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

Study Overview
=================
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.

Official Title
-----------------
Surgical Conversion of Candonilimab (AK104) Combined With Paclitaxel, S-1 and Apatinib for Unresectable Advanced Gastric(G)/Gastroesophageal Junction(GEJ) Cancer

Conditions
-----------------
Gastric Cancer

Intervention / Treatment
-----------------
* Drug: AK104
* Drug: Apatinib
* Drug: Paclitaxel
* Drug: S-1


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent. Clinically diagnosed unresectable stage IV gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma by CT/MRI/Positron Emission Tomography (PET) -CT. Not received prior systemic therapy for stage IV G/GEJ adenocarcinoma At least one measurable tumor lesion per RECIST v1.1; Major organ functions are adequate; Expected survival is ≥ 3 months; Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1; Exclusion Criteria: Human Epidermal GrowthFactor Receptor 2 (HER2)-positive G/GEJ adenocarcinoma; 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; Central nervous system, lung, or bone metastases; Known history of active or autoimmune disease; Known history of other malignancies; Known history of severe cardiovascular and cerebrovascular diseases; Known history of gastrointestinal bleeding within the past 3 months or significant tendency to gastrointestinal bleeding; Active infection or fever of unknown origin; Known history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, and severe impairment of lung function; Known history of immunodeficiency, positive HIV antibody (HIVAb) test, or other acquired or congenital immunodeficiency disorder, or active hepatitis; Known history of mental disorder or psychoactive substance abuse; Hypersensitivity to the drugs of this regimen;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK104 plus apatinib, paclitaxel and S-1<br>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. | Drug: AK104<br>* Subjects will receive AK104 until disease progression or for up to 6 cycles.<br>Drug: Apatinib<br>* Subjects will receive apatinib until disease progression or for up to 6 cycles.<br>Drug: Paclitaxel<br>* Subjects will receive paclitaxel until disease progression or for up to 6 cycles.<br>Drug: S-1<br>* Subjects will receive S-1 until disease progression or for up to 6 cycles.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 surgical conversion rate |  | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |