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

Shanghai Runshi Pharmaceutical Technology

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Localized Advanced or Metastatic Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma; Disease Progression After Receiving at Least One and at Most Two Lines of Systemic Treatment in the Past; Expressing Human Epidermal Growth Factor Receptor-2 (HER-2)

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06577376

SYSA1501-010

Details and patient eligibility

About

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.

Enrollment: 252 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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252 participants in 6 patient groups

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

Experimental group

Description:

DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 1, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W

Treatment:

Drug: DP303c

Drug: Simmitinib tablets

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

Experimental group

Description:

DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W

Treatment:

Drug: DP303c

Drug: Simmitinib tablets

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

Experimental group

Description:

DP303c injection, dose level 1, intravenous drip, Q2W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W

Treatment:

Drug: DP303c

Drug: Simmitinib tablets

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

Experimental group

Description:

DP303c injection, dose level 2, intravenous drip, Q3W + simmitinib tablets, dose level 2, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W

Treatment:

Drug: DP303c

Drug: Simmitinib tablets

DP303c RP2D + irinotecan liposomes RP2D

Experimental group

Treatment:

Drug: Irinotecan liposomes

Drug: DP303c

Single agent chemotherapy chosen by researchers

Active Comparator group

Description:

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

Treatment:

Drug: Paclitaxel or docetaxel or irinotecan