CLDN18.2 Positive, Gastroesophageal Junction Adenocarcinoma, Primary Gastric Adenocarcinoma
Conditions
Brief summary
This study is a prospective, randomized, open, multicenter phase II clinical trial. It plans to enroll 70 participants with locally advanced gastric and gastroesophageal junction adenocarcinoma (G/GEJ AC) who are assessed as suitable for D2 radical surgery and capable of R0 resection.To evaluate the clinical efficacy and tolerability of IBI343 in combination with sintilimab and SOX regimen for perioperative treatment of resectable, locally advanced gastric or gastroesophageal junction adenocarcinoma.Enroll patients who are CLDN18.2 positive.
Interventions
DRUGIBI343,sintilimab,oxaliplatin,S-1
IBI343,sintilimab,oxaliplatin,S-1
DRUGsintilimab,oxaliplatin,S-1
sintilimab,oxaliplatin,S-1
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed written informed consent and able to comply with the visit and related procedures as specified in the protocol. 2. Male or female, 18 years ≤ age ≤ 75 years; 3. ECOG score 0-1; 4. Histologically confirmed, previously untreated patients with gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction; only Siewert II/III type participants are allowed for gastroesophageal junction cancer; 5. Clinical staging based on enhanced CT/MRI examination, clinical stage T3\~4a with positive lymph nodes, and no distant metastasis; 6. The research center and surgeon can perform radical D2 lymph node dissection surgery, R0 resection; 7. Physical condition and organ function allow for major abdominal surgery; 8. Confirmed CLDN18.2 expression by central laboratory pathological tissue testing. 9. Adequate organ and bone marrow function. 10. Echocardiography confirms left ventricular ejection fraction (LVEF) ≥ 50%; 11. Female participants must agree not to breastfeed from screening through the entire treatment period and up to 6 months after the last dose. 12. Female participants of childbearing potential or male participants whose partners are of childbearing potential must use effective contraception from screening through the entire treatment period and up to 9 months after the last dose.
Exclusion criteria
1. HER2 positive. 2. Currently participating in another interventional clinical study, except for those in the follow-up phase of an interventional study. 3. Previous use of traditional Chinese medicine, Chinese patent medicines, or immunomodulators must be ≥2 weeks before starting the study medication. 4. Received treatment with a strong CYP3A4 inhibitor within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose of the study drug. 5. Received any live vaccine within 4 weeks prior to the first dose of the study drug or plans to receive any during the study period. 6. Underwent major surgery (craniotomy, thoracotomy, laparotomy, laparoscopic resection of significant tissues or organs, or other as defined by the investigator, excluding needle biopsies) within 4 weeks prior to the first dose of the study drug, or has unhealed wounds, ulcers, or fractures. 7. Patients who received steroids (\>10 mg/day prednisone equivalent) or other immunosuppressive drugs within 14 days before enrollment. However, patients are allowed to enroll if they use topical or inhaled steroids, or adrenal replacement therapy with ≤10 mg/day prednisone equivalent, without active autoimmune disease. 8. History of interstitial lung disease, non-infectious pneumonia, severely impaired pulmonary function, or uncontrolled pulmonary disease such as pulmonary fibrosis, severe radiation pneumonitis, acute lung injury, etc., or suspected of having such conditions during the screening period. 9. Presence of uncontrolled diseases, such as: • Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg). 10. Any arterial thromboembolic event within 6 months prior to the first dose of the study drug, including myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, etc. 11. History of deep vein thrombosis (patients stable on anticoagulation for at least 2 weeks can be enrolled), pulmonary embolism, or any other serious venous thromboembolic event within 3 months prior to the first dose of the study drug (implantable venous port or catheter-related thrombosis, or superficial venous thrombosis, are not considered "serious" venous thromboembolic events). 12. Any life-threatening bleeding event or Grade 3 or 4 gastrointestinal/variceal bleeding event requiring transfusion, endoscopic, or surgical intervention within 3 months prior to the first dose of the study drug. 13. Hepatic encephalopathy, hepatorenal syndrome, Child-Pugh B or more severe liver cirrhosis. 14. Complete or partial intestinal obstruction present during the screening period or history of complete or partial intestinal obstruction within 3 months prior to the first dose of the study drug, or risk of bowel perforation (including but not limited to acute diverticulitis, history of intra-abdominal abscess) or history of inflammatory bowel disease or extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea. 15. Other acute or chronic diseases or laboratory abnormalities that may result in: increased risk related to participation in the study or administration of the study drug, interference with the interpretation of study results, and participants deemed ineligible for the study by the investigator. 16. Uncontrolled metabolic disorders or other non-malignant organ or systemic diseases or secondary reactions to cancer (such as leukemoid reaction, etc.), which may lead to higher medical risks and/or uncertainty in survival evaluation. 17. Neurological, psychiatric, or social conditions that: affect compliance with study requirements, significantly increase the risk of adverse events, or impair the ability of the participant to provide written informed consent. 18. History of other primary malignant tumors. 19. Known history of immunodeficiency. 20. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. 21. History of allergic reactions to the drugs used in this study. 22. Other conditions deemed unsuitable for participation in this study by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological complete response rate (pCR rate): defined as the proportion of participants who, after surgery, show complete regression of tumor cells in the primary lesion and lymph node lesions according to pathological examination. | Up to 4 years |
| Dose-limiting toxicity (DLT), to determine MTD and/or RP2D | Up to 4 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival (EFS) | Up to 4 years | Defined as the time from the first dose (randomization) to the first determination of disease progression according to RECIST v1.1, or inability to undergo surgery or need for a change in treatment due to disease progression, local recurrence after surgery or distant metastasis, or death from any cause. |
| Major pathologic response rate (MPR)：The proportion of participants with postoperative pathology showing residual tumor cells ≤10%. | Up to 2 years | — |
| Clinical downstaging rate (T and/or N downstaging)：The proportion of participants who are ypT0, ypN0, and have a downstaging in preoperative imaging clinical staging compared to baseline imaging clinical staging. | Up to 2 years | — |
| 3-year disease-free survival (3y-DFS)：Defined as the time from R0 resection to the first recorded disease recurrence, metastasis, or death from any cause. | Up to 2 years | — |
| 5-year overall survival (5y-OS)：Defined as the time from the first dose or randomization date to death from any cause. | Up to 2 years | — |
| Preoperative objective response rate (ORR) evaluated according to RECIST v1.1. | Up to 2 years | — |
| Preoperative disease control rate (DCR) evaluated according to RECIST v1.1. | Up to 2 years | — |
| Adverse Event (AE) incidence and correlation with the investigational drug | Up to 2 years | — |
| Treatment-Emergent Adverse Event (TEAE) incidence and correlation with the investigational drug. | Up to 2 years | — |
| Adverse Event of Special Interest (AESI) incidence and correlation with the investigational drug. | Up to 2 years | — |
| Serious Adverse Event (SAE) incidence and correlation with the investigational drug. | Up to 2 years | — |
| Incidence of perioperative complications and their correlation with the investigational drug. | Up to 2 years | — |
| Area under the curve of drug concentration over time for participants treated with IBI343. | Up to 2 years | — |
| Maximum concentration (Cmax) for participants treated with IBI343. | Up to 2 years | — |
| Clearance (CL) for participants treated with IBI343. | Up to 2 years | — |
| Volume of distribution (V) for participants treated with IBI343. | Up to 2 years | — |
| Half-life for participants treated with IBI343. | Up to 2 years | — |
| Positive rate of anti-drug antibodies for participants treated with IBI343. | Up to 2 years | — |
| Positive rate of neutralizing antibodies for participants treated with IBI343. | Up to 2 years | — |
| The number of participants with abnormal laboratory test results | Up to 2 years | — |
| the number of participants showing clinically significant findings during physical examination | Up to 2 years | — |
Countries
China
Contacts
CONTACTShuang Han
Outcome results
None listed