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

NCT ID: NCT06577376

Last Updated: 2024-09-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 252 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-26
• Study Completion Date: 2027-08-26

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

DP303c

Intervention Type: DRUG

DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker

Simmitinib tablets

Intervention Type: DRUG

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)

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

Group Type: EXPERIMENTAL

DP303c

Intervention Type: DRUG

DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker

Simmitinib tablets

Intervention Type: DRUG

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)

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

Group Type: EXPERIMENTAL

DP303c

Intervention Type: DRUG

DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker

Simmitinib tablets

Intervention Type: DRUG

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)

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

Group Type: EXPERIMENTAL

DP303c

Intervention Type: DRUG

DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker

Simmitinib tablets

Intervention Type: DRUG

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)

DP303c RP2D + irinotecan liposomes RP2D

Group Type: EXPERIMENTAL

DP303c

Intervention Type: DRUG

DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker

Irinotecan liposomes

Intervention Type: DRUG

A chemotherapy

Single agent chemotherapy chosen by researchers

Single agent chemotherapy chosen by researchers: paclitaxel, docetaxel, or irinotecan

Group Type: ACTIVE_COMPARATOR

Paclitaxel or docetaxel or irinotecan

Intervention Type: DRUG

Paclitaxel or docetaxel or irinotecan is used as a control.

Interventions

DP303c

DP303c is an antibody conjugate drug (ADC), composed of one anti-HER2 monoclonal antibody coupled to one MMAE via an enzyme specific linker

Intervention Type: 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)

Intervention Type: DRUG

Irinotecan liposomes

A chemotherapy

Intervention Type: DRUG

Paclitaxel or docetaxel or irinotecan

Paclitaxel or docetaxel or irinotecan is used as a control.

Intervention Type: DRUG

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

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:

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Runshi Pharmaceutical Technology Co., Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

SYSA1501-010

Identifier Type: -

Identifier Source: org_study_id