A Phase IB/II Clinical Study to Assess the Efficacy and Safety of QLS31905 in Combination With Chemotherapy as First-line Treatment in Patients With Claudin 18.2 (CLDN18.2) Positive Advanced Malignant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 115
- 试验地点
- 1
- 主要终点
- Phase 2 Recommended Dose（RP2D)(Part A)
研究概览
简要总结
This study aims to evaluate the efficacy and safety of QLS31905 plus chemotherapy in patients with Claudin18.2-positive advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Subjects voluntarily participate in the study and sign the informed consent form;
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
- •Expected survival time ≥ 3 months;
- •Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors;
- •No prior systemic anti-tumor treatment for locally advanced unresectable or metastatic disease;
- •Tumor tissue samples determined to have moderate-to-high Claudin18.2 expression by immunohistochemistry (IHC);
- •At least one measurable lesion per RECIST v1.1;
- •Patients with adequate cardiac, liver, renal function, etc.
排除标准
- •History of malignancies other than the target cancer within 5 years prior to the first dose of the investigational product ;
- •Underwent major organ surgery (excluding needle biopsy) or had significant trauma within 28 days prior to enrollment, or requires elective surgery during the study;
- •Known central nervous system metastases;
- •Patients with hepatitis B; patients with hepatitis C; patients who test positive for syphilis, or patients with a known history of HIV or positive HIV screening test;
- •Patients with a known history of psychoactive drug abuse, alcohol abuse, or substance abuse;
- •Patients with added risks associated with the study or may interfere with the interpretation of study results as determined by the investigator, or deemed unsuitable by the investigator and/or sponsor.
研究组 & 干预措施
QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)
Pancreatic cancer participants will be treated with QLS31905 in combination with nab-paclitaxel and gemcitabine for part A of the study to establish the recommended dose of QLS31905 for part B. In part B, the participants will be treated with QLS31905 at a dose determined by the part A of the study in combination with nab-paclitaxel and gemcitabine.
干预措施: QLS31905 (Drug)
QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)
Pancreatic cancer participants will be treated with QLS31905 in combination with nab-paclitaxel and gemcitabine for part A of the study to establish the recommended dose of QLS31905 for part B. In part B, the participants will be treated with QLS31905 at a dose determined by the part A of the study in combination with nab-paclitaxel and gemcitabine.
干预措施: Nab paclitaxel (Drug)
QLS31905 + nab-paclitaxel + gemcitabine (Part A/B)
Pancreatic cancer participants will be treated with QLS31905 in combination with nab-paclitaxel and gemcitabine for part A of the study to establish the recommended dose of QLS31905 for part B. In part B, the participants will be treated with QLS31905 at a dose determined by the part A of the study in combination with nab-paclitaxel and gemcitabine.
干预措施: Gemcitabine (Drug)
QLS31905 + oxaliplatin + capecitabine (Part B)
In part B, gastric/gastroesophageal junction cancer participants will be treated with QLS31905 at dose determined by part A of the study in combination with oxaliplatin and capecitabine.
干预措施: QLS31905 (Drug)
QLS31905 + oxaliplatin + capecitabine (Part B)
In part B, gastric/gastroesophageal junction cancer participants will be treated with QLS31905 at dose determined by part A of the study in combination with oxaliplatin and capecitabine.
干预措施: Oxaliplatin (Drug)
QLS31905 + oxaliplatin + capecitabine (Part B)
In part B, gastric/gastroesophageal junction cancer participants will be treated with QLS31905 at dose determined by part A of the study in combination with oxaliplatin and capecitabine.
干预措施: Capecitabine (Drug)
QLS31905 + gemcitabine+cisplatin(Part B)
In part B, other solid tumor participants including but not limited to biliary tract cancer will be treated with QLS31905 at dose determined by part A in combination with standard chemotherapy recommended by guidelines.QLS31905 plus gemcitabine+ cisplatin as the first-line treatment of advanced biliary tract cancer.
干预措施: QLS31905 (Drug)
QLS31905 + gemcitabine+cisplatin(Part B)
In part B, other solid tumor participants including but not limited to biliary tract cancer will be treated with QLS31905 at dose determined by part A in combination with standard chemotherapy recommended by guidelines.QLS31905 plus gemcitabine+ cisplatin as the first-line treatment of advanced biliary tract cancer.
干预措施: Gemcitabine (Drug)
QLS31905 + gemcitabine+cisplatin(Part B)
In part B, other solid tumor participants including but not limited to biliary tract cancer will be treated with QLS31905 at dose determined by part A in combination with standard chemotherapy recommended by guidelines.QLS31905 plus gemcitabine+ cisplatin as the first-line treatment of advanced biliary tract cancer.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Phase 2 Recommended Dose（RP2D)(Part A)
时间窗: Approximately 12 months
Monitor for MTD, and minimal efficacious dose by monitoring responses at different dose levels.
Maximum Tolerated Dose (MTD) (Part A)
时间窗: Approximately 12 months
As measured by number of participants experiencing dose related toxicity (DLT) in each escalating cohort.
Objective response rate (ORR)(Part B)
时间窗: Approximately 12 months
ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by investigator evaluation per RECIST 1.1.
次要结局
- Safety assessed by incidence of serious adverse events (SAE)(Approximately 12 months)
- PK of QLS31905: Time of the maximum concentration (Tmax)(Approximately 12 months)
- PK of QLS31905: Terminal elimination half-life (T1/2)(Approximately 12 months)
- Progression Free Survival(PFS)(Approximately 12 months)
- Safety assessed by Adverse Events (AEs)(Approximately 12 months)
- Overall Survival (OS)(Approximately 12 months)
- Number of participants with laboratory value abnormalities and/or adverse events (AEs)(Approximately 12 months)
- Duration Of Response (DOR)(Approximately 12 months)
- Pharmacokinetics(PK) of QLS31905: Maximum concentration (Cmax)(Approximately 12 months)
- Number of anti-drug antibody (ADA) Positive Participants(Approximately 12 months)
- PK of QLS31905: Clearance (CL)(Approximately 12 months)
- PK of QLS31905: Apparent volume of distribution during the terminal phase (Vz)(Approximately 12 months)