An Open Label, Multicenter Phase I Clinical Study Evaluating the Safety, Tolerability, and Pharmacokinetic Characteristics of SIBP-A17 Formulation for Injection in Subjects With Advanced Solid Tumors.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 196
- 试验地点
- 1
- 主要终点
- Dose limiting toxicity (DLT)
研究概览
简要总结
To evaluate the safety, tolerability, and pharmacokinetic characteristics of SIBP-A17 and determine the maximum tolerable dose (MTD) and phase II recommended dose (RP2D).
详细描述
This study is an open, dose expanding, and indication expanding study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, preliminary anti-tumor efficacy, QT/QTc interval effects and explore potential biomarkers of SIBP-A17 in patients with advanced solid tumors.
This study is divided into two stages and is planned to be set up six dose groups, including 1, 2, 4, 5, 6, and 8 mg/kg. The first stage is the dose escalation stage, adopting an improved "3+3" dose escalation design, with a planned enrollment of 14-36 participants. The second stage is the dose expansion stage, where one or two doses are selected to enter the dose expansion phase (4 indication cohorts). 20-40 late-stage solid tumor participants are enrolled in each dose group for dose expansion, and 80-160 participants are planned to be enrolled in the dose expansion phase.
After obtaining certain safety and pharmacokinetic data during the dose escalation phase, the Safety Monitoring Committee (SMC) can discuss and decide whether to synchronize dose expansion.
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 of 18 to 75 years old (including boundary values), gender not limited.
- •The clinical diagnosis of enrolled subjects should meet the following criteria:
- •Dose escalation stage:
- •Advanced solid tumor subjects confirmed by histology or cytology to have no standard treatment plan or ineffective or intolerant standard treatment plan.
- •Dose expansion stage:
- •Cohort 1: Late/unresectable and/or metastatic breast cancer with low HER2 expression (IHC1+or IHC2+/FISH -) after standard treatment failure or intolerance.
- •Cohort 2: HER2 positive (IHC3+or IHC2+and FISH+) local advanced or metastatic digestive system tumors that fail or are not tolerated after standard treatment, including adenocarcinoma of stomach or gastroesophageal junction, colorectal cancer, etc. (pancreatic cancer and biliary tract cancer are excluded).
- •Cohort 3: HER2 positive (IHC3+or IHC2+with FISH+) advanced gynecological tumors that have failed or are intolerant to standard treatment, including but not limited to cervical cancer, endometrial cancer, and ovarian cancer.
- •Cohort 4: Other advanced solid tumors with HER2 expression that failed or were intolerant after standard treatment were preferentially included but not limited to HER2 positive (IHC3+or IHC2+and FISH+) breast cancer (at least 10 cases included), non-small cell lung cancer, etc.
- •Willing and able to provide sufficient fresh collected or archived tumor tissue samples (only applicable during dose expansion phase).
- •There must be at least one measurable lesion as the target lesion (according to RECIST v1.1 criteria, CT or MRI). Lesions that have received previous radiotherapy or other local treatments are not considered as target lesions unless there is clear progression of the lesion.
- •The Eastern Cooperative Oncology Group (ECOG) score for physical fitness is 0 or Expected survival period ≥ 3 months.
- •During the screening period, the main organ functions were basically normal [no blood transfusion, granulocyte colony-stimulating factor (G-CSF), or other medical support was received within 14 days before the use of the experimental drug]
- •During the screening period, women of childbearing age with negative blood pregnancy test results and reproductive age subjects (including male subjects) who have no pregnancy plans during the trial period and within 6 months after the last dose and voluntarily take effective contraceptive measures.
- •Voluntarily participate in this study and sign the informed consent form.
排除标准
- •Patients with tumors as specified in the protocol
- •Individuals with a history of previous treatment or surgery, or those who have received anti-tumor treatment as specified in the protocol during the planned trial period.
- •Individuals with a history of previous illnesses or abnormal conditions as specified in the laboratory examination protocol.
- •Screening for individuals with positive Treponema pallidum antibodies during the screening period. Individuals with active hepatitis B virus (HBV) or hepatitis C virus (HCV).
- •Patients with ascites, pleural effusion, and pericardial effusion accompanied by clinical symptoms during the screening period who require drainage, or those who have undergone serosal fluid drainage within 4 weeks before the first administration.
- •The screening period is accompanied by severe, progressive, or uncontrolled diseases, and it has been assessed by the researchers that participation in the study would increase the risk for the subjects.
- •History of interstitial lung disease/non infectious pneumonia in the past, currently suffering from interstitial lung disease/non infectious pneumonia, or suspected interstitial lung disease/non infectious pneumonia that cannot be excluded through imaging examination during screening.
- •Subjects who have experienced severe infections within 4 weeks prior to their first medication. Active infections that have received therapeutic intravenous antibiotics within 2 weeks prior to the first medication. Subjects receiving prophylactic antibiotic treatment can be enrolled.
- •Participants who have participated in any clinical trial as subjects within the first 3 months of enrollment (excluding subjects who have only participated in clinical trial screening and have not used the investigational drug).
- •According to the judgment of the investigator, there are concomitant diseases (such as severe diabetes, thyroid disease, etc.) that seriously endanger the safety of the subject or affect the completion of the study.
- •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.
- •Researchers believe that participants who are not suitable for enrollment.
研究组 & 干预措施
SIBP-A17
SIBP-A17 is an Her2-ADC drug.
干预措施: SIBP-A17 (Drug)
结局指标
主要结局
Dose limiting toxicity (DLT)
时间窗: Day 126
During the dose escalation phase, the first treatment cycle (21 days after the first dose) after the subject's administration was determined by the investigator to have occurred events related to the investigational drug as specified in the protocol.
Recommended Phase II Dose (RP2D)
时间窗: Day 518
Recommended Phase II Dose The optimal dose for phase II clinical trial research obtained based on clinical trial results of phase I and literature review.
Adverse Events (AE)
时间窗: 28 days
That is adverse events, any adverse events that occurred to the participant during the study period.
Maximum tolerated dose (MTD)
时间窗: Day 260
The maximum tolerated dose (MTD) refers to the highest dose at which DLT does not occur in \<1/3 of subjects or ≤ 1/6 of subjects during the DLT observation period.
次要结局
- DCR (Disease control rate)(5 months)
- AUC (Area Under The Plasma Concentration Versus Time Curve)(15 days)
- PFS(Progression-free survival)(5 months)
- Cmax (Peak Plasma Concentration)(15 days)
- ORR(Objective Response Rate)(5 months)
- Δ QTcF(15 days)
- OS (overall survival)(5 months)