Clinical Research Directory

Feasibility of Circulating Tumor DNA Based Minimal Residual Disease-Guided Adjuvant Therapy in Locally Advanced Gastric Cancer With Neoadjuvant Treatment

For locally advanced gastric adenocarcinoma/esophagogastric junction adenocarcinoma, the currently recommended treatment strategy per clinical guidelines is radical gastrectomy combined with perioperative therapy (including chemotherapy, immunotherapy, etc.). This approach involves several cycles of neoadjuvant therapy prior to surgery, followed by the surgical procedure, and then several cycles of adjuvant therapy post-surgery. This regimen is generally considered to offer favorable efficacy, ultimately leading to improved survival outcomes for patients. However, some patients are unable to complete the prescribed postoperative adjuvant therapy due to factors such as poor physical condition after surgery or cumulative treatment toxicity. Findings from the retrospective SPACE-FLOT study preliminarily suggest that for patients with a favorable response to neoadjuvant therapy, postoperative adjuvant therapy may not confer additional survival benefit, while potentially increasing the risk of treatment-related adverse events. Therefore, the investigators aim to utilize the latest technological approaches to identify patients who could safely forgo adjuvant therapy, enabling personalized treatment decisions, reducing unnecessary treatment, and thereby maximizing patients' long-term survival benefits. To achieve this objective, the investigators have identified circulating tumor DNA (ctDNA) testing as a potential solution. ctDNA refers to DNA fragments released by tumor cells into the extracellular space (e.g., into the bloodstream). By drawing a small amount of peripheral blood and analyzing the ctDNA within, it is possible to detect minimal residual disease (MRD) that is difficult to identify through conventional imaging methods (such as CT or MRI) after treatment. MRD is considered a critical factor that may lead to tumor recurrence. Utilizing ctDNA to detect MRD enables a convenient and accurate assessment of tumor status and treatment efficacy, thereby offering the potential for personalized treatment. Colorectal cancer represents a cancer type where ctDNA testing has been applied early and is relatively mature. In the field of colorectal cancer, the GALAXY study confirmed that ctDNA positivity can effectively predict patient survival outcomes, with superior performance to other traditional indicators. The study also found that patients with postoperative ctDNA MRD positivity tended to benefit from postoperative adjuvant chemotherapy, whereas those with ctDNA MRD negativity often did not derive such benefit. Subsequently, another randomized controlled trial (the DYNAMIC study) revealed that using ctDNA MRD to guide postoperative adjuvant chemotherapy strategies could effectively reduce unnecessary chemotherapy without adversely impacting patient survival outcomes. In the field of gastric cancer, studies such as MENCA-GC, CRITICS, and PLAGAST have all demonstrated that postoperative ctDNA can effectively predict patient prognosis in the treatment model of radical gastrectomy combined with perioperative therapy. Additionally, preliminary findings from the ongoing MRD-GATE study indicate that in treatment models without preoperative neoadjuvant therapy (i.e., surgery followed by adjuvant therapy), utilizing ctDNA MRD to guide postoperative adjuvant treatment can also reduce unnecessary chemotherapy without compromising patient survival outcomes. This study focuses on patients with locally advanced gastric cancer, integrating the latest clinical research advancements, and aims to fill the research gap concerning the efficacy of using ctDNA MRD to guide adjuvant therapy within the context of radical gastrectomy combined with perioperative therapy. This holds significant importance for optimizing treatment strategies and maximizing patient benefits.

A Study of AK104 (SC) in Combination With Oxaliplatin and Capecitabine (XELOX) Versus AK104 (IV) in Combination With XELOX in Participants With Unresectable Locally Advanced or Metastatic Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma

A Study of AK104 (SC) in Combination With Oxaliplatin and Capecitabine (XELOX) Versus AK104 (IV) in Combination With XELOX in Participants With Unresectable Locally Advanced or Metastatic Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma

Factors Influencing Immunotherapy Response in dMMR/MSI-H Gastric/Gastroesophageal Junction Adenocarcinoma

dMMR/MSI-H is a key molecular subtype of gastric cancer, found in 8-22% of cases. It is typically associated with older age, female sex, distal tumor location, and intestinal histology (Lauren classification). While this subtype predicts better survival in locally advanced disease, its prognostic role in metastatic settings is less clear. Notably, dMMR/MSI-H tumors are often resistant to conventional chemotherapy. Conversely, they demonstrate exceptional sensitivity to immunotherapy. This has led to effective strategies using immune checkpoint inhibitors, either alone or combined with chemotherapy, in both neoadjuvant and advanced disease settings. However, key challenges remain. Prospective data are largely from Western populations, leaving the efficacy in Asian patients-who bear a high disease burden-less defined. Furthermore, about half of dMMR/MSI-H patients exhibit primary or acquired resistance to immunotherapy. A deeper understanding of the tumor-immune dynamics during treatment is crucial to uncover resistance mechanisms and improve patient outcomes.

Feasibility of Circulating Tumor DNA Based Minimal Residual Disease-Guided Adjuvant Therapy in Locally Advanced Gastric Cancer With Neoadjuvant Treatment: An Adaptive Trial (MRD-ATLAS)

Standard treatment for locally advanced gastric cancer currently involves surgery combined with chemotherapy administered both before and after the operation. However, post-surgery (adjuvant) chemotherapy often causes severe side effects, and it is unclear if all patients truly benefit from it. Recent research, such as the SPACE-FLOT study, suggests that patients who respond well to pre-surgery treatment might not actually benefit from further aggressive treatment after surgery; in these cases, additional therapy may only increase the risk of side effects without improving survival. To address this, researchers are investigating circulating tumor DNA (ctDNA) testing, which detects microscopic traces of cancer (Molecular Residual Disease, or MRD) in the blood. The utility of ctDNA is supported by extensive research: In Colorectal Cancer: The GALAXY study demonstrated that ctDNA status accurately predicts patient survival and identifies who benefits from chemotherapy. Furthermore, the DYNAMIC study showed that using ctDNA to guide treatment decisions significantly reduced the use of unnecessary chemotherapy without compromising patient survival. In Gastric Cancer: Studies such as MENCA-GC, CRITICS, and PLAGAST have confirmed that post-surgery ctDNA is a strong predictor of patient prognosis. Additionally, the MRD-GATE study provided preliminary evidence that ctDNA-guided strategies can reduce unnecessary chemotherapy in the adjuvant setting. Building on this evidence, this study applies ctDNA testing to the standard perioperative treatment model for gastric cancer. The primary objective is to determine if a ctDNA-guided strategy can identify patients who can safely forgo post-surgery chemotherapy, thereby reducing treatment toxicity and unnecessary usage, without sacrificing long-term survival outcomes.

Comparing the Efficacy and Safety of Different Postoperative Adjuvant Regimens in Patients With Resectable Adenocarcinoma of the Esophagogastric Junction Who Underwent Radical Surgery After Neoadjuvant Chemotherapy Combined With Immunotherapy and Achieved pCR in Postoperative Pathology

This study is to evaluate the efficacy and safety of different postoperative adjuvant regimens in patients with resectable adenocarcinoma of the esophagogastric junction who underwent radical surgery after neoadjuvant chemotherapy combined with immunotherapy and achieved pCR in postoperative pathology

Comparing the Efficacy and Safety of Chemotherapy Combined With or Without Immunotherapy as Postoperative Adjuvant Regimens in Patients With Resectable Gastric Cancer/Adenocarcinoma of the Esophagogastric Junction After Radical Surgery

This study is to evaluate the efficacy and safety of chemotherapy combined with or without immunotherapy as postoperative adjuvant regimens in patients with resectable gastric cancer/adenocarcinoma of the esophagogastric junction after radical surgery

Comparing the Efficacy and Safety of Chemotherapy Combined With or Without Immunotherapy as an Adjuvant Treatment After Radical Surgery for Patients With Resectable Adenocarcinoma of the Esophagogastric Junction of Gastric Cancer

This study is to evaluate the efficacy and safety of chemotherapy combined with or without Immunotherapy as an Adjuvant Treatment After Radical Surgery for Patients With Resectable Adenocarcinoma of the Esophagogastric Junction of Gastric Cancer

Assessing Iparomlimab and Tuvonralimab in Recurrent or Metastatic MSI-H/dMMR Gastric Cancer

A randomized controlled phase II study exploring first-line treatment options for recurrent/metastatic MSI-H gastric cancer

Pucotenlimab Combined With Chemotherapy as Perioperative Treatment for Locally Advanced Gastroesophageal Junction Carcinoma

This study is a prospective, multicenter, single-arm clinical trial. The study intends to enroll patients with pathologically or cytologically confirmed resectable locally advanced gastroesophageal junction tumors (cT2N+M0 and cT3-4bNxM0) who have not received prior systemic therapy. After signing the informed consent and being screened to meet the inclusion and exclusion criteria, patients will receive 3 cycles of Pucotenlimab combined with chemotherapy (Nab-Paclitaxel + Tegafur + Carboplatin). Preoperative imaging evaluations will be performed 3 to 6 weeks after the final dose administration to assess the efficacy of neoadjuvant therapy and the feasibility of radical resection. Efficacy evaluation will be performed after radical surgery for locally advanced gastroesophageal junction tumors.

Study of The Second-line Treatment of Advanced Gastric / Gastroesophageal Junction Adenocarcinoma With Cadonilimab and Fruquintinib Combined With Paclitaxel-albumin

This study is a prospective, open-label, two-arm exploratory Phase II clinical trial aimed at observing and evaluating the efficacy and safety of combined therapy with cadonilimab and fruquintinib in conjunction with paclitaxel-albumin as second-line treatment for advanced gastric/esophagogastric junction adenocarcinoma. Patients meeting the inclusion criteria were divided into two groups based on whether they had received PD-1/L1 antibody treatment in the first line: Group A (immunotherapy-naive group - patients who had previously failed standard chemotherapy in the first line) and Group B (immunotherapy rechallenge group - patients who had previously failed PD-1/L1 antibody combined chemotherapy in the first line). All patients received combined therapy with cadonilimab and fruquintinib in conjunction with paclitaxel-albumin until intolerable toxic reactions occurred, disease progression, withdrawal of informed consent by the subject, loss to follow-up, death, other conditions judged by the investigator to require termination of treatment, or termination of the study, whichever occurred first. The maximum duration of paclitaxel-albumin treatment was 6 cycles, and cadonilimab treatment did not exceed 1 year. Clinical tumor imaging evaluations were conducted every 8 weeks during treatment using RECIST v1.1 criteria, and safety assessments were performed using CTCAE 5.0, recording adverse events within 30 days from the first dose to the end of treatment.