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
Overview
- Phase
- Phase 1
- Intervention
- DP303c
- Conditions
- Localized Advanced or Metastatic Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma
- Sponsor
- Shanghai Runshi Pharmaceutical Technology Co., Ltd
- Enrollment
- 252
- Primary Endpoint
- Dose-limiting toxicity(DLT) occurrence and incidence
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
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
- •\*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;
Arms & Interventions
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
Intervention: DP303c
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
Intervention: Simmitinib tablets
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
Intervention: DP303c
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
Intervention: Simmitinib tablets
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
Intervention: DP303c
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
Intervention: Simmitinib tablets
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
Intervention: DP303c
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
Intervention: Simmitinib tablets
DP303c RP2D + irinotecan liposomes RP2D
Intervention: DP303c
DP303c RP2D + irinotecan liposomes RP2D
Intervention: Irinotecan liposomes
Single agent chemotherapy chosen by researchers
Single agent chemotherapy chosen by researchers: paclitaxel, docetaxel, or irinotecan
Intervention: Paclitaxel or docetaxel or irinotecan
Outcomes
Primary Outcomes
Dose-limiting toxicity(DLT) occurrence and incidence
Time Frame: Up to approximately 36 months after the first participant is enrolled
Adverse events (AE) occurrence and incidence
Time Frame: Up to approximately 36 months after the first participant is enrolled
Objective response rate (ORR) per RECIST 1.1
Time Frame: Up to approximately 36 months after the first participant is enrolled
Serious adverse events (SAE) occurrence and incidence
Time Frame: Up to approximately 36 months after the first participant is enrolled
Secondary Outcomes
- 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)