A Phase 1, Multi-Center, Open-Label Study to Assess Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of BAT6021 as Mono Therapy or in Combination With Tislelizumab in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 5
- 试验地点
- 3
- 主要终点
- Dose-limiting toxicity(DLT)
研究概览
简要总结
Main purpose:
- To evaluate the safety and tolerability of BAT6021 injection in the treatment of locally advanced or metastatic solid tumors with single drug or combined with tislelizumab(anti PD-1 monoclonal antibody);
- Explore the maximum tolerated dose (MTD) or maximum dosing dose (MAD) of BAT6021 injection monotherapy or in combination with tislelizumab and provide recommended dose and reasonable dosing regimen for phase II or subsequent clinical studies.
Secondary purpose:
- To evaluate the pharmacokinetic (PK) characteristics of BAT6021 injection with single or multiple doses of tislelizumab in patients with locally advanced or metastatic solid tumors;
- Evaluate the immunogenicity of BAT6021 injection;
- To evaluate the pharmacodynamics of BAT6021 injection;
- Preliminary evaluation of the anti-tumor efficacy of BAT6021 injection alone or in combination with tislelizumab.
详细描述
This study design for center, openness, dose escalation, and expand the research of phase I clinical trials, research the main evaluation BAT6021 injection for single or combined Tislelizumab in patients with advanced malignant solid tumors in the safety, tolerability and PK characteristics, to explore the maximum tolerated dose and preliminary antitumor efficacy, provide the basis for subsequent clinical trials recommended dose.
The study is divided into two parts:
Part I: single drug dose escalation study. Accelerated titration and "3+3" dose escalation rule were used to explore the safety, tolerability and pharmacokinetic characteristics of BAT6021.
Since the clinical benefit of a single agent may be limited, the study used accelerated titration and the "3+3" dose-escalation rule to explore the safe dose range from the ethical point of view of exposing fewer subjects to ineffective doses. A total of 8 dose groups were set up, including 1mg (initial dose) group, 3mg group, 10mg group, 30mg group, 100mg group, 300mg group, 600mg group and 900mg group, respectively. The whole is divided into two phases. The first stage: 1mg group, 3mg group, 10mg group using accelerated titration method dose increase. The second stage: 30mg group, 100mg group, 300mg group, 600mg group, 900mg group according to the standard "3+3" rule for dose increase study.
If MTD is found, the sponsor may select a dose of MTD or lower as the recommended dose for phase II clinical studies after discussion with the investigator based on the specific situation. If MTD is not reached, the sponsor may select a dose of MAD or one of the following dose groups as the recommended dose for phase II clinical studies, depending on the specific situation and discussion with the investigator. As the study progresses, protocols may be allowed to revise the definition of DLT as appropriate in light of new clinical findings. Adverse events that meet DLT criteria occurring outside the DLT evaluation period or other adverse safety information that the investigator considers meaningful do not directly influence dose-escalation decisions, but should be taken into account in the final determination of THE RP2D. Prior to each dose increase, the sponsor and investigator will discuss and comprehensively evaluate the decision to increase or decrease the dose, using available information on safety, PK (if any), and efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: ≥18 years old, gender: male or female;
- •The expected survival was assessed as at least 3 months;
- •ECOG physical status score is required to be 0 or 1;
- •Patients with locally advanced or metastatic malignant solid tumors confirmed by histology or cytology without standard therapy, failure of standard therapy, or inapplicable standard therapy;
- •According to RECIST 1.1, there must be evaluable tumor focus in dose increase stage, and at least one measurable tumor focus in dose expansion stage;
- •Fertile women must have a negative serum pregnancy test within 7 days prior to the first dose and be willing to use an effective method of birth control/contraception to prevent pregnancy during the study period up to 6 months after the last dose. Male patients must agree to use an effective contraceptive method for the duration of the study until 6 months after the study's last dosing; Postmenopausal women must be amenorrhea for at least 12 months before they are considered infertile.
排除标准
- •Prior treatment with anti-TiGit monoclonal antibody or anti-TiGit active double antibody;
- •Are receiving or are expected to receive other anti-tumor therapies during the study period, including but not limited to chemotherapy, radiotherapy, immunotherapy, hormone therapy (except alternative therapy), targeted therapy, biotherapy and proprietary Chinese medicines with anti-tumor effects;
- •3, first study drug delivery from previous antineoplastic therapy (chemotherapy and endocrine therapy, targeted therapy, immunotherapy, or tumor embolization, etc.) less than three weeks or five half-lives of longer (in time), the last time or distance large radiotherapy under 3 weeks (range palliative radiotherapy for bone metastases should full 2 weeks). Or less than 2 weeks since the last treatment with anti-tumor indications of proprietary Chinese medicine/immunomodulatory drugs (including thymosin, interferon, interleukin, etc.), or less than 8 weeks since the last radiation therapy;
- •Received other unmarketed investigational drugs or treatments within 4 weeks prior to the first use of the investigational drug;
- •Have received live/attenuated or mRNA vaccine within 4 weeks prior to screening or plan to receive live/attenuated or mRNA vaccine during the study period;
- •Pregnant or lactating women;
- •Patients whose AE caused by previous antitumor therapy did not recover to CTCAE 5.0≤ 1, except hair loss;
- •Patients with primary CNS tumor or symptomatic CNS metastasis should be excluded. Patients with meningeal metastasis or previous history of epilepsy should be excluded. Patients with clinically controlled CNS metastases who are asymptomatic or symptomatic but stable as determined by the investigator may be included, provided that the following conditions are met: Disease stability ≥4 weeks before first administration; B. Cranial MRI enhancement found no evidence of progression of central nervous system disease within 4 weeks prior to initial administration; C. Antiepileptic drugs have been discontinued and prednisone dosage ≤10mg/ day or equivalent hormone dosage ≥2 weeks before the first medication;
- •Patients who underwent major organ surgery (excluding needle biopsy) within 4 weeks prior to the first use of the study drug or have not recovered from the surgery, or have suffered significant trauma, or need to undergo elective surgery during the study period;
- •Those with a history of tissue or organ transplantation;
研究组 & 干预措施
G/"standard 3 + 3"
600mg of BAT6021
干预措施: BAT6021 (Drug)
E/"standard 3 + 3"
100mg of BAT6021
干预措施: BAT6021 (Drug)
F/"standard 3 + 3"
300mg of BAT6021
干预措施: BAT6021 (Drug)
A/ Accelerated titration
1mg of BAT6021
干预措施: BAT6021 (Drug)
B/ Accelerated titration
3mg of BAT6021
干预措施: BAT6021 (Drug)
C/ Accelerated titration
10mg of BAT6021
干预措施: BAT6021 (Drug)
D/"standard 3 + 3"
30mg of BAT6021
干预措施: BAT6021 (Drug)
H/"standard 3 + 3"
900mg of BAT6021
干预措施: BAT6021 (Drug)
结局指标
主要结局
Dose-limiting toxicity(DLT)
时间窗: 3 weeks
Dose-limiting toxicity (DLT) is defined as AE that occurred during the observation period of DLT and are considered to be at least possibly related to the drug under study, as follows: Grade 5 toxicity; Hematological toxicity: Grade 4 anemia; Grade 4 thrombocytopenia lasting ≥7 days; Grade 3 thrombocytopenia with bleeding(grade ≥2) or requiring platelet transfusion; Grade 4 neutropenia ≥7 days or grade 3 neutropenia with infection ≥7 days; Grade ≥3 neutropenia with fever; Non-hematological toxicity: Grade ≥3 non-hematological toxicity (AE not detected by simple laboratory tests); Grade 3 or 4 non-hematological toxicity detected by clinical laboratory tests that meets any of the following criteria: (1) Clinical intervention is required; (2) Resulting in hospitalization; (3) Any treatment-related toxicities resulting in a delay of more than 2 weeks in cycle 2 administration;
maximum tolerated dose (MTD)
时间窗: 3 weeks
MTD was defined as the highest dose level of DLT observed in ≤1/6 subjects in a dose group during the DLT evaluation period
次要结局
- Pharmacokinetics (PK)(every cycle until cycle 6 (one cycle equals 3 weeks))
- Immunogenicity(every cycle until cycle 6 (one cycle equals 3 weeks))