The Efficacy and Safety of QL1706 As Second-line Treatment in Advanced Hepatocellular Carcinoma Patients Refractory to First-line Therapy: a Single-arm, Phase I Study
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Median progression-free survival(mPFS)
研究概览
简要总结
This is a phase I trial to assess the safety and preliminary efficacy of QL1706 in Treating Advanced Hepatocellular Carcinoma Patients refractory to prior immunotherapy.
详细描述
Immune checkpoint inhibitors (ICIs) have produced encouraging results in patients with hepatocellular carcinoma (HCC). Nonetheless, single-agent ICIs are effective in only 15% to 20% of HCC patients. According to the phase 3 LEAP-002 trial, lenvatinib combined with pembrolizumab provides a limited survival advantage over lenvatinib. In China, local treatments combined with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies have been used as the first-line treatment of advanced HCC. However, due to the heterogeneity of cancer, patient responses to monotherapy or combination therapy vary considerably, and only some patients benefit from such therapy. Hence, there is an unmet need to investigate the appropriate treatment for the rapidly expanding group of patients with advanced HCC who had tumor progression on prior anti-PD-1 therapies. QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t1/2) for CTLA-4. The Single-arm, single-center study aims to evaluate the safety and efficacy of QL1706 in treating advanced HCC refractory to prior PD-1 immune checkpoint inhibitors.
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
- •Subjects participate voluntarily and sign informed consent.
- •18 years ≤ age ≤ 75 years;
- •Child-Pugh liver function score ≤ 7;
- •ECOG PS 0-1;
- •No serious organic diseases of heart, lung, brain, kidney and other organs;
- •Enhanced MRI examination confirmed advanced hepatocellular carcinoma (CNLC stage II and above, Barcelona stage B and above);
- •Puncture biopsy confirming the pathologic type as hepatocellular carcinoma;
- •Disease progression after receiving first-line therapy(Progressed on/relapsed after at least one prior anti-PD-1 treatment).
排除标准
- •Pregnant and lactating women;
- •Suffering from diseases that affect the absorption, distribution, metabolism or clearance of the study drug (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorders, etc.);
- •A history of gastrointestinal bleeding within the previous 4 weeks or a definite predisposition to gastrointestinal bleeding (e.g., known locally active ulcer lesions, fecal occult blood of ++ or more, or gastroscopy if persistent fecal occult blood of +) that has not been treated in a targeted manner, or any other condition that may have caused gastrointestinal bleeding (e.g., severe fundal/esophageal varices) as determined by the investigator;
- •Active infections, including: HIV (HIV1/2 antibody) positive; active hepatitis B (HBsAg positive and abnormal liver function); active hepatitis C (HCV antibody positive or HCV RNA ≥103 copies/ml and abnormal liver function); active tuberculosis; and other uncontrolled active infections (CTCAE V5.0 >2 level);
- •Other significant clinical and laboratory abnormalities that, in the opinion of the investigator, affect the safety evaluation, e.g., uncontrolled diabetes mellitus, immunodeficiency disorders, chronic kidney disease, grade II or higher peripheral neuropathy (CTCAE V5.0), and abnormal thyroid function;
- •Prior use of anti-CTLA-4 antibody drugs.
- •Inability to follow the study protocol to receive treatment or follow up as scheduled.
研究组 & 干预措施
Experimental: QL1706
Drug: QL1706
干预措施: QL1706 (Drug)
结局指标
主要结局
Median progression-free survival(mPFS)
时间窗: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs earlier, assessed up to 1 year
measured from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.
次要结局
- overall response rate (ORR) measured by mRECIST criteria(rom the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 2 year)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](Up to 21 days post-the last treatment)
- Overall survival (OS)(from the date of first treatment to the date of death from any cause, assessed up to 2 year)
- Disease control rate (DCR)(from the date of first treatment to radiographically documented response according to mRECIST, assessed up to 2 year)
研究者
Wan-Guang Zhang
Professor
Tongji Hospital