NCT07172126尚未招募1 期
A Phase I/II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TQB3201 Tablets in Patients With Advanced Prostate Cancer
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 291
- 试验地点
- 3
- 主要终点
- Dose Limiting Toxicity (DLT)
研究概览
简要总结
TQB3201 is an orally administered targeted protein chimera (PROTAC) drug in which one end of the drug is attached to a ligand that binds to Androgen Receptor (AR) and the other end to a ligand of E3 ligase (CRBN) via a linker. The phase I phase of this trial aims to evaluate the safety, tolerability, and pharmacokinetic characteristics of TQB3201 tablets for the treatment of advanced prostate cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed adenocarcinoma of the prostate;
- •Age≥ 18 years old (calculated from the date of signing the informed consent form);
- •Eastern Cooperative Oncology Group Performance Status(ECOG )score 0-1 points;
- •Presence of metastatic disease confirmed by imaging;
- •Serum testosterone level ≤ 1.73 nmol/L (50 ng/dL) at screening;
- •Sufficient samples should be provided for gene mutation detection to determine androgen receptor gene status.
- •Patients who have progressed on the basis of at least 1 new endocrine drug;
- •The laboratory inspection meets the following standards:
- •Hemoglobin (HGB) ≥90g/L;
- •Absolute neutrophil value (NEUT) ≥1.5×109/L;
- •Platelet count (PLT) ≥75×109/L.
- •Total bilirubin (TBIL) ≤2 times the upper limit of normal (ULN); (3×ULN for patients with Gilbert syndrome ≤);
- •Alanine transferase (ALT) and aspartate transferase (AST) ≤2.5× ULN. If accompanied by liver metastasis, ALT and AST ≤ 5× ULN;
- •Serum creatinine (CR) ≤1.5× ULN or creatinine clearance estimated by the Cockcroft-Gault glomerular filtration formula ≥ 60 mL/min.
- •Urine routine: urine protein <; If the urine protein is ≥, the 24-hour urine protein quantitative ≤ 1.0 g should be confirmed.
- •Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) ≤1.5× ULN (no anticoagulant therapy);
- •Cardiac color ultrasound assessment: left ventricular ejection fraction (LVEF) ≥50%; > 12-lead ECG assessment: QT interval corrected by Fridericia's formula (QTcF) <450ms (males).
- •Men of childbearing potential and their partners of the opposite sex must agree to take effective contraceptive measures from the signing of the informed consent form until 6 months after the last dose of study drug;
- •Subjects voluntarily joined this study, signed the informed consent form, and had good compliance.
排除标准
- •Subjects with brain metastases with symptoms or symptom control time of less than 1 month;
- •Within 5 years before the first dose of medication or other malignant tumors at the same time.
- •Imaging ( Computed Tomography or Magnetic Resonance Imaging) shows that the tumor/metastasis has invaded important blood vessels, or the tumor/metastasis is very likely to invade important blood vessels during the follow-up study period, causing major bleeding;
- •Severe bone damage caused by bone metastasis; Pathological fractures and spinal cord compression of important parts that occurred within the past 6 months or are expected to occur in the near future as judged by the investigator;
- •Pleural effusion, pericardial effusion or ascites that cannot be controlled and still needs to be repeatedly drained (judged by the investigator);
- •Diseases affecting intravenous injection and intravenous blood collection, or having multiple factors affecting oral drugs (such as inability to swallow, chronic diarrhea and intestinal obstruction, etc.);
- •Adverse reactions of previous treatment have not recovered to Common Terminology Criteria (CTC) adverse event (AE) v5.0 grade ≤1, except for grade 2 alopecia, grade 2 peripheral neurotoxicity, grade 2 anemia, non-clinically significant and asymptomatic laboratory abnormalities, hypothyroidism stable on hormone replacement therapy, and other toxicities judged by the investigator to have no safety risk;
- •Have previously used or plan to use other similar drugs during the study;
- •Those who have received surgery, radiotherapy, radiotherapy, or local therapy (such as radiofrequency ablation, freezing, high-energy focused ultrasound, etc.) for prostate cancer after being diagnosed with metastatic prostate cancer;
- •Previous use of 5-ɑ reductase inhibitors within 4 weeks before the first dose; Systemic treatment with estrogens, progesterones, steroids (except for temporary use for anti-allergic use); First-generation AR antagonists; targeted therapy; biological therapy; immunotherapy; nuclide therapy; Botanicals known to have antitumor or PSA-lowering effects; Study treatments in other clinical trials.
- •Those who have undergone major surgical treatment, obvious traumatic injuries, or are allowed to undergo major surgery during the expected study treatment period within 4 weeks before the first dose, or have long-term unhealed wounds or fractures. (Major surgery is defined as: surgery of grade 3 or above in the 2022 edition of the National Surgical Grading Catalogue).
- •Subjects with any bleeding or bleeding event ≥Common Terminology Criteria for Adverse Events（CTCAE ）grade 3 within 4 weeks before the first dose.
- •Active viral hepatitis with poor control.
- •Active syphilis infection requiring treatment; Presence of active tuberculosis, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, radiation pneumonitis requiring treatment, or active pneumonitis with clinical symptoms; Active or uncontrolled serious infection (≥CTC AE grade 2 infection);
- •Those who have a history of psychotropic substance abuse and cannot abstain from it, or have mental disorders or have a history of drug use.
- •Those who are ready to undergo or have previously received allogeneic bone marrow transplantation or solid organ transplantation, or have received hematopoietic stem cell transplantation within 60 days before the first dose, or have obvious host transplant responses;
- •Decompensated cirrhosis (Child-Pugh liver function grade B or C) or history of hepatic encephalopathy.
- •Suffering from major cardiovascular and cerebrovascular diseases；
- •Renal failure requiring hemodialysis or peritoneal dialysis;
- •History of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases;
- •Subjects who require immunosuppressive agents, or systemic, or absorbable topical hormone therapy for immunosuppressive purposes and continue to use it within 7 days prior to the first dose (daily dose of glucocorticoids <except 10 mg prednisone or other equivalent efficacy hormones);
- •Known allergy to the excipient components of the study drug;
- •History of pituitary or adrenal dysfunction;
- •Diseases that are serious or not well controlled and judged by the investigator to be at greater risk of entering this study, such as type 1 or type 2 diabetes, hyperlipidemia, thyroid disease, etc. that cannot be controlled by drugs.
- •Estimated insufficient compliance to participate in this clinical study.
研究组 & 干预措施
TQB3201 tablets
Experimental
Each enrolled subject received 28 consecutive days of administration, once daily after meals. (25mg, 50mg, 100mg, 200mg, 400mg, 800mg, 1200mg)
干预措施: TQB3201 tablets (Drug)
结局指标
主要结局
Dose Limiting Toxicity (DLT)
时间窗: Up to 28days
DLTs are defined as toxicities that occur from the first dose to the end of the first treatment cycle by the severity criteria related to the trial drug (according to Common Terminology Criteria for Adverse Events v5.0 toxicity evaluation criteria) .
Maximum tolerated dose (MTD)
时间窗: Up to 28days
The MTD was defined as the highest dose in ≥ 6 evaluable subjects without any of the following: 1. In the DLT evaluation window, DLT occurred in 2 out of 3 subjects; 2. In the DLT evaluation window, 1 of the first 3 subjects had DLT, and 3 more subjects were added and 1 case had ≥ DLT.
Phase II Recommended Dose (RP2D)
时间窗: Up to 2 years
The RP2D will be determined based on the safety and tolerability information of the Phase I dose escalation phase and the efficacy and safety information of the Phase II phase.
Radiographic progression-free survival (rPFS)
时间窗: Up to 2 years
The time from randomization to the first occurrence of either radiologically confirmed disease progression or death from any cause, whichever comes first.
次要结局
- The area under the curve (AUC)(cycle1 day1pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose, cycle1 day7, 14 pre-dose, cycle1 day 28 pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose)
- Peak concentration (Cmax)(cycle1 day1pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose, cycle1 day7, 14 pre-dose, cycle1 day 28 pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose)
- Adverse events (AEs)(Up to 2 years)
- Terminal half-life (T1/2)(cycle1 day1pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose, cycle1 day7, 14 pre-dose, cycle1 day 28 pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose)
- Apparent Clearance (CL/F)(cycle1 day1pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose, cycle1 day7, 14 pre-dose, cycle1 day 28 pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose)
- Volume of Distribution at Steady State (Vss/F)(cycle1 day1pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose, cycle1 day7, 14 pre-dose, cycle1 day 28 pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose)
- Objective Response Rate (ORR)(Up to 2 years)
- Prostate-Specific Antigen Response Rate(Up to 2 years)
- To PSA progression time(Up to 2 years)
- Time to symptomatic bone-related events (SSEs)(Up to 2 years)
- Overall Survival (OS)(Up to 2 years)
研究者
研究点 (3)
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