A Phase 1/2a Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of JAB-21822 in Combination With JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 27
- 主要终点
- recommended phase-2 dose (RP2D).
研究概览
简要总结
This is a multicenter, open-label phase 1/2a study consisting of two parts: dose escalation phase and dose expansion phase. The objective of the dose escalation phase is to evaluate the safety, tolerability and pharmacokinetics of JAB-21822 in combination with JAB-3312 in patients with advanced solid tumors harboring KRAS p.G12C mutation and to determine the RP2D for the combination therapy. In the dose expansion phase, preliminary efficacy and safety of the combination therapy at the RP2D will be further explored in patients with specific cancer harboring KRAS p.G12C mutation.
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
- •A written informed consent should be signed by a subject or his/her legal representative before any study-related procedures are performed;
- •Subjects with histologically or cytologically confirmed locally advanced or metastatic advanced solid tumors harboring KRAS p.G12C mutation who have failed or lack standard-of-care (SOC) or are unwilling to undergo or intolerant to SOC;
- •Expected survival ≥ 3 months;
- •Subjects must have at least one measurable lesion as defined by RECIST v1.
- •If no measurable lesion untreated with radiation is selected as the target lesion, a lesion treated with radiation ≥ 4 weeks before the first dose and with progression confirmed by radiography may be selected as the target lesion;
- •Eastern Cooperative Oncology Group(ECOG) performance status 0-1;
- •The organ functions of subjects meet the criteria for the following laboratory parameters at screening;
- •Subjects must be able to swallow oral medications without gastrointestinal abnormalities that significantly affect drug absorption
排除标准
- •Patients with previous (≤ 3 years) or current tumors of other pathological types, except for cured cervical carcinoma in situ, ductal carcinoma in situ of the breast, prostatic intraepithelial neoplasia, superficial non-invasive bladder cancer, stage I skin cancer (except melanoma); subjects without recurrence or metastasis for > 3 years after treatment, without current evidence of tumor, and without significant risk of recurrence of previous malignant diseases in the opinion of the study doctor may also be enrolled;
- •Serious allergy to the investigational drug or excipients (such as microcrystalline cellulose, etc.);
- •Patients with previous (≤ 6 months before the initiation of treatment) or current severe autoimmune diseases (including adverse reactions caused by previous anti- tumor immunotherapies), or autoimmune diseases requiring long-term systemic hormone therapy at immunosuppressive dose levels (prednisone > 10 mg/day or equivalent drugs);
- •HIV, hepatitis B virus(HBV), or hepatitis C virus(HCV) positive;
- •Previous (≤ 6 months prior to the first dose) or current evidence of the following diseases: acute myocardial infarction, unstable angina and cerebrovascular accident;
- •Subjects who have impaired cardiac functions or clinically significant cardiac diseases;
- •Pregnant or lactating women
研究组 & 干预措施
Dose escalation
干预措施: JAB-21822 (Drug)
Dose escalation
干预措施: JAB-3312 (Drug)
Dose expansion
干预措施: JAB-3312 (Drug)
Dose expansion
干预措施: JAB-21822 (Drug)
结局指标
主要结局
recommended phase-2 dose (RP2D).
时间窗: Approximately 2 years
RP2D should be selected based on a comprehensive assessment of maximum tolerated dose(MTD), toxicity, pharmacokinetic(PK) profile, and efficacy data.
Number of participants with dose limiting toxicities
时间窗: Approximately 2 years
Dose-limiting toxicity (DLT) is defined as an adverse event (AE) or clinically significant abnormal laboratory value occurring in Cycle 1 (DLT assessment period), which is unrelated to progressive disease, concurrent disease, or concomitant medication but related to JAB-21822 and/or JAB-3312, and meets the criteria for DLT.
次要结局
- Number of participants with AEs(Approximately 2 years)
- Objective response rate (ORR)(Approximately 2 years)
- Progression-free survival (PFS)(Approximately 2 years)