A PhaseⅠ/Ⅱ Study of Simmitinib or Irinotecan Liposomes Combined With DP303c in Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma

Prior treatment

• Patients who have experienced toxicity during previous treatment with trastuzumab or trastuzumab biosimilars, resulting in permanent discontinuation of trastuzumab or trastuzumab biosimilars;
• There was a peripheral neuropathy of grade ≥ 2 (refer to NCI CTCAE 5.0) prior to enrollment;
• 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.

Other illness

• Patients with a history of allergies to any component of DP303c and deemed severe by the researchers
• Active leptomeningeal disease or uncontrolled CNS metastasis;
• Has a history of serious cardiovascular and cerebrovascular diseases;
• 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;
• There are eye diseases that require intervention, such as corneal diseases, retinal diseases, or active eye infections;

Other

• \*Eligibility Criteria:
• There is uncontrolled serosal fluid accumulation that requires frequent drainage or medical intervention;
• Urine protein ≥++ and 24-hour urine protein quantification\>1.0 g during screening period;

• 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
• 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