A Multicenter, Open-label Phase I/II Clinical Study to Evaluate the Safety and Efficacy of Simmitinib or Irinotecan Liposomes Combined With DP303c Injection in the Treatment of HER2 Expressing Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 252
- 主要终点
- Dose-limiting toxicity(DLT) occurrence and incidence
研究概览
简要总结
This study is divided into two parts: Cohort 1 and Cohort 2. Cohort 1 includes the dose escalation phase of DP303c combined with simmitinib, as well as the randomized controlled trial (RCT) phase of DP303c combined with simmitinib; Cohort 2 includes dose escalation/dose extension of DP303c combined with irinotecan liposomes, as well as RCT stage of DP303c combined with irinotecan liposomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18-75 (including) years old;
- •Gastric adenocarcinoma or gastroesophageal junction adenocarcinoma diagnosed by histology or cytology;
- •Disease progression after receiving one or two lines of systemic treatment in the past (first-line treatment must be platinum/fluorouracil combination chemotherapy with or without immune checkpoint inhibitors);
- •There should be at least one measurable lesion according to the response evaluation criteria in solid tumors (RECIST v1.1),;
- •HER2 expression status: 2+ to 3+(applicable to Cohort 1) or 1+(applicable to Cohort 2);
- •Adequate organ or bone marrow function
排除标准
- •*Eligibility Criteria:
- •Inclusion Criteria:
- •Aged 18-75 (including) years old;
- •Gastric adenocarcinoma or gastroesophageal junction adenocarcinoma diagnosed by histology or cytology;
- •Disease progression after receiving one or two lines of systemic treatment in the past (first-line treatment must be platinum/fluorouracil combination chemotherapy with or without immune checkpoint inhibitors);
- •There should be at least one measurable lesion according to the response evaluation criteria in solid tumors (RECIST v1.1),;
- •HER2 expression status: 2+ to 3+(applicable to Cohort 1) or 1+(applicable to Cohort 2);
- •Adequate organ or bone marrow function
- •Exclusion Criteria:
- •Patients who have experienced toxicity during previous treatment with trastuzumab or trastuzumab biosimilars, resulting in permanent discontinuation of trastuzumab or trastuzumab biosimilars;
- •Patients with a history of allergies to any component of DP303c and deemed severe by the researchers
- •There is uncontrolled serosal fluid accumulation that requires frequent drainage or medical intervention;
- •Active leptomeningeal disease or uncontrolled CNS metastasis;
- •Has a history of serious cardiovascular and cerebrovascular diseases;
- •There was a peripheral neuropathy of grade ≥ 2 (refer to NCI CTCAE 5.0) prior to enrollment;
- •History of gastrointestinal perforation and/or fistula within 6 months of first use of medication;
- •Inability to swallow medication orally or presence of clinically significant gastrointestinal diseases;
- •Urine protein ≥++ and 24-hour urine protein quantification>1.0 g during screening period;
- •There are eye diseases that require intervention, such as corneal diseases, retinal diseases, or active eye infections;
- •Used CYP3A4 strong inhibitors or CYP3A4 strong inducers 14 days before the first medication ;
- •Used UGT1A1 strong inhibitor before first medication and wash-off period is less than 5 half-lives.
研究组 & 干预措施
DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 1, D1-D21, Q4W
DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 1, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
干预措施: DP303c (Drug)
DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 1, D1-D21, Q4W
DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 1, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
干预措施: Simmitinib tablets (Drug)
DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W
DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
干预措施: DP303c (Drug)
DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W
DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
干预措施: Simmitinib tablets (Drug)
DP303c injection, dose level 1, Q2W + simmitinib tablets, dose level 2, D1-D21, Q4W
DP303c injection, dose level 1, intravenous drip, Q2W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
干预措施: DP303c (Drug)
DP303c injection, dose level 1, Q2W + simmitinib tablets, dose level 2, D1-D21, Q4W
DP303c injection, dose level 1, intravenous drip, Q2W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
干预措施: Simmitinib tablets (Drug)
DP303c injection, dose level 2, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W
DP303c injection, dose level 2, intravenous drip, Q3W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
干预措施: DP303c (Drug)
DP303c injection, dose level 2, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W
DP303c injection, dose level 2, intravenous drip, Q3W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
干预措施: Simmitinib tablets (Drug)
DP303c RP2D + irinotecan liposomes RP2D
干预措施: DP303c (Drug)
DP303c RP2D + irinotecan liposomes RP2D
干预措施: Irinotecan liposomes (Drug)
Single agent chemotherapy chosen by researchers
Single agent chemotherapy chosen by researchers: paclitaxel, docetaxel, or irinotecan
干预措施: Paclitaxel or docetaxel or irinotecan (Drug)
结局指标
主要结局
Dose-limiting toxicity(DLT) occurrence and incidence
时间窗: Up to approximately 36 months after the first participant is enrolled
Adverse events (AE) occurrence and incidence
时间窗: Up to approximately 36 months after the first participant is enrolled
Objective response rate (ORR) per RECIST 1.1
时间窗: Up to approximately 36 months after the first participant is enrolled
Serious adverse events (SAE) occurrence and incidence
时间窗: Up to approximately 36 months after the first participant is enrolled
次要结局
- Disease control rate (DCR) per RECIST 1.1(Up to approximately 36 months after the first participant is enrolled)
- Duration of response (DoR) per RECIST 1.1(Up to approximately 36 months after the first participant is enrolled)
- Overall survival(OS)(Up to approximately 36 months after the first participant is enrolled)
- Progression free survival (PFS) per RECIST 1.1(Up to approximately 36 months after the first participant is enrolled)
- Blood concentration of total anti-DP303c antibody(Up to approximately 36 months after the first participant is enrolled)
- Positive incidence of anti-DP303c antibody (ADA)(Up to approximately 36 months after the first participant is enrolled)
- HER2 expression level(Up to approximately 36 months after the first participant is enrolled)
- Blood concentration of simmitinib(Up to approximately 36 months after the first participant is enrolled)
- Blood drug concentration of DP303c(Up to approximately 36 months after the first participant is enrolled)