Response Rate (ORR) (for Part 1a) [ Time Frame: Up to 2-3 years ]
   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
9. Progression free survival (PFS) (for Part 1a and Part 1b) [ Time Frame: Up to 2-3 years ]
   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).
10. Duration of response (DOR) (for Part 1a and Part 1b) [ Time Frame: Up to 2-3 years ]
    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.
11. Disease control rate (DCR) (for Part 1a and Part 1b) [ Time Frame: Up to 2-3 years ]
    DCR is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1.
12. Overall survival (OS) (for Part 1a and Part 1b) [ Time Frame: Up to 2-3 years ]
    OS is the time from the date of first dose of XZB-0004 to death due to any cause.
13. Incidence and severity of adverse events (AEs)(for Part 1b) [ Time Frame: Up to 2-3 years ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient has signed informed consent before any trial related activities.
2. Be 18 years of age or older and less than 75 years at the time of signing the informed consent.
3. 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.
4. Have evaluable (for Part 1) or measurable (for Part 2) disease as the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
5. Have a performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
6. Have adequate organ function.
7. 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.
8. Have a life expectancy greater than 3 months.
9. Eligible patients (male and female) who are fertile must agree to at least use a reliable contraceptive method with partner.
10. Willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Previous use of AXL inhibitors and immunotherapy was consistent with protocol requirements.
2. 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.
3. 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.
4. 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.
5. Inability to swallow, intestinal obstruction or other factors that affect the taking and absorption of the drug.
6. Patient with heart function impaired or clinically significant heart disease.
7. Any condition or illness that, in the opinion of the Investigator, would interfere with the evaluation of the safety of the study drug.
8. History of immune deficiencies, including positive HIV antibody tests.
9. Patient is in the active stage of HBV or HCV.
10. History of solid organ transplant or bone marrow transplant.
11. Any other malignant tumor has been diagnosed within 5 years.
12. Has known Primary tumor of the central nervous system or central nervous system metastase.
13. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage were present within 4 weeks before the first dose of the trial drug.
14. Subjects with psychiatric disorders that may affect trial compliance.
15. history of Alcoholism or drug abuse.
16. Pregnant or breastfeeding.
17. The researchers considered that there were some cases that were not suitable for inclusion.

Contacts and Locations

Contacts

Contact: Xiujie Zhang; +86-13671737230; zhangxiujie@xuanzhubio.com

Locations

China, Shanghai

Shanghai Pulmonary Hospital

Shanghai, Shanghai, China, 200433

Contact: Caicun Zhou +86-13301825532 caicunzhoudr@163.com

Sponsors and Collaborators

Xuanzhu Biopharmaceutical Co., Ltd.

More Information

• Responsible Party: Xuanzhu Biopharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT05772455
• Other Study ID Numbers: XZB-0004-1001
• First Posted: March 16, 2023
• Last Update Posted: March 16, 2023
• Last Verified: March 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xuanzhu Biopharmaceutical Co., Ltd.:

XZB-0004; AXL inhibitor

Additional relevant MeSH terms:

Neoplasms