Advanced Solid Tumors
Conditions
Brief summary
This is a study to evaluate the maximum tolerated dose (MTD) , occurrence of all adverse events (AE) and serious adverse events (SAE) , pharmacokinetic parameters and antitumor effect of TQB3558 tablets in Chinese adult patients with advanced solid tumors .The study is divided into phase Ia and phase Ib. Phase Ia: dose escalation period, to evaluate the safety and tolerability of TQB3558 tablets, determine MTD; Phase Ib: effectiveness exploration period, to expand the safe and effective dose group, recommend appropriate dosage and method for subsequent clinical research.
Interventions
DRUGTQB3558
TQB3558 is a kinase inhibitor of the TRK protein family.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Histologically or cytologically confirmed advanced malignant solid tumors, without conventional treatment methods or fail or relapse after treatment. 2\. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; Life expectancy ≥12 weeks. 3\. Has at least one measurable lesion (based on RECIST 1.1) or bone metastases. 4. Adequate organ system function. 5. Patients need to adopt effective methods of contraception. 6. Understood and signed an informed consent form.
Exclusion criteria
* 1\. Has received TRK inhibitors. 2. Has participated in any other clinical trials, or used other anti-cancer drugs, or received major surgical operations within 4 weeks before first administration. 3\. Has received local radiotherapy within 7 days or bone marrow radiotherapy within 4 weeks before the first administration. 4\. Has other malignant tumors in 2 years, except for cured or locally curable cancers. 5\. Has known spinal cord compression and cancerous meningitis. 6. Has interstitial lung disease, drug-induced interstitial lung disease, history of radiation lung disease requiring steroid therapy. 7\. Uncontrollable pleural effusion, pericardial effusion or ascites requiring repeated drainage. 8\. Obvious cardiovascular diseases. 9. Has a history of autoimmune disease, immunodeficiency. 10. Lactating women. 11. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) | Baseline up to 28 days | MTD was defined as the dose in which more than 2 of up to 6 patients developed a DLT. |
| Adverse events (AE) and serious adverse events (SAE) | Baseline up to 28 days | The occurrence of all adverse events (AE) and serious adverse events (SAE). |
| Overall response rate (ORR) | up to 96 weeks | Percentage of participants achieving complete response (CR) and partial response (PR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CL/f | 15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11. | CL/f is total clearance rate for TQB3558. |
| Disease control rate（DCR） | up to 96 weeks | Percentage of participants achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD). |
| AUC0-t | 15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11. | To characterize the pharmacokinetics of TQB3558 by assessment of area under the plasma concentration time curve from zero to infinity. |
| Duration of Response (DOR) | up to 96 weeks | DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment. |
| Progression-free survival (PFS) | up to 96 weeks | PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause. |
| Tmax | 15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11. | To characterize the pharmacokinetics of TQB3558 by assessment of time to reach maximum plasma concentration. |
| Cmax | 15minutes, 30minutes, 1hour, 2hour, 4hour, 6hour, 8hour,10hour, 24hour, 48hour post-dose on day 1 and day 11; 30minutes pre-dose on day 1, day 5, day 7,day 8 ,day 9 and day 11. | Cmax is the maximum plasma concentration of TQB3558 or metabolite(s). |
Countries
China
Contacts
Primary ContactZan Shen, Doctor
Outcome results
None listed