To Evaluate the Efficacy and Safety of Cadonilimab With SOX as Neoadjuvant Therapy for Resectable Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma.

Gastric Cancer Clinical Trial

Official title:

The Efficacy and Safety of Chemotherapy Combined With Cadonilimab (AK104) in Neoadjuvant Treatment of Locally Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma: A Prospective, Single-arm, Phase II Clinical Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05948449
• Other study ID #: WCH-2023-526
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2023
• Est. completion date: July 2025

Study information

• Verified date: July 2023
• Source: Sichuan University
• Contact: Jiankun Hu, M.D
• Phone: +86-18980601504
• Email: hujiankun[@]wchscu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The Purpose of This Study is to Evaluate the Efficacy and Safety of Cadonilimab（AK104） in Combination With SOX as Neoadjuvant Therapy for Patients With Resectable Locally Advanced Gastric or Gastroesophageal Adenocarcinoma.

Description:

Recent years, neoadjuvant therapy have emerged as a promising treatment option for the treatment of locally advanced gastric or gastroesophageal adenocarcinoma. However, the efficacy of current neoadjuvant regimens is still unsatisfactory. Novel treatment with higher efficacy and safety are urgently needed. Recently, immunotherapy has achieved significant therapeutic effects in the treatment of a series of cancers, and chemotherapy combined with immunotherapy has been recommended as the standard first-line treatment for gastric cancer. Moreover, several phase I/II studies have explored the efficacy and safety of chemotherapy combined with PD-1 inhibitor in the neoadjuvant treatment for gastric cancer, the results of which indicate that chemotherapy combined with immunotherapy can significantly improve the pCR rate and R0 resection rate of gastric cancer. In this study, we will evaluate the efficacy and safety of chemotherapy combined with Cadonilimab（AK104） (a PD-1/CTLA-4 bispecific antibody) in the neoadjuvant therapy for resectable locally advanced gastric or gastroesophageal adenocarcinoma.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 37
• Est. completion date: July 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age 18-75 years.

2. Histologically or cytologically confirmed diagnosis of adenocarcinoma locate at gastroesophageal junction or stomach, advanced gastric or gastroesophageal junction cancer as assessed by ultrasonography and/or CT/MRI (cT3-T4a, N+, M0).

3. Resectable gastric or gastroesophageal cancer, judged by surgeons in this study.

4. No previous anti-tumor treatment.

5. The expected survival is no less than 3 months.

6. ECOG PS=1.

7. Adequate organ function including the following:

• Total bilirubin =1.5 times upper limit of normal (ULN),
• Aspartate transaminase (AST) and alanine transaminase (ALT) =3×ULN,
• Alkaline phosphatase=2.5×ULN (If the tumor invaded the liver, =3×ULN),
• Serum creatinine=1.5×ULN,
• Serum amylase and lipase=1.5×ULN,
• International standardized ratio (INR)/partial prothrombin time (PTT)=1.5×ULN;
• Platelet count = 75,000 /mm3.
• Hemoglobin (Hb) = 9 g/dL.
• Absolute neutrophil count (ANC) = 1500/mm3.

8. Strict contraception.

9. Patients must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.

Exclusion Criteria:

1. Unable to comply with the research program or procedures.

2. Undergoing other drug clinical trials, or has participated in any drug clinical trials one month before enrollment.

3. Active autoimmune disease or history of refractory autoimmune disease.

4. Receiving corticosteroid (> 10mg/d prednisone or equivalent dose of steroids) or other systematic immunosuppression therapies within 14 days before enrollment, excluding following therapies: steroid hormone replacement therapy (=10mg/d); local steroid therapy; short-term, prophylactic steroid therapy for preventing allergies or nausea and vomiting.

5. Active or clinically significant cardiac disease:

• Congestive heart failure > New York Heart Association (NYHA ) class 2;
• Active coronary artery disease;
• Arrhythmias requiring treatment other than ß-blocker or digoxin;
• Unstable angina (with angina symptoms at rest), new angina within 3 months before enrollment, or new myocardial infarction within 6 months before enrollment

6. Evidence or history of bleeding diathesis or coagulopathy.

7. Grade 3 bleeding events 4 weeks before enrollment.

8. Thromboembolism or arteriovenous events, such as cerebrovascular events (including transient ischemic attack), deep vein thrombosis or pulmonary embolism, occurred 6 months before enrollment.

9. Currently taking anticoagulants.

10. Other tumors that have not been treated or exist at the same time, except carcinoma in situ of the cervix, treated basal cell carcinoma or superficial bladder tumor. If the tumor has been cured and no evidence of disease has been found for more than 3 years, the patient can be enrolled. All other tumors must be treated at least 3 years before enrollment.

11. Patients with pheochromocytoma.

12. Patients with a history of HIV infection or active hepatitis B/C.

13. Ongoing > level 2 infection.

14. Symptomatic brain metastasis or meningioma.

15. Unhealed wounds, ulcers or fractures.

16. Renal failure patients requiring blood or peritoneal dialysis.

17. Dehydration= 1 grade.

18. Epileptic that need medication.

19. Active, symptomatic interstitial pneumonia, pleural or ascites that causes dyspnea (dyspnea = 2 grade).

20. History of organ transplantation. (including corneal transplantation).

21. Allergic to research drugs or similar drugs, or suspected allergies.

22. Malabsorption patients.

23. Pregnant or lactating women.

24. Investigator believes that patients who are not suitable for the study.

25. Medical, psychological or social conditions can affect the recruitment of patients and evaluation for study results.

26. Other anti-tumor therapy (chemotherapy, radiotherapy, surgery, immunotherapy, biotherapy, chemoembolization) other than investigator drugs. Palliative external irradiation for non-target lesions is allowed.

27. Previously used oxaliplatin, S-1 or Cadonilimab.

28. Major surgery 4 weeks before recruitment, open biopsy or major trauma surgery. (excluding biliary stents, or percutaneous biliary drainage).

29. Treatment with anti-tumor Chinese herbal medicine.

30. History of allogeneic blood transfusion within 6 months.

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• S-1, Oxaliplatin, Cadonilimab
3 cycles of neoadjuvant therapy will be administered: S-1: 40~60mg Bid,d1~14, q3w Oxaliplatin:130mg/m2,iv drip,d1, q3w Cadonilimab(AK104):10mg/Kg,iv drip,d1,q3w

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sichuan University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response rate (pCR)	evaluate pathological complete response rate of primary tumor and locally metastatic lymph nodes after 3 cycles of neoadjuvant therapy.	From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
Secondary	R0 resection rate	Rate of microscopically margin-negative resection	From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
Secondary	2-year overall survival rate		2 years
Secondary	2-year disease free survival rate		2 year
Secondary	major pathological response (MPR)		From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
Secondary	Safety and Tolerability	Treatment-related adverse events as assessed by CTCAE v4.0	3 months after the last administration of drugs