Clinical trial NCT06577376: A PhaseⅠ/Ⅱ Study of Simmitinib or Irinotecan Liposomes Combined With DP303c in Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd
Sponsor class: INDUSTRY
First posted: 2024-08-29
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Dose-limiting toxicity(DLT) occurrence and incidence
timeFrame: Up to approximately 36 months after the first participant is enrolled
measure: Adverse events (AE) occurrence and incidence
timeFrame: Up to approximately 36 months after the first participant is enrolled
measure: Objective response rate (ORR) per RECIST 1.1
timeFrame: Up to approximately 36 months after the first participant is enrolled
measure: Serious adverse events (SAE) occurrence and incidence
timeFrame: Up to approximately 36 months after the first participant is enrolled
Secondary outcomes:
measure: Disease control rate (DCR) per RECIST 1.1
timeFrame: Up to approximately 36 months after the first participant is enrolled
measure: Duration of response (DoR) per RECIST 1.1
timeFrame: Up to approximately 36 months after the first participant is enrolled
measure: Progression free survival (PFS) per RECIST 1.1
timeFrame: Up to approximately 36 months after the first participant is enrolled
measure: Overall survival(OS)
timeFrame: Up to approximately 36 months after the first participant is enrolled
measure: Blood drug concentration of DP303c
timeFrame: Up to approximately 36 months after the first participant is enrolled
measure: Blood concentration of total anti-DP303c antibody
timeFrame: Up to approximately 36 months after the first participant is enrolled
measure: Positive incidence of anti-DP303c antibody (ADA)
timeFrame: Up to approximately 36 months after the first participant is enrolled
measure: HER2 expression level
timeFrame: Up to approximately 36 months after the first participant is enrolled
measure: Blood concentration of simmitinib
timeFrame: Up to approximately 36 months after the first participant is enrolled
Other outcomes:
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Study officials:
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