Cadonilimab Combination With Chemotherapy With or Without AK117 in Resectable Gastric or Gastroesophageal Junction Adenocarcinoma

Study Overview
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Brief Summary
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This trial is a Phase II study. All patients are resectable Gastric or Gastroesophageal Junction Adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status 0-1.The purpose of this study is to evaluate the efficacy and safety of cadonilimab combined with chemotherapy with or without AK117 neoadjuvantin treatment of resectable Gastric or Gastroesophageal Junction Adenocarcinoma.

Official Title
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Phase II Clinical Study of Cadonilimab Combination With Chemotherapy With or Without the Anti-CD47 Antibody AK117 Neoadjuvant/Adjuvant Therapy for Resectable Gastric or Gastroesophageal Junction Adenocarcinoma

Conditions
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Resectable Gastric or Gastroesophageal Junction Adenocarcinoma

Intervention / Treatment
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* Drug: Cadonilimab
* Drug: AK117
* Drug: Oxaliplatin
* Drug: Tegafur-gimeracil-oteracil potassium
* Drug: Docetaxel
* Drug: 5-Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be able and willing to provide written informed consent. 18 to 75 years old. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Has a histologically confirmed diagnosis of Gastric or Gastroesophageal Junction Adenocarcinoma(G/GEJ). Has Stage T3-4N+M0 G/GEJ (American Joint Committee on Cancer [AJCC]) Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Has adequate organ function. Exclusion Criteria: Are there suspected metastases or locally advanced, unresectable disease, regardless of disease stage. Is currently participating in a study of an investigational agent or using an investigational device. Has undergone major surgery within 30 days of Study Day 1. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). History of myocardial infarction, unstable angina, congestive heart failure within 12 months prior to day 1 of study treatment. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study. Has received a live virus vaccine within 30 days of the planned first dose of study therapy.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 cohort 1<br>Subjects receive cadonilimab combination chemotherapy(SOX) neoadjuvant therapy 3 cycles. | Drug: Cadonilimab<br>* IV infusion,Specified dose on specified days<br>Drug: Oxaliplatin<br>* IV infusion,Specified dose on specified days<br>Drug: Tegafur-gimeracil-oteracil potassium<br>* Oral,Specified dose on specified days<br>|
| Experimental: Part 1 cohort 2<br>Subjects receive cadonilimab combination chemotherapy(SOX) and AK117 neoadjuvant therapy 3 cycles. | Drug: Cadonilimab<br>* IV infusion,Specified dose on specified days<br>Drug: AK117<br>* IV infusion,Specified dose on specified days<br>Drug: Oxaliplatin<br>* IV infusion,Specified dose on specified days<br>Drug: Tegafur-gimeracil-oteracil potassium<br>* Oral,Specified dose on specified days<br>|
| Experimental: Part 2 cohort 1<br>Subjects receive cadonilimab combination chemotherapy(FLOT) neoadjuvant therapy 4 cycles. | Drug: Cadonilimab<br>* IV infusion,Specified dose on specified days<br>Drug: Oxaliplatin<br>* IV infusion,Specified dose on specified days<br>Drug: Docetaxel<br>* IV infusion,Specified dose on specified days<br>Drug: 5-Fluorouracil<br>* IV infusion,Specified dose on specified days<br>|
| Experimental: Part 2 cohort 2<br>Subjects receive cadonilimab combination chemotherapy(FLOT) and AK117 neoadjuvant therapy 4 cycles. | Drug: Cadonilimab<br>* IV infusion,Specified dose on specified days<br>Drug: AK117<br>* IV infusion,Specified dose on specified days<br>Drug: Oxaliplatin<br>* IV infusion,Specified dose on specified days<br>Drug: Docetaxel<br>* IV infusion,Specified dose on specified days<br>Drug: 5-Fluorouracil<br>* IV infusion,Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AE), rate of surgical delays, abnormal laboratory findings of clinical significance |  | Up to approximately 2 years | 
| Pathological complete response (pCR) rates | pCR is defined the 0% residual viable tumor cells in the primary tumor and sampled lymph nodes | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathological response(MPR) rates | MPR is defined the ≤10% residual viable tumor cells in the primary tumor and sampled lymph nodes | Up to approximately 2 years | 
| Tumor regression grade(TRG) |  | Up to approximately 2 years | 
| R0 resection rate |  | Up to approximately 2 years | 
| Tumor descending stage rate | Proportion of subjects whose tumor TNM stage decreased from baseline before surgery | Up to approximately 2 years | 
| ORR |  | Up to approximately 2 years | 
| EFS |  | Up to approximately 2 years | 
| OS |  | Up to approximately 2 years | 
| PK | Serum drug concentrations of cadonilimab and/or AK117 in individual subjects at different time points | Up to approximately 2 years | 
| ADA | Number of subjects with detectable anti-drug antibodies (ADA). | Up to approximately 2 years |