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

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

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.

Study Overview

• Status: 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
• Intervention / Treatment: Drug: DP303c; Drug: Simmitinib tablets; Drug: Irinotecan liposomes; Drug: Paclitaxel or docetaxel or irinotecan

• Study Type: Interventional
• Enrollment (Estimated): 252
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 1, D1-D21, Q4W; DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 1, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W	Drug: DP303c; DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker; Drug: Simmitinib 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)
Experimental: DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W; DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W	Drug: DP303c; DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker; Drug: Simmitinib 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)
Experimental: DP303c injection, dose level 1, Q2W + simmitinib tablets, dose level 2, D1-D21, Q4W; DP303c injection, dose level 1, intravenous drip, Q2W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W	Drug: DP303c; DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker; Drug: Simmitinib 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)
Experimental: DP303c injection, dose level 2, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W; DP303c injection, dose level 2, intravenous drip, Q3W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W	Drug: DP303c; DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker; Drug: Simmitinib 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)
Experimental: DP303c RP2D + irinotecan liposomes RP2D	Drug: DP303c; DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker; Drug: Irinotecan liposomes; A chemotherapy
Active Comparator: Single agent chemotherapy chosen by researchers; Single agent chemotherapy chosen by researchers: paclitaxel, docetaxel, or irinotecan	Drug: Paclitaxel or docetaxel or irinotecan; Paclitaxel or docetaxel or irinotecan is used as a control.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): August 26, 2024
• Primary Completion (Estimated): August 26, 2026
• Study Completion (Estimated): August 26, 2027

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: August 27, 2024
• First Posted (Actual): August 29, 2024

Study Record Updates

• Last Update Posted (Estimated): September 5, 2024
• Last Update Submitted That Met QC Criteria: September 2, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Disease Progression; Adenocarcinoma; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Docetaxel; Paclitaxel; Irinotecan
• Other Study ID Numbers: SYSA1501-010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No