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

Phase 1

Not yet recruiting

• 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
• Interventions: Drug: DP303c; Drug: Paclitaxel or docetaxel or irinotecan; Drug: Simmitinib tablets; Drug: Irinotecan liposomes

• Registration Number: NCT06577376
• Lead Sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-08
• Study First Submitted: 2024-08-21
• Study Start: 2024-08-26
• Study First Submitted QC: 2024-08-27
• Last Update Submitted: 2024-08-27
• Study First Posted: 2024-08-29
• Last Update Posted: 2024-08-29
• Primary Completion: 2026-08-26
• Study Completion: 2027-08-26

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 252

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 1, D1-D21, Q4W	Simmitinib tablets	DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 1, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W	Simmitinib tablets	DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
DP303c injection, dose level 1, Q2W + simmitinib tablets, dose level 2, D1-D21, Q4W	Simmitinib tablets	DP303c injection, dose level 1, intravenous drip, Q2W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
DP303c injection, dose level 2, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W	DP303c	DP303c injection, dose level 2, intravenous drip, Q3W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
DP303c injection, dose level 2, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W	Simmitinib tablets	DP303c injection, dose level 2, intravenous drip, Q3W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
DP303c RP2D + irinotecan liposomes RP2D	DP303c	-
Single agent chemotherapy chosen by researchers	Paclitaxel or docetaxel or irinotecan	Single agent chemotherapy chosen by researchers: paclitaxel, docetaxel, or irinotecan
DP303c RP2D + irinotecan liposomes RP2D	Irinotecan liposomes	-
DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 1, D1-D21, Q4W	DP303c	DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 1, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W	DP303c	DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
DP303c injection, dose level 1, Q2W + simmitinib tablets, dose level 2, D1-D21, Q4W	DP303c	DP303c injection, dose level 1, intravenous drip, Q2W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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