A Study to Evaluate the Tolerance and Pharmacokinetics of TQB3303 Tablets

Study Overview
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Brief Summary
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TQB3303 tablet is a small molecule oral drug inhibiting cyclin-dependent kinases 4 and 6 (CDK4 / 6). Based on current research, overexpression of positive regulatory proteins in the cell cycle is one of the important reasons for resistance to endocrine therapy. CDK4 / 6 is the key regulators of the cell cycle inhibiting tumor cell proliferation.

Official Title
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A Phase I, Open-label, Dose Escalation and Expansion Study to Evaluate the Tolerance and Pharmacokinetics of TQB3303 Tablets

Conditions
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Advanced Malignant Solid Tumor

Intervention / Treatment
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* Drug: TQB3303


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.≥ 18 years old. 2. Histologically or cytologically confirmed advanced malignant solid tumors, without conventional treatment methods or fail or relapse after treatment. 3.Has at least one measurable lesion (based on RECIST 1.1) or bone metastases. 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2; Life expectancy ≥12 weeks. 5. Adequate organ system function. 6.Understood and signed an informed consent form. 7. Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ；No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization. Exclusion Criteria: 1. Has diagnosed and/or treated additional malignancy with the exception of cured basal cell carcinoma of the skin and cervical carcinoma in situ. 2. Has received cytotoxic chemotherapy in 4 weeks, or mitomycin C or nitrosourea in 6 weeks. 3. Has received any anti-tumor treatment such as hormone therapy, radioimmunotherapy, molecular targeted therapy, immunotherapy or other biological therapy within 4 weeks. 4. Has received other CDK4 / 6 inhibitors. 5. Has known spinal cord compression, cancerous meningitis, newly diagnosed central nervous system metastasis or brain metastases with stable symptoms less than 4 weeks; asymptomatic and stable imaging without corticosteroid treatment. 6.Has received stem cell or bone marrow transplant. 7.Has multiple factors affecting oral medication. 8.Has uncured wounds or fracture, except of pathological fracture with bone metastases patients. 9.Has uncontrolled cardiovascular disease. 10.Has received CYP3A4 inhibitors or inducers during the screening period and during the trial. 11.Has drug abuse history that unable to abstain from or mental disorders. 12.urinary protein ≥ ++, and the 24-hour urine protein quantification > 1.0 g. 13. Has active hepatitis B or C. 14. Has a history of autoimmune disease, immunodeficiency. 15. Hypersensitivity to TQB3303 or its excipient. 16. Has participated in other clinical trials within 4 weeks before participating in this trial. 17. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQB3303 Tablet<br>TQB3303 Tablet administered orally once. Then TQB3303 Tablet administered orally, once daily in 28-day cycle after 7 days of first administration. | Drug: TQB3303<br>* TQB3303 tablet is a small molecule oral drug inhibiting cyclin-dependent kinases 4 and 6 (CDK4 / 6).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Subjects appear the following toxic reaction relate to the drug after treatment within 28 days ：III °or above of non-hematological toxicity, IV° hematological toxicity , III ° neutropenia associated with fever, III ° thrombocytopenia with bleeding， III ° QTc interval extended | Baseline up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Cmax is the maximum plasma concentration of TQB3303 or metabolite(s). | Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120 hours post-dose on single dose; Hour 0 of day 7,day 14,day21 on multiple dose and hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120 hours post-dose on multiple dose of day 28. | 
| Tmax | To characterize the pharmacokinetics of TQB3303 by assessment of time to reach maximum plasma concentration. | Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120 hours post-dose on single dose; Hour 0 of day 7,day 14,day21 on multiple dose and hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120 hours post-dose on multiple dose of day 28. | 
| AUC0-t | To characterize the pharmacokinetics of TQB3303 by assessment of area under the plasma concentration time curve from zero to infinity. | Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120 hours post-dose on single dose; Hour 0 of day 7, day 14, day21 on multiple dose and hour 0, 0.5, 1, 2, 3, 4, 6, 8, 11, 24, 48, 72, 120 hours post-dose on multiple dose of day 28. | 
| Overall response rate (ORR) | Percentage of participants achieving complete response (CR) and partial response (PR). | up to 96 weeks | 
| Disease control rate（DCR） | Percentage of participants achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD). | up to 96 weeks | 
| Duration of response (DOR) | DOR defined as time from earliest date of disease response to earliest date of disease progression based on radiographic assessment. | up to 96 weeks | 
| Progression-free survival (PFS) | PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause. | up to 96 weeks |