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

NCT06577376 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: SYSA1501-010
• Study Type: interventional
• Target: 252
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (9)

• 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

Study Arms (6)

DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 1, D1-D21, Q4W

EXPERIMENTAL

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; Drug: Simmitinib tablets

DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W

EXPERIMENTAL

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; Drug: Simmitinib tablets

DP303c injection, dose level 1, Q2W + simmitinib tablets, dose level 2, D1-D21, Q4W

EXPERIMENTAL

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; Drug: Simmitinib tablets

DP303c injection, dose level 2, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W

EXPERIMENTAL

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; Drug: Simmitinib tablets

DP303c RP2D + irinotecan liposomes RP2D

EXPERIMENTAL

Drug: DP303c; Drug: Irinotecan liposomes

Single agent chemotherapy chosen by researchers

ACTIVE COMPARATOR

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

Drug: Paclitaxel or docetaxel or irinotecan

Interventions

DP303c DRUG

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

DP303c RP2D + irinotecan liposomes RP2D; DP303c injection, dose level 1, Q2W + simmitinib tablets, dose level 2, D1-D21, Q4W; DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 1, D1-D21, Q4W; DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W; DP303c injection, dose level 2, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W

Simmitinib tablets 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, Q3W + simmitinib tablets, dose level 1, D1-D21, Q4W; DP303c injection, dose level 1, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W; DP303c injection, dose level 2, Q3W + simmitinib tablets, dose level 2, D1-D21, Q4W

Irinotecan liposomes DRUG

A chemotherapy

DP303c RP2D + irinotecan liposomes RP2D

Paclitaxel or docetaxel or irinotecan DRUG

Paclitaxel or docetaxel or irinotecan is used as a control.

Single agent chemotherapy chosen by researchers

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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

You may not qualify if:

• \*Eligibility Criteria:
• Aged 18-75 (including) years old;
• Gastric adenocarcinoma or gastroesophageal junction adenocarcinoma diagnosed by histology or cytology;
• 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);
• There should be at least one measurable lesion according to the response evaluation criteria in solid tumors (RECIST v1.1),;
• HER2 expression status: 2+ to 3+(applicable to Cohort 1) or 1+(applicable to Cohort 2);
• Adequate organ or bone marrow function
• Patients who have experienced toxicity during previous treatment with trastuzumab or trastuzumab biosimilars, resulting in permanent discontinuation of trastuzumab or trastuzumab biosimilars;
• Patients with a history of allergies to any component of DP303c and deemed severe by the researchers
• There is uncontrolled serosal fluid accumulation that requires frequent drainage or medical intervention;
• Active leptomeningeal disease or uncontrolled CNS metastasis;
• Has a history of serious cardiovascular and cerebrovascular diseases;
• There was a peripheral neuropathy of grade ≥ 2 (refer to NCI CTCAE 5.0) prior to enrollment;
• History of gastrointestinal perforation and/or fistula within 6 months of first use of medication;
• Inability to swallow medication orally or presence of clinically significant gastrointestinal diseases;

Sponsors & Collaborators

• Shanghai Runshi Pharmaceutical Technology Co., Ltd: lead

MeSH Terms

Interventions

Paclitaxel; Docetaxel; Irinotecan

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: August 21, 2024
• First Posted: August 29, 2024
• Study Start: August 26, 2024
• Primary Completion (Estimated): August 26, 2026
• Study Completion (Estimated): August 26, 2027
• Last Updated: September 5, 2024

Record last verified: 2024-08