a phaseⅰ/ⅱ study of simmitinib or irinotecan liposomes combined with dp303c in gastric adenocarcinoma or gastroesophageal junction adenocarcinoma

Conditions: 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

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.


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 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 exclusion criteria: 1. patients who have experienced toxicity during previous treatment with trastuzumab or trastuzumab biosimilars, resulting in permanent discontinuation of trastuzumab or trastuzumab biosimilars; 2. patients with a history of allergies to any component of dp303c and deemed severe by the researchers 3. there is uncontrolled serosal fluid accumulation that requires frequent drainage or medical intervention; 4. active leptomeningeal disease or uncontrolled cns metastasis; 5. has a history of serious cardiovascular and cerebrovascular diseases; 6. there was a peripheral neuropathy of grade ≥ 2 (refer to nci ctcae 5.0) prior to enrollment; 7. history of gastrointestinal perforation and/or fistula within 6 months of first use of medication; 8. inability to swallow medication orally or presence of clinically significant gastrointestinal diseases; 9. urine protein ≥++ and 24-hour urine protein quantification\>1.0 g during screening period; 10. there are eye diseases that require intervention, such as corneal diseases, retinal diseases, or active eye infections; 11. used cyp3a4 strong inhibitors or cyp3a4 strong inducers 14 days before the first medication ; 12. used ugt1a1 strong inhibitor before first medication and wash-off period is less than 5 half-lives.