A Phase IB/II Clinical Study on the Safety, Tolerability and Efficacy of HRS-4642 in Combination With Anti-tumor Medication in Subjects With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Phase IB: Safety endpoints: adverse events (AEs).
研究概览
简要总结
The study is being conducted to evaluate the safety, tolerability, and efficacy of HRS-4642 in combination with antitumor medicine in patients with advanced solid tumors harboring KRAS G12D mutation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
- •Male or female ≥ 18 years old and ≤75 years old.
- •ECOG performance status of 0-
- •With a life expectancy of ≥12 weeks.
- •With unresectable locally advanced or metastatic solid tumors harbouring with KRAS G12D mutation confirmed by central laboratory testing.
- •Need to provided tumor tissue samples for genetic testing.
- •Have at least one measurable lesion according to RECIST1.1, and the dose-escalation phase allows no measurable lesion.
- •Adequate laboratory parameters during the screening period.
排除标准
- •Accompanied by untreated or active central nervous system (CNS) metastases. Subjects with a history or current history of meningeal metastasis.
- •Systemic antitumor therapy was received 4 weeks before the start of the study.
- •Palliative radiotherapy was completed within 14 days before the first dose.
- •Toxicity and/or complications from previous interventions did not return to NCI-CTCAE level ≤1 or exclusion criteria.
- •Subjects with known or suspected interstitial pneumonia.
- •Moderate or severe ascites with clinical symptoms; Uncontrolled or moderate or higher pleural effusion or pericardial effusion.
- •Have poorly controlled or severe cardiovascular disease.
- •Subjects with active hepatitis B or active hepatitis C.
- •A history of immunodeficiency, including a positive HIV test, other acquired or congenital immunodeficiency disorders, or a history of organ transplantation.
- •The presence of uncontrolled mental illness and other conditions known to affect the completion of the study process, such as alcohol, drug or substance abuse, and criminal detention.
- •Any other factors that may increase the risk of participating in the study, interfere with the study results, or make participation in the study inappropriate as judged by investigators.
研究组 & 干预措施
Arm 1
For HRS-4642 in combination with Adebrelimab or in combination with Adebrelimab and chemotherapy for advanced solid tumors with KRAS G12D mutations.
干预措施: HRS-4642 (Drug)
Arm 1
For HRS-4642 in combination with Adebrelimab or in combination with Adebrelimab and chemotherapy for advanced solid tumors with KRAS G12D mutations.
干预措施: Adebrelimab (Drug)
Arm 1
For HRS-4642 in combination with Adebrelimab or in combination with Adebrelimab and chemotherapy for advanced solid tumors with KRAS G12D mutations.
干预措施: Pemetrexed Disodium for Injection、Cisplatin Injection、Carboplatin for Injection (Drug)
Arm 2
For HRS-4642 in combination with SHR-9839，for advanced solid tumors with KRAS G12D mutations.
干预措施: HRS-4642 (Drug)
Arm 2
For HRS-4642 in combination with SHR-9839，for advanced solid tumors with KRAS G12D mutations.
干预措施: SHR-9839 (Drug)
Arm 3
For HRS-4642 in combination with Cetuximab Solution for Infusion，for advanced solid tumors with KRAS G12D mutations
干预措施: HRS-4642 (Drug)
Arm 3
For HRS-4642 in combination with Cetuximab Solution for Infusion，for advanced solid tumors with KRAS G12D mutations
干预措施: Cetuximab Solution for Infusion (Drug)
结局指标
主要结局
Phase IB: Safety endpoints: adverse events (AEs).
时间窗: 24 months
Assess safety and tolerability by way of adverse events (CTCAE v5.0).
Phase IB： Maximum tolerated dose (MTD)
时间窗: From Day 1 to Day 21
Incidence and category of dose limiting toxicities (DLTs) during the first 21-day cycle of treatment.
Phase IB：Recommended phase 2 dose (RP2D)
时间窗: 24 months
RP2D will be determined on the basis of evaluation on safety, PK, efficacy data in dose escalation and dose expansion stages.
Phase II: Overall response rate (ORR).
时间窗: 24 months.
Evaluated by RECIST v1.1.
次要结局
- Efficacy endpoints: Overall response rate (ORR).(24 months)
- Efficacy endpoints: Duration of response (DoR).(24 months)
- Efficacy endpoints: Disease control rate (DCR).(24 months)
- Efficacy endpoints: Progression free survival (PFS).(24 months)
- Efficacy endpoints: overall survival (OS).(24 months)