NCT05594381

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

A Prospective, Open-label, Single-Arm, Phase II Study on Biomarkers for Predicting the Efficacy of Neoadjuvant Sintilimab in Combination With Tegafur and Oxaliplatin (SOX) for cStage III Gastric or Gastroesophageal Junction Adenocarcinoma.

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: The First Affiliated Hospital with Nanjing Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

At present, radical surgery is still the only way to cure Gastric Cancer（GC）, but the surgical resection rate is low, and the R0 resection rate is about 70-80%. The postoperative recurrence rate of patients with stage II and above is high. To improve the surgical resection rate, seek more effective treatment. The other treatment therapeutics are the direction of development of GC treatment research. Neoadjuvant therapy for GC can reduce tumor stage and increase the likelihood of complete tumor resection to achieve maximum pathological response. Neoadjuvant chemotherapy followed with surgery has been written into the NCCN guidelines for GC. Since China, the United States and Japan successively approved PD-1 monoclonal antibody for the treatment of unresectable and/or metastatic GC and gastroesophageal junction adenocarcinoma (G/GEJ adenocarcinoma), a number of clinical studies about the therapeutic effects of PD-1 antibodies combined with chemotherapy as preoperative neoadjuvant therapy are carring out worldwide. A single-arm phase II clinical study has demonstrated that the Sintilimab,which is the only one PD-1 mAb that has the indication for first-line treatment of GC in China, combined with oxaliplatin and capecitabine in neoadjuvant treatment of locally advance resectable GC. The treatment showed encouraging pCR rates and a good safety profile. However, how to select suitable patients for neoadjuvant immunotherapy is the focus of current research. Indicators such as PD-L1 expression, tumor mutation burden, and microsatellite stability are currently considered to be the average indicators of the efficacy of PD-1/PD-L1 monoclonal antibody therapy. However, according to the NCCN guidelines, these biomarkers are mainly used in patients with advanced postoperative tumors, and the conclusions obtained in different studies such as KEYNOTE-061 and KEYNOTE-062 are still partially contradictory, failing to accurately guide the treatment. Therefore, it is urgent to explore highly sensitive and specific indicators that can be used to monitor the efficacy of neoadjuvant immunotherapy for GC. This study intends to dynamically detect gene mutations, protein expressions and tumor images in G/GEJ tumor tissues and blood samples before, under and after neoadjuvant therapy by using ctDNA targeted sequencing combined with multi-omics technology. Through independent and association analysis and building risk models, biomarkers with significant predictive effects on the curative effect of neoadjuvant immunotherapy were found, so as to identify the suitable population for neoadjuvant immunotherapy for locally advanced and resectable G/GEJ adenocarcinoma.

Conditions

• Gastric Cancer

Interventions

Type	Name	Description
DRUG	Sintilimab	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).

Timeline

• Start date: 2022-10-01
• Primary completion: 2023-09-01
• Completion: 2025-10-01
• First posted: 2022-10-26
• Last updated: 2022-10-26