Surgical Conversion of Candonilimab (AK104) Plus Paclitaxel, S-1 and Apatinib for Unresectable Advanced G/GEJ Cancer

Phase 2

Recruiting

• Conditions: Gastric Cancer
• Interventions: Drug: AK104; Drug: Apatinib; Drug: Paclitaxel; Drug: S-1

• Registration Number: NCT05853172
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

Brief Summary

This is a prospective, single-arm, open-label，single-center, phase II study, aiming to to evaluate the surgical conversion feasibility of AK104 combined with apatinib, paclitaxel and S-1 in unresectable stage IV G/GEJ cancer.

Detailed Description

Eligible patients receive AK104 (10mg/kg, iv, Q3W) combined with apatinib (250mg, po, qd), paclitaxel (non-peritoneal metastasis: 130mg/m2, iv, D1; peritoneal metastasis :90mg/m2, iv, 40mg/m2, ip, D1) and S-1(60mg, po, bid, D1-D14) for up to 6 cycles. Patients assessed by Multi-Disciplinary Treatment (MDT) to meet the criteria for surgical resection undergo gastrectomy.

Study Timeline

• Study Start: 2023-03-21
• Status Verified: 2023-04
• Study First Submitted: 2023-04-24
• Study First Submitted QC: 2023-05-07
• Last Update Submitted: 2023-05-07
• Study First Posted: 2023-05-10
• Last Update Posted: 2023-05-10
• Primary Completion: 2025-03-21
• Study Completion: 2025-12-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
2. Clinically diagnosed unresectable stage IV gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma by CT/MRI/Positron Emission Tomography (PET) -CT.
3. Not received prior systemic therapy for stage IV G/GEJ adenocarcinoma
4. At least one measurable tumor lesion per RECIST v1.1;
5. Major organ functions are adequate;
6. Expected survival is ≥ 3 months;
7. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1;

Exclusion Criteria

1. Human Epidermal GrowthFactor Receptor 2 (HER2)-positive G/GEJ adenocarcinoma;
2. Previously received immune checkpoint inhibitors, including but not limited to programmed death 1 (PD-1) inhibitors and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors;
3. Central nervous system, lung, or bone metastases;
4. Known history of active or autoimmune disease;
5. Known history of other malignancies;
6. Known history of severe cardiovascular and cerebrovascular diseases;
7. Known history of gastrointestinal bleeding within the past 3 months or significant tendency to gastrointestinal bleeding;
8. Active infection or fever of unknown origin;
9. Known history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, and severe impairment of lung function;
10. Known history of immunodeficiency, positive HIV antibody (HIVAb) test, or other acquired or congenital immunodeficiency disorder, or active hepatitis;
11. Known history of mental disorder or psychoactive substance abuse;
12. Hypersensitivity to the drugs of this regimen;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AK104 plus apatinib, paclitaxel and S-1	Apatinib	AK104 (10mg/kg, iv, Q3W) is combined with apatinib (250mg, po, qd), paclitaxel (non-peritoneal metastasis: 130mg/m2, iv, D1; peritoneal metastasis: 90mg/m2, iv, 40mg/m2, ip, D1) and S-1(60mg, po, bid, D1-D14) for up to 6 cycle for up to 6 cycles.
AK104 plus apatinib, paclitaxel and S-1	Paclitaxel	AK104 (10mg/kg, iv, Q3W) is combined with apatinib (250mg, po, qd), paclitaxel (non-peritoneal metastasis: 130mg/m2, iv, D1; peritoneal metastasis: 90mg/m2, iv, 40mg/m2, ip, D1) and S-1(60mg, po, bid, D1-D14) for up to 6 cycle for up to 6 cycles.
AK104 plus apatinib, paclitaxel and S-1	S-1	AK104 (10mg/kg, iv, Q3W) is combined with apatinib (250mg, po, qd), paclitaxel (non-peritoneal metastasis: 130mg/m2, iv, D1; peritoneal metastasis: 90mg/m2, iv, 40mg/m2, ip, D1) and S-1(60mg, po, bid, D1-D14) for up to 6 cycle for up to 6 cycles.
AK104 plus apatinib, paclitaxel and S-1	AK104	AK104 (10mg/kg, iv, Q3W) is combined with apatinib (250mg, po, qd), paclitaxel (non-peritoneal metastasis: 130mg/m2, iv, D1; peritoneal metastasis: 90mg/m2, iv, 40mg/m2, ip, D1) and S-1(60mg, po, bid, D1-D14) for up to 6 cycle for up to 6 cycles.

Primary Outcome Measures

Name	Time	Method
R0 surgical conversion rate	up to 2 years

Secondary Outcome Measures

Name	Time	Method
R0 resection rate	up to 2 years
Pathological complete response (pCR)	up to 2 years
Pathological major response (MPR)	up to 2 years
Objective response rate (ORR)	up to 2 years
Disease control rate (DCR)	up to 2 years
Progression-free survival (PFS)	up to 2 years
Adverse event (AE)	up to 2 years

Trial Locations

Locations (1)

Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, China