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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: AK104; Drug: Apatinib; Drug: Paclitaxel; Drug: S-1

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Han Liang, MD; Phone Number: 18622221082; Email: tjlianghan@126.com

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Tianjin Medical University Cancer Institute and Hospital
    • Contact: Han Liang, MD; Phone Number: 18622221082; Email: tjlianghan@126.com
    • Principal Investigator: Han Liang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Investigators: Principal Investigator: Han Liang, MD, Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2023
• Primary Completion (Anticipated): March 21, 2025
• Study Completion (Anticipated): December 21, 2025

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: May 7, 2023
• First Posted (Actual): May 10, 2023

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Paclitaxel; Apatinib
• Other Study ID Numbers: E20221047

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No