A Phase I Clinical Trial Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SIBP-A19 Injection in the Treatment of Advanced Malignant Solid Tumor Patients
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 156
- 试验地点
- 1
- 主要终点
- AE (Adverse Events)
研究概览
简要总结
To evaluate the safety, tolerability, and pharmacokinetic characteristics of SIBP-A19 and determine the maximum tolerable dose (MTD) and phase II recommended dose (RP2D).
详细描述
This study is an open label, multicenter, dose escalation, dose expansion, and indication expansion study to evaluate safety, tolerability, pharmacokinetics, preliminary anti-tumor efficacy, immunogenicity, impact on QT/QTc interval, and explore potential biomarkers of SIBP-A19 for injection in participants with advanced or metastatic solid tumors.
This study is divided into three stages and is planned to be set up eight dose groups, including 1.0, 2.0, 3.2, 4.0, 4.8, 5.6, 6.4 and 8.0 mg/kg. The first stage is the dose escalation stage, which will start from the first and second doses for enrollment. If necessary, a 3+3 dose escalation design will be used. The second stage is the dose expansion stage, where two or more doses are selected to enter the dose expansion phase, and 6-9 participants will be enrolled in each dose group for dose expansion. The third stage is the indication expansion stage, where phase II recommended dose (RP2D) is preliminarily determined based on the escalation and expansion of dosage in the early stage. Using RP2D for indication expansion, the investigators plan to expand three indication cohorts, with at least 30 participants selected for each cohort.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age range from 18 to 75 years old (including boundary values), regardless of gender.
- •Voluntarily participate in this study and sign the informed consent form.
- •Participants with advanced or metastatic solid tumors diagnosed by histology or cytology, without standard treatment, standard treatment failure, or intolerance.
- •Willing and able to provide sufficient fresh collected or archived tumor tissue samples or provide testing reports from legitimate institutions that meet the requirements.
- •There must be at least one measurable lesion as the target lesion.
- •ECOG score 0-
- •Expected survival time ≥ 3 months.
- •During the screening period, the main organ functions were basically normal (no medical support such as blood transfusion, granulocyte colony-stimulating factor (G-CSF), or other medical support was received within 14 days before the use of the investigational drug):
- •Blood routine: Absolute value of neutrophils (NE #) ≥ 1.5 × 10 9/L, platelet (PLT) count
- •≥ 90 × 10 9/L, hemoglobin (HGB) ≥ 90 g/L.
- •Women of childbearing age during the screening period who have a negative blood pregnancy test and are capable of reproduction (including male participants) have no pregnancy plan and voluntarily take effective contraceptive measures during the trial period and within 6 months after the last dose.
排除标准
- •Participants with the following tumors:
- •The participant has had other malignant tumors that have not been cured within the past 5 years (excluding malignant tumors that have been clearly cured, such as thyroid cancer, cured basal cell carcinoma of the skin, and cervical carcinoma in situ).
- •The participant has untreated imaging confirmed central nervous system metastasis.
- •Meningeal metastases.
- •Patients with brain metastases who have received systematic or curative brain metastasis treatment (radiotherapy or surgery) in the past, have been confirmed stable by imaging for at least 4 weeks, and have stopped systemic hormone, antiepileptic, convulsive drugs, and other treatments for more than 2 weeks without clinical symptoms can be enrolled.
- •Participants with a history of previous treatment or surgery, or those who received the following anti-tumor treatments during the planned trial period:
- •Patients who accepted the instructions clearly containing traditional Chinese patent medicines and simple preparations with anti-tumor effect within 2 weeks before the first administration;
- •Patients undergoing adjuvant therapy within 6 months after surgery;
- •Patients who have not recovered from the toxicity of the previous anti-tumor treatment to normal or ≤ level 1 (excluding hair loss);
- •Patients who have undergone major surgery, radiation therapy, biological therapy, or chemotherapy within 4 weeks prior to their first administration, or who have received systemic treatment such as unhealed surgical wounds, ulcers or fractures, or other clinical trial drugs.
- •Patients who plan to receive any other anti-tumor treatment (chemotherapy, radiation therapy, immunotherapy, cytokine therapy other than erythropoietin) during the trial period should be excluded (excluding testosterone lowering therapy for prostate cancer patients).
- •The dose (prednisone>10 mg/d or equivalent) at which immunosuppressive effects are achieved by receiving immunosuppressive agents or systemic corticosteroids within one week prior to the use of the investigational drug.
- •Participants with a history of previous illnesses or laboratory tests that show the following abnormalities:
- •Individuals with abnormal coagulation function and a tendency to bleed, or who are undergoing thrombolysis or anticoagulation treatment or have lost blood or donated more than 400 mL within 2 months prior to administration.
- •Have a history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation.
- •Have a clear history of neurological or psychiatric disorders, including epilepsy or dementia.
- •Known history of drug abuse, alcoholism, or drug use that may affect the results of the trial.
- •According to the investigator's judgment, the screening period is accompanied by serious, progressive, or uncontrolled diseases, and the investigator's assessment determines that the participant's participation in the study will increase the risk.
- •According to the investigator's judgment, there are serious accompanying diseases that pose a threat to patient safety or affect the completion of the study.
- •Patients with uncontrolled ascites, pleural effusion, pericardial effusion during the screening period or those who require drainage, or those who have undergone serosal fluid drainage within 4 weeks before the first administration.
- •Patients who must take supplements containing folic acid (such as those with folate deficiency).
- •Individuals with a history of severe allergies to protein products, CHO cell products, other recombinant human or humanized antibodies, or components of the investigational drug.
- •Pregnant and lactating women.
- •Patients who are deemed unsuitable to participate in this clinical study due to other reasons by the investigators.
研究组 & 干预措施
SIBP-A19
The participants enrolled will be sequentially assigned to the corresponding dose level.
干预措施: SIBP-A19 (Drug)
结局指标
主要结局
AE (Adverse Events)
时间窗: From day 1 after the first dose to day 28 after the last dose
That is adverse events, any adverse events that occurred to the participant during the study period.
Phase II recommended dose (RP2D)
时间窗: Day 21 after the last dose in the dose expansion phase
RP2D refers to the recommended dose determined through initial dose escalation and toxicity assessment in clinical trials, used for further evaluation of drug efficacy and safety.
Dose-limiting toxicity (DLT)
时间窗: Day 21 after each dose in the dose escalation stage
DLT is defined as any adverse event related to the drug defined in the protocol that occurs within 21 days of the first cycle after a single administration.
Maximum tolerated dose (MTD)
时间窗: Day 21 after the last dose in the dose escalation stage
MTD is defined as the maximum dose at which the number of DLT cases occurring during the DLT observation period within 21 days after a single administration is ≤ 1/6 of the total number of cases.
次要结局
- AUC (Area Under The Plasma Concentration Versus Time Curve)(Day 1, Day 22 and Day 63 after the first dose)
- Cmax (Peak Plasma Concentration)(Day 1, Day 22 and Day 63 after the first dose)
- Tmax (Peak Time)(Day 1, Day 22 and Day 63 after the first dose)
- ORR (Objective Response Rate)(6 weeks after the last evaluation)
- DCR (Disease control rate)(6 weeks after the last evaluation)
- PFS (Progression-free survival)(6 weeks after the last evaluation)
- OS (overall survival)(6 weeks after the last evaluation)