Immunotherapy, Gastric Cancer (GC), Radiotherapy, Neoadjuvant Therapy, Neoadjuvant Chemoimmunotherapy
Conditions
Keywords
Immunotherapy, Gastric Cancer, Radiotherapy, Neoadjuvant therapy, Neoadjuvant Chemoimmunotherapy
Brief summary
Neoadjuvant radiotherapy plus Tegafur, Oxaliplatin and Iparomlimab and Tuvonralimab in Resectable Gastric and GE-junction Cancer : A Randomized, Two-arm, Prospective Trial (TRIUNITE-05)
Detailed description
TRIUNITE-05 is a randomized, two-arm, uncontrolled, prospective study to evaluate the efficacy and safety of neoadjuvant radiotherapy combined with immunochemotherapy for locally advanced G/GEJ adenocarcinoma. This study will include subjects with locally progressive G/GEJ adenocarcinoma, patients in Group A will be treated with radiotherapy (30Gy/10f) followed by sequential SOX regimen in combination with Iparomlimab and Tuvonralimab (5 mg/kg, i.v.) for 6 cycles of induction therapy, with full evaluation and surgery 4-6 weeks after the end of the treatment; patients in group B will be treated with SOX regimen in combination with Iparomlimab and Tuvonralimab for 3 cycles of induction therapy followed by sequential radiotherapy ( 30Gy/10f) followed by 3 cycles of sequential SOX regimen combined with Iparomlimab and Tuvonralimab (5 mg/kg, i.v.), with full evaluation and surgery 4\ 6 weeks after the end of treatment. For those who were assessed to be inoperable after neoadjuvant therapy, the original regimen of immunotherapy in combination with chemotherapy was concurrently administered until progression; if it was ineffective, the regimen was changed to a second-line chemotherapy regimen or other anti-tumor combination therapy regimens were considered as appropriate. Patients were then entered into long-term survival follow-up. During the study period, preoperative and postoperative blood, feces, and pathological tissues of subjects were collected for testing biomarkers to explore the potential benefit population of neoadjuvant therapy. Blood and fresh tissues were subjected to single-cell sequencing, spatial transcriptomic or proteomic analysis, and tissues were subjected to multiplex immunofluorescence assay, in order to further search for potential biomarkers that may be beneficial for the benefit of neoadjuvant therapy in locally advanced gastric cancer.
Interventions
q3w Iparomlimab and Tuvonralimab 5mg/kg on day 1 of each cycle
DRUGOxaliplatin
130mg/m2 on day 1 of each cycle
DRUGTegafur
\<1.25 m2, 40 mg; 1.25 to ≤1.5 m2, 50 mg; and ≥ 1.5 m2, 60 mg；po；d1-14 bid
RADIATIONRadiotherapy
30 Gy/10 fractions
Sponsors
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The patients are able to understand and voluntarily sign the written informed consent, which must be signed prior to the implementation of the designated research procedures required by the study. * The age at the time of signing the informed consent form (ICF) is ≥ 18 years old, both male and female. * Histologically confirmed to have HER2-negative gastric or gastroesophageal junction adenocarcinoma (Siewert type II or Siewert type III with ≤2 cm of esophageal involvement) with AJCC 8th edition staging of Stage IIA- Stage III, i.e., T1- 2N+, and T3-4 and or N+, and resectable;. * The patients are willing to provide fresh blood, feces, and tumor tissue for biomarker analysis, and the tissue samples provided are of sufficient quality to evaluate the status of biomarkers. If sufficient tissue is not provided, repeated sampling may be required. * The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1. * The expected survival time was ≥ 3 months.\\ * No previous anti-tumor therapy (including chemotherapy, radiotherapy, targeted therapy, immunotherapy, interventional therapy, and traditional Chinese medicine with clear anti-tumor effects, excluding abdominal exploration for diagnostic staging); * The patient has adequate organs function 1. The patient has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥1.5\*10\^9/L, hemoglobin ≥90g/L (5.58 mmol/L), and platelets ≥100\*10\^9/L. 2. The patient has adequate renal function as defined by a serum creatinine ≤1.5 times the ULN, or creatinine clearance (measured via 24-hour urine collection) ≥50 mL/minute (that is, if serum creatinine is \>1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed). 3. The patient has adequate hepatic function as defined by a total bilirubin ≤1.5 mg/dL (25.65 μmol/L), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times the upper limit of normal (ULN; or 5.0 times the ULN in the setting of liver metastases). 4. The patient must have adequate coagulation function as defined by international normalized ratio (INR) ≤1.5 * Within 7 days before the first administration, women of childbearing age must confirm that the serum pregnancy test is negative and agree to use effective contraceptives during the study period and within 180 days after the last administration. In this program, women of childbearing age are defined as sexually mature women: 1. No hysterectomy or bilateral ovariectomy 2. Natural menopause does not last for 24 months (amenorrhea after cancer treatment does not rule out fertility) (that is, menstruation occurs at any time in the previous 24 months). For male patients whose sexual partners are women of childbearing age, they must agree to use effective contraception during the study drug use and within 180 days after the last administration.
Exclusion criteria
* Palliative local treatment was given to non-target lesions within 2 weeks before the first administration, and systemic non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, etc.) was received within 2 weeks before the first administration. Chinese herbal medicine or proprietary Chinese medicine with anti-tumor indications was received within 2 weeks before the first administration. * The patient has previously received immune checkpoint inhibitors (such as anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint agonists (such as antibodies against ICOS, CD40, CD137, GITR, OX40 targets, etc.), immune cell therapy, etc. any treatment aimed at the immune mechanism of tumor. * There was a history of gastrointestinal perforation and gastrointestinal fistula within 6 months before the first administration. If the perforation or fistula has been removed or repaired, and the disease has been judged by the researchers to recover or remission, it may be allowed to join the group. * Active or previously recorded inflammatory bowel disease (such as Crohn's disease or ulcerative colitis). Unable to swallow, malabsorption syndrome, or uncontrollable nausea, vomiting, diarrhea or other gastrointestinal diseases that seriously affect drug use and absorption. * There were active malignant tumors in the past 3 years, except for tumors that participated in the study and local tumors that had been cured. such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, breast cancer in situ, localized prostate cancer and so on. * Active or untreated brain metastases, meningeal metastases, spinal cord compression or leptomeningeal diseases are known. However, the patients who met the following requirements and had measurable lesions outside the central nervous system were allowed to enter the group: asymptomatic after treatment, imaging was stable for at least 4 weeks before the start of treatment (such as no new or enlarged brain metastases). And systemic corticosteroids and anticonvulsant drugs have been stopped for at least 2 weeks. * There are pleural effusion with clinical symptoms, pericardial effusion or ascites requiring frequent drainage (≥ 1 / month). * Study active autoimmune diseases that require systematic treatment within 2 years before the start of treatment, or researchers determine the existence of autoimmune diseases that may recur or plan treatment. Except for the following: 1. Skin diseases that do not require systematic treatment (e.g. vitiligo, hair loss, psoriasis or eczema) 2. Hypothyroidism caused by autoimmune thyroiditis requires only a stable dose of hormone replacement therapy. 3. Type I diabetes mellitus requiring only a stable dose of insulin replacement therapy 4. Asthma has been completely relieved in childhood and no intervention is needed in adults. 5. The researchers determined that the disease would not recur without external triggers. * There are any of the following cardio-cerebrovascular diseases or cardio-cerebrovascular risk factors: 1. Within 6 months before the first administration, there were myocardial infarction, unstable angina pectoris, cerebrovascular accident, transient ischemic attack, acute or persistent myocardial ischemia, symptomatic heart failure (according to New York Heart Association functional grade 2 or above), symptomatic or poorly controlled arrhythmia, or any arterial thromboembolic event. 2. There was a history of deep venous thrombosis, pulmonary embolism or other severe thromboembolism within 3 months before the first administration. 3. There are major vascular diseases, such as aortic aneurysm, aortic dissecting aneurysm, internal carotid artery stenosis, which may be life-threatening or require surgery within 6 months. 4. Previous history of myocarditis and cardiomyopathy. 5. Left ventricular ejection fraction (LVEF) \< 50%. * Toxicity that has not been alleviated by previous antineoplastic therapy is defined as undiminished to Grade 0 or 1 of the National Cancer Institute (NCI) General terminology Standard for adverse events (CTCAE) (NCICTCAEv5.0), or to the level specified in the selection /
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological Complete Response (pCR) | 8 months |
Secondary
| Measure | Time frame |
|---|---|
| Disease Control Rate (DCR) | 7 months |
| Progression Free Survival (PFS) | 3 years |
| Overall Survival (OS) | 3 years |
| Clinical Complete Response (cCR) | 7 months |
| Major Pathologic Response (MPR) | 8 months |
| Objective Response Rate (ORR) | 7 months |
Other
| Measure | Time frame |
|---|---|
| Correlation analysis of evaluating the relationship between multi-omics analysis of tumor tissue and neoadjuvant immunochemotherapy efficacy | 3 years |
| Adverse events (AE) | 6 months |
| Correlation analysis of evaluating the relationship between clinicopathological characteristics and neoadjuvant immunochemotherapy and radiotherapy | 3 years |
Countries
China
Contacts
Primary ContactBin Wang
Outcome results
None listed