A Biomarker Study for Predicting the Efficacy of Neoadjuvant Sintilimab Plus SOX for Gastric Adenocarcinoma.

NCT05594381 | Unknown Phase 2

• 1 other identifier: JSGCLB-2201
• Study Type: interventional
• Target: 90
• Locations: 0 countries
• Sites: N/A

Brief Summary

Recently, a number of clinical studies were carried out to evaluate the therapeutic effects of PD-1 antibodies combined with chemotherapy as preoperative neoadjuvant therapy of gastric cancer (GC) worldwide. Indicators such as PD-L1 expression, TMB and MSI are currently used to evaluate the efficacy of PD-1/PD-L1 monoclonal antibody therapy. However, these biomarkers are mainly used in patients with metastatic and unresectable tumors, and the conclusions obtained in different studies are still partially contradictory, failing to accurately guide the treatment. Therefore, it is urgent to explore highly sensitive and specific biomarkers that can be used to monitor the efficacy of neoadjuvant immunotherapy for GC.The present clinical trial aims to use ctDNA dynamic monitoring combined with multi-omics methods to evaluate PD-1 monoclonal antibody (sintilimab) combined with SOX neoadjuvant therapy for clinical stage III gastric/gastroesophageal junction adenocarcinoma. In order to identify the suitable population for neoadjuvant immunotherapy for locally advanced and resectable G/GEJ adenocarcinoma.

Conditions

Gastric Cancer

Keywords

Gastric Cancer with cStage III; Circulating tumor DNA; Neoadjuvant immunotherapy plus chemotherapy; Evaluation biomarkers

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate (pCR)

  pCR rate is the proportion of patients who have no residual viable tumor in the resected specimens. The primary aim of the study is to test the hypothesis that after neoadjuvant therapy，patients with ctDNA clearance result in a higher rate of pCR.

  an average of 6 months.

Secondary Outcomes (10)

• Objective Response Rate (ORR)

  an average of 4 months.

• Disease Control Rate (DCR)

  an average of 4 months.

• Major pathological response rate (MPR)

  after surgery，an average of 6 months.

• Tumor Regression Grade (TRG)

  an average of 6 months.

• R0 resection rate

  an average of 6 months.

Other Outcomes (2)

• Relationship between the numerical changes of ctDNA during neoadjuvant immunotherapy plus chemotherapy and postoperative pathological remission rate

  an average of 6 months.

• Genomic changes of ctDNA

  an average of 6 months.

Study Arms (1)

Neoadjuvant Sintilimab plus SOX therapy

EXPERIMENTAL

All enrolled subjects were treated with Sintilimab combined with SOX regimen (Oxaliplatin plus Tegafur) for 3 cycles and then underwent radical surgery. Peripheral blood from all patients will be collected at the following 5 time points: before neoadjuvant therapy (within 3 days before the first dose); before the start of the third cycle of neoadjuvant therapy (within 3 days); before surgery (within 7 days) and after surgery (within 3-7 days). Plasma was tested for ctDNA. All subjects were further stratified according to the detection results of ctDNA and their changes during the neoadjuvant treatment period. After operation, sintilimab combined with SOX therapy was continued for 5 cycles according to the original plan (if the preoperative treatment did not reach 3 cycles, it should be supplemented to 8 cycles)

Drug: Sintilimab

Interventions

Sintilimab DRUG

Neoadjuvant treatment method: Sintilimab 200 mg, i.v., d1 + oxaliplatin 130 mg/m2, d1, i.v., + Tegafur 40 mg po, bid, d1-14; 3-week course; Neoadjuvant therapy: 3 courses of preoperative SOX chemotherapy (oxaliplatin+Tegafur) + PD-1 monoclonal antibody (Sintilimab). After the 2nd and 3rd cycles of neoadjuvant therapy (6-9 weeks from the start of treatment), imaging effects and feasibility of radical surgery were performed respectively; The operation time is arranged within 2-6 weeks after the last administration of neoadjuvant therapy, and the operation method is selected by the surgeon according to the actual needs; The postoperative treatment plan is the same as the preoperative neoadjuvant treatment plan, and the SOX+Sintilimab will continue to be given until the full 8 cycles (including the preoperative 3 cycles).

Also known as: Oxaliplatin, Tegafur, Radical gastrectomy with D2 lymph node dissection

Neoadjuvant Sintilimab plus SOX therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• G/GEJ adenocarcinoma patients aged 18-75 years old, male or female;
• Patients with cStage III by abdominal CT and intraoperative assessment, and G/GEJ adenocarcinoma diagnosed by gastroscope and pathology (regardless of HER-2 expression), and gastroesophageal junction (GEJ) cancer only allows Siewert III Type II, and Siewert type II subjects who did not require combined thoracotomy were enrolled.
• Before enrollment, a gastrointestinal surgeon and an imaging technologist will jointly evaluate the tumor as cStage III and be eligible for R0 resection for the purpose of cure;
• The initial diagnosis has not been treated;
• Expected survival period ≥ 3 months;
• According to the RECIST v1.1 criteria (see Annex 3 for details), there are measurable tumor lesions;
• The ECOG PS score within 7 days of the first medication (see Annex 4 for details) is 0-1;
• The heart function is good, and resection for curative purpose can be performed. Patients with underlying ischemic, valvular, or other serious cardiac disease should be evaluated preoperatively by a cardiologist if clinically indicated;
• Those who have used anti-tumor traditional Chinese medicines, proprietary Chinese medicines, and immunomodulators (such as thymosin, lentinan, interleukin-12, etc.) must be ≥ 2 weeks away from the start of the study medication.
• To have sufficient organ function, subjects must meet the following laboratory indicators:1) The absolute value of neutrophils (ANC) is ≥1.5x109/L without the use of granulocyte colony-stimulating factor in the past 14 days; 2) Platelets ≥100×109/L without blood transfusion in the past 14 days; 3) Hemoglobin\>9g/dL without blood transfusion or use of erythropoietin in the past 14 days; 4) Total bilirubin≤1.5×ULN; if total bilirubin\>1.5×ULN but direct bilirubin≤ULN, it is also allowed to enter the group; 5) Aspartate aminotransferase (AST), alanine aminotransferase (ALT) in ≤2.5×ULN; 6) Serum creatinine ≤1.5×ULN and creatinine clearance rate (calculated by Cockcroft-Gault formula) ≥60 ml/min; 7) Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; 8) Normal thyroid function, defined as Thyroid Stimulating Hormone (TSH) within the normal range. If the baseline TSH exceeds the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled; 9) Myocardial enzyme spectrum is within the normal range (if the investigator comprehensively judges that the simple laboratory abnormality does not have clinical significance, it is also allowed to enter the group);
• Thyroid function indicators: Thyroid-stimulating hormone (TSH), free thyroxine (FT3/FT4) in the normal range or mild and no clinically significant abnormalities;
• Weight above 40 kg (including 40 kg), or BMI\>18.5;
• Female patients must meet:
• Menopausal (defined as the absence of menstruation for at least 1 year and no other confirmed cause other than menopause) status, or who have undergone surgical sterilization (removal of ovaries and/or uterus), or are fertile patients must meet both of the following requirements:
• Serum pregnancy test results must be negative within 7 days prior to the first dose;

You may not qualify if:

• The patient has other malignant tumors in the past (within 5 years) or at the same time. Cured localized tumors, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, carcinoma in situ of the breast, stage I lung cancer, stage I colorectal cancer, etc. ;
• Patients who are going to undergo or have received organ or bone marrow transplantation in the past;
• Have undergone blood transfusion within 2 weeks before the first drug, or have a history of bleeding, and have any bleeding event with a severe grade of CTCAE4.0 grade 3 or above within 4 weeks before screening;
• Patients with abnormal coagulation function and bleeding tendency (INR is \>1.5 in the absence of anticoagulants); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogs ; On the premise of prothrombin time international normalized ratio (INR) ≤ 1.5, low-dose warfarin (1 mg orally, once a day) or low-dose aspirin (no more than 100 mg per day) is allowed for prophylaxis. ;
• Arterial/venous thrombosis events occurred within 6 months before screening, such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis (venous thrombosis caused by venous intubation due to previous chemotherapy and has been cured by the investigator's judgment excluding those) and pulmonary embolism, etc.;
• Myocardial infarction and poorly controlled arrhythmia (including QTc interval ≥ 450 ms for men and ≥ 470 ms for women) within 6 months before the first medication (QTc interval is calculated by Fridericia formula);
• The presence of NYHA standard III to IV cardiac insufficiency or cardiac ultrasound examination: LVEF (left ventricular ejection fraction) \<50%;
• Urine routine indicates urine protein ≥++ and confirmed 24-hour urine protein quantification \>1.0 g;
• There are multiple factors that affect oral drugs (such as inability to swallow, chronic diarrhea and intestinal obstruction, etc.);
• Pleural effusion or ascites with clinical symptoms requiring clinical intervention;
• Human immunodeficiency virus (HIV) infection;
• Suffering from active pulmonary tuberculosis;
• Long-term unhealed wounds or incompletely healed fractures;
• Patients with past and current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severely impaired lung function, etc., which may interfere with the detection and treatment of suspected drug-related pulmonary toxicity;
• There is a known active or suspected autoimmune disease, except those who are in a stable state of the disease at the time of enrollment (systemic immunosuppressive therapy is not required);

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator
• Nanjing Geneseeq Technology Inc.: collaborator

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

sintilimab; Oxaliplatin; Tegafur

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Fluorouracil; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Zekuan Xu, PhD

  The First Affiliated Hospital with Nanjing Medical University

  STUDY CHAIR

Central Study Contacts

Bowen Li, PhD

CONTACT

+86-025-6830-6861; lbwlbwlbwlbw@126.com

Fengyuan Li, PhD

CONTACT

+8617366065271; 491275128@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2022
• First Posted: October 26, 2022
• Study Start: October 1, 2022
• Primary Completion: September 1, 2023
• Study Completion: October 1, 2025
• Last Updated: October 26, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share