Locally Advanced or Metastatic Malignant Solid Tumors
Conditions
Brief summary
This study was an open, multicenter Phase I/II clinical study of WJ05129 in patients with locally advanced or metastatic malignant solid tumors in China, which was divided into three stages: Single-dose escalation,Combined dose extension and efficacy extension. The study included screening, treatment and follow-up periods. The starting dose of this dose-escalation study was set at 2.5 mg/day. Five dose levels were preset.A more flexible BOIN dose escalation method was adopted. The maximum tolerated dose observation period was the first treatment cycle of single administration and multiple consecutive administrations (a total of 2 days) + 21 days = 23 days; In this stage, the two dosage levels of the injectable WJ05129 (RP2D dosage and the lower dose before RP2D) will be selected as the escalating doses for the combined use of WJ05129. The BOIN design will be adopted for dose escalation. Paclitaxel 80mg/m2 will be intravenously infused on days 1, 8, and 15. A 28-day cycle will be used, with the first cycle being the DLT observation period.Efficacy expansion phase: It is preliminarily planned to expand three cohorts of Rb negative TNBC and SCLC andOther solid tumors（Such as gastric and esophageal adenomas, gynecological tumors, etc.）, and recruit about 20-40 people in each cohort.
Interventions
DRUGWJ05129
Twice daily (except for single dose), 12 hours apart, fixed time is recommended
DRUGPaclitaxel injection
80mg/m2 (The maximum dose is 80mg/m2 , and the dose can be adjusted according to the actual situation), The medication is administered on days 1, 8, and 15, and a 28-day period constitutes one cycle.
Sponsors
Sponsor GmbH
Suzhou Junjing BioSciences Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (Open Label)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Willing to participate in the clinical trial of this drug, able to understand and sign informed consent, willing and able to comply with the planned visit and study procedures; 2. Age ≥18 to 75 years old, male and female; 3. Locally advanced (except for patients who can be treated with radical therapy) or metastatic malignant solid tumors confirmed by histology or cytology; 4. The single-dose escalation phase requires patients who have failed standard treatment, are intolerant to standard treatment, or have no standard treatment options；The combined dose escalation phase and the efficacy expansion phase require no treatment with taxane drugs for metastatic diseases, with no more than 4 lines of treatment, and meet one of the following conditions: 1. SCLC: After receiving a platinum-based standard chemotherapy regimen for first-line treatment, whether in localized stage (LS) or extensive stage (ES), there has been progression; 2. TNBC: After receiving first-line standard treatment, previous adjuvant taxane treatment is allowed, provided that the disease-free interval from (new) adjuvant chemotherapy to the development of metastatic disease is ≥ 1 year; 3. Other solid tumors: After receiving the first-line standard treatment recommended by CSCO or NCCN guidelines; 5. Eastern Cooperative Oncology Group (ECOG) Physical status score (Annex 2) 0 to 1; 6. Expected survival ≥ 12 weeks; 7. According to the Response evaluation criteria in solid Tumors (RECIST) 1.1 (Annex 4), there is at least one measurable lesion（Applicable only to the dose escalation and efficacy expansion phases of the combination treatment.）; 8. Voluntarily and informed consent to provide fresh biopsy samples before treatment. For patients unable to provide fresh biopsy samples before treatment, archived samples within 2 years can be provided (dose escalation stage is optional, dose expansion and efficacy expansion stage is mandatory); 9. Have sufficient important organ functions, and meet the following standards in laboratory examination ≤ 7 days before the first drug administration: A: Blood system (transfusion and cytokine support therapy are not allowed within 14 days prior to initial administration) : * Hemoglobin ≥ 90 g/L; * Platelet count ≥ 100×109/L; * Absolute neutrophil count ≥ 1.5×109/L B: Kidney function: * Serum albumin ≥30g/L. (Albumin infusion is not allowed within 14 days before administration) * Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 2.5 × Upper limit of normal (ULN); If liver metastasis occurred, AST/ALT ≤ 5 × ULN; * Serum total bilirubin ≤ 1.5 × ULN; TBIL≤3×ULN in patients with liver metastasis or Gilbert syndrome; * Serum creatinine (Cr) ≤1.5 TIMES ULN or creatinine clearance (calculated using the Cockcroft and Gault formula \[Appendix 1\]) ≥ 50 mL/min; C: Coagulation function: International standardized ratio (INR), prothrombin time (PT) and activated partial thrombin time (aPTT) ≤ 1.5ULN for patients who did not receive anticoagulant therapy; For those receiving anticoagulant therapy (e.g., low molecular weight heparin or warfarin), the anticoagulant dose should be stable for at least 4 weeks without dose adjustment; D: Cardiovascular System: According to Fridericia's standard, the QTc interval for males is ≤ 450 ms, and for females it is ≤ 470 ms; 10. A pregnancy test must be performed within 7 days before the first use of the study drug for premenopausal women who are likely to have children. The blood pregnancy test must be negative and must be non-lactation; All enrolled patients (male or female) should take adequate contraceptive measures throughout the treatment period and within 3 months after the end of treatment;
Exclusion criteria
1. Persons already known to be allergic to the active ingredients or excipients of the study drugs (WJ05129 tablets) ； 2. Patients previously treated with AURORA A kinase inhibitors (Alisertib, LY3295668, etc.) ； 3. Subjects who received a potent cytochrome CYP3A inhibitor or inducer within 14 days prior to initial administration and who needed to take these drugs throughout the study period; 4. Participate in other clinical studies within 4 weeks prior to initial administration, except during the follow-up period of observational (non-interventional) clinical studies or interventional studies; 5. Inability to swallow drugs orally, or having a condition that seriously affects gastrointestinal absorption as judged by the investigator; 6. Pregnant or lactating women; 7. Two or more malignancies within 5 years prior to first administration. Except for early stage malignant neoplasms (carcinoma in situ or stage I neoplasms) that have been eradicated, such as adequately treated carcinoma in situ of the cervix, basal cell or squamous cell carcinoma, etc.; 8. Underwent major surgery (as determined by the investigator) or was undergoing surgical recovery within 4 weeks prior to initial dosing. Anti-tumor chemotherapy (eluting for 6 weeks for the last chemotherapy with nitrosourea or mitomycin), radiotherapy, targeted therapy, hormone therapy, immunotherapy, or biotherapy within 4 weeks prior to initial administration. Receive anti-tumor or immunomodulatory TCM or Chinese adult medicine preparations within 2 weeks before the first administration; 9. Patients with symptoms of central nervous system metastasis (if asymptomatic and not currently receiving corticosteroid treatment, they are allowed to be enrolled) or primary tumor disease of the central nervous system; 10. Spinal cord compression that cannot be treated radically by surgery and/or radiotherapy, or for previously diagnosed spinal cord compression that is treated without clinical evidence of disease stability ≥1 week prior to randomization; 11. No remission of toxicity after previous antitumor therapy, i.e., no regression to the level specified in baseline, nCI-CTCAE5.0 level 0\ 1 (except hair loss), or inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 2 years | It is suitable for the curative effect development stage.Objective Response Rate by RECIST 1.1. |
| DLT | 2 years | It is suitable for dose escalation .DLT is defined as any of AE that SMC considers to have occurred during the DLT observation period and may be causally related to WJ05129 and meet DLTcriteria. |
| The incidence of adverse events (AE) and serious adverse events (SAE) were assessed | 2 years | It is suitable for dose escalation and dose extension.Incidence and severity of adverse events (AE) and serious adverse events (SAE) as assessed according to NCI-CTCAE 5.0, as well as abnormalities in physical examination, ECOG score, vital signs, electrocardiogram, ophthalmic tests and laboratory tests. |
| MTD | 2 years | Defined as the dose level at which the estimated toxicity probability is closest to the target toxicity probability during the DLT observation period |
| RP2D | 2 years | RP2D will be determined based on a combination of safety, tolerability, PK and/or pharmacodynamic studies . |
| Incidence of Treatment-Emergent Adverse Events | 2 years | Incidence and severity of adverse events (AE) and serious adverse events (SAE) as assessed according to NCI-CTCAE 5.0, as well as abnormalities in physical examination, ECOG score, vital signs, electrocardiogram, ophthalmic tests and laboratory tests. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vd/F | 2 years | It is suitable for dose escalation and dose extension.Apparent volume of distribution |
| λz | 2 years | It is suitable for dose escalation and dose extension.elimination rate constant |
| DOR | 2 years | Duration of response |
| Cmax | 2 years | Maximum Plasma Concentration |
| PFS | 2 years | Progression-free survival |
| OS | 2 years | Overall survival |
| DCR | 2 years | Disease Control Rate |
| Tmax | 2 years | It is suitable for dose escalation and dose extension.Time to Cmax |
| AUC0-t | 2 years | It is suitable for dose escalation and dose extension.Area under the concentration versus time curve from time 0 to the last measurable concentration |
| AUC0-inf | 2 years | It is suitable for dose escalation and dose extension.AUC from time 0 to infinity |
| t1/2 | 2 years | It is suitable for dose escalation and dose extension.Elimination half life time |
| CL/F | 2 years | It is suitable for dose escalation and dose extension.Clearance |
Countries
China
Outcome results
None listed