Localized Advanced or Metastatic Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma, Expressing Human Epidermal Growth Factor Receptor-2 (HER-2), Disease Progression After Receiving at Least One and at Most Two Lines of Systemic Treatment in the Past
Conditions
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.
Interventions
DRUGDP303c
DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker
DRUGSimmitinib tablets
A novel small molecule inhibitor targeting fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR2, KDR), and colony-stimulating factor 1 receptor (CSF-1R)
A chemotherapy
DRUGPaclitaxel or docetaxel or irinotecan
Paclitaxel or docetaxel or irinotecan is used as a control.
Sponsors
Shanghai Runshi Pharmaceutical Technology Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
In the dose escalation phase, a 3+3 approach is used to explore the safety and tolerability of subjects, and in the randomized controlled phase, the efficacy of different combination doses is explored
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Aged 18-75 (including) years old; 2. Gastric adenocarcinoma or gastroesophageal junction adenocarcinoma diagnosed by histology or cytology; 3. 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); 4. There should be at least one measurable lesion according to the response evaluation criteria in solid tumors (RECIST v1.1),; 5. HER2 expression status: 2+ to 3+(applicable to Cohort 1) or 1+(applicable to Cohort 2); 6. Adequate organ or bone marrow function
Exclusion criteria
* \*Eligibility Criteria: Inclusion Criteria: 1. Aged 18-75 (including) years old; 2. Gastric adenocarcinoma or gastroesophageal junction adenocarcinoma diagnosed by histology or cytology; 3. 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); 4. There should be at least one measurable lesion according to the response evaluation criteria in solid tumors (RECIST v1.1),; 5. HER2 expression status: 2+ to 3+(applicable to Cohort 1) or 1+(applicable to Cohort 2); 6. Adequate organ or bone marrow function
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity(DLT) occurrence and incidence | Up to approximately 36 months after the first participant is enrolled |
| Adverse events (AE) occurrence and incidence | Up to approximately 36 months after the first participant is enrolled |
| Objective response rate (ORR) per RECIST 1.1 | Up to approximately 36 months after the first participant is enrolled |
| Serious adverse events (SAE) occurrence and incidence | Up to approximately 36 months after the first participant is enrolled |
Secondary
| Measure | Time frame |
|---|---|
| Blood drug concentration of DP303c | 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 |
| Disease control rate (DCR) per RECIST 1.1 | 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 |
| Positive incidence of anti-DP303c antibody (ADA) | 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 |
| Progression free survival (PFS) 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 |
Outcome results
None listed