A Study of QL1604 Plus Nab-paclitaxel Versus Paclitaxel for Participants With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma That Progressed After Therapy With Platinum and Fluoropyrimidine
试验速览
- 阶段
- 2 期
- 入组人数
- 492
- 试验地点
- 1
- 主要终点
- The incidence and severity of adverse events (AE) and serious adverse events (SAE) according to CTCAE V5.0
研究概览
简要总结
This is a study for participants with advanced gastric or gastroesophageal junction adenocarcinoma who had tumor progression after first-line treatment with platinum and fluoropyrimidine doublet therapy. The study will be conducted in 2 parts.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Volunteer to participate in this clinical study; Completely understand and know this study as well as sign the informed consent form (ICF);
- •Age ≥ 18 years and ≤ 80 years when ICF is signed;
- •Have histologically or cytologically confirmed diagnosis of locally advanced, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma(G/GEJC).
- •Eastern Cooperative Oncology Group performance status of 0 or 1;
- •Life expectancy of at least 12 weeks;
- •Have measurable disease as defined by RECIST 1.1 as determined by the investigator;
- •Be willing to provide newly-obtained or paraffin-embedded tissue for PD-L1 and other biomarker analysis;
- •HER-2/neu negative；
- •Female subjects of childbearing potential should have a negative serum human chorionic gonadotropin(HCG) test within 7 days prior to receiving the first dose of study medication and are not breastfeeding;
- •Male and female subjects able to have children must agree to use highly effective method of contraception throughout the study and for at least 180 days after last dose.
排除标准
- •Has non-G/GEJC such as squamous cell carcinoma, adenosquamous carcinoma, undifferentiated gastric cancer;
- •Known allergy or hypersensitivity to QL1604/nab-paclitaxel/paclitaxel or any components used in the preparation;
- •Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease disease-relieving drugs, corticosteroids or immunosuppressant）;
- •Has a diagnosis of immunodeficiency or received systemic steroid therapy （>10mg daily of prednisone or equivalent drug）or any other form of immunosuppressive therapy within 14 days prior to the planned start of study therapy；
- •Subjects who have received radiotherapy, chemotherapy, monoclonal antibodies,targeted therapy, other anti-tumor treatments,or participating in other clinical studies is less than 4 weeks before the first dose of trial treatment;
- •Has a known additional malignancy that is progressing or requires active treatment in past 3 years;
- •Subjects with known central nervous system (CNS) metastasis;
- •Has a history of pneumonitis that required steroids in past 3 years;
- •Has an active infection requiring systemic therapy；
- •Subjects with the history of Human Immunodeficiency Virus (HIV)、acquired, congenital immunodeficiency diseases、organ transplant;
- •Has hepatitis B surface antigen (HBsAg) positive and/or hepatitis B core antibody (HBcAb) positive and HBV deoxyribonucleic acid (HBV DNA) >1000 copies/mL, or hepatitis C virus antibody positive;
- •Has received a live vaccine within 30 days of the planned start of study therapy；
- •Has received prior immune checkpoint inhibitors;
- •Known psychiatric or substance abuse disorders that would interfere with the requirements of the study;
- •Subjects with uncontrollable cardiac diseases;
- •Has accompanying diseases that seriously endanger the subject's safety or affect the study by the investigator;
- •Has any condition that increases the risk, interferes with the study results by the investigator, or investigators/sponsor consider the subjects are not suitable for this trial;
研究组 & 干预措施
Experimental: Cohort A
Participants receive QL1604 and nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle. If not disease progression after 4 cycles, participants receive QL1604 monotherapy until disease progression、unacceptable toxicity or up to 2 years.
干预措施: QL1604 (Drug)
Experimental: Cohort A
Participants receive QL1604 and nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle. If not disease progression after 4 cycles, participants receive QL1604 monotherapy until disease progression、unacceptable toxicity or up to 2 years.
干预措施: Nab-paclitaxel (Drug)
Experimental: Cohort B-arm1
Participants receive QL1604 and nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle. If not disease progression after 4 cycles, participants receive QL1604 monotherapy until disease progression、unacceptable toxicity or up to 2 years.
干预措施: QL1604 (Drug)
Experimental: Cohort B-arm1
Participants receive QL1604 and nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle. If not disease progression after 4 cycles, participants receive QL1604 monotherapy until disease progression、unacceptable toxicity or up to 2 years.
干预措施: Nab-paclitaxel (Drug)
Experimental: Cohort B-arm2
Participants receive paclitaxel on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
The incidence and severity of adverse events (AE) and serious adverse events (SAE) according to CTCAE V5.0
时间窗: Up to 90 days from last dose
Safety and tolerability (stage 1)
The percentages of participants discontinuing or suspending the study drug due to an AE.
时间窗: Up to 90 days from last dose
Safety and tolerability (stage 1)
Overall survival（OS）（stage 2）
时间窗: from the date of first dose until the date of death from any cause,assessed up to 2 years
Overall survival is defined as time from randomization to death due to any cause.
次要结局
- Disease control rate（DCR）assessed by the investigators according to RECIST 1.1（stage 1 and 2）(up to 2 years)
- Overall survival(stage 1)(from the date of first dose until the date of death from any cause,assessed up to 2 years)
- Peak plasma concentration (Cmax) following single dose administration of PD-1（stage 1 ）(through study completion, an average of 2 years)
- Steady-state trough serum concentration of multiple Dose Administration of PD-1（stage 2）(through study completion, an average of 2 years)
- Objective response rate（ORR）assessed by the investigators according to RECIST 1.1（stage 1 and 2）(up to 2 years)
- Tumor response rate（TRR）assessed by the investigators according to RECIST 1.1（stage 1 and 2）(up to 2 years)
- Progression-free survival（PFS）assessed by the investigators according to RECIST 1.1（stage 1 and 2）(up to 2 years)
- Area under the concentration-time curve (AUC ) following single dose administration of PD-1（stage 1 ）(through study completion, an average of 2 years)
- Steady-state peak serum concentration of multiple Dose Administration of PD-1（stage 2）(through study completion, an average of 2 years)
- Immunogenicity（stage 1 and 2）(through study completion, an average of 2 years)