Gastroesophageal Junction Cancer

The NOMAD-GI study is a single-center, bidirectional cohort study designed to evaluate the safety and efficacy of molecular biomarker-guided non-operative management (NOM) and organ preservation strategies after precision therapy in patients with gastrointestinal cancers. Patients with actionable molecular biomarkers, including dMMR/MSI-H, POLE mutation, PD-L1 high expression, tumor mutational burden-high (TMB-H), Epstein-Barr virus positivity (EBV+), HER2 positivity, CLDN18.2 positivity, and other actionable genomic alterations, will be enrolled. After immune checkpoint inhibitor or targeted therapy, patients achieving favorable clinical responses will undergo multidisciplinary team (MDT) evaluation and receive either non-operative management, local treatment, or radical surgery according to individualized treatment decisions. The study aims to establish a molecular-driven organ preservation paradigm for gastrointestinal cancers and evaluate whether NOM can provide comparable oncological outcomes while improving functional outcomes and quality of life.

This study is being done to learn more about a new medicine called PF-08634404 and how well it works when given with chemotherapy to people with gastroesophageal cancer that is locally advanced (spread to nearby tissues) or has spread to other parts of the body. To join the study, participants must meet the following conditions: Be 18 years or older. Have locally advanced or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma Be treatment naïve for advanced or metastatic disease Be in good physical condition and have healthy organs based on medical tests. The study has two parts: * In the first part, researchers will check how safe the study medicine in combination with chemotherapy is and how well people respond to it. * In the second part, they will compare study medicine plus chemotherapy to another approved treatment (nivolumab plus chemotherapy) to see which works better. The treatment will be given in repeated time periods called cycles.

This clinical trial is designed to assess the efficacy and safety of the triplet combination of trastuzumab deruxtecan (ENHERTU, T-DXd, DS-8201a) plus a fluoropyrimidine plus pembrolizumab versus standard of care (SoC) chemotherapy plus trastuzumab plus pembrolizumab as first-line therapy in participants with unresectable, locally advanced or metastatic HER2-positive tumor PD-L1 CPS ≥1 gastric or GEJ cancer in the Main Cohort. An Exploratory Cohort will also be evaluated to assess the efficacy and safety of T-DXd plus a fluoropyrimidine versus SoC chemotherapy plus trastuzumab in participants with unresectable, locally advanced or metastatic HER2-positive tumor PD-L1 CPS \<1 gastric or GEJ cancer.

The purpose of this study is to assess the safety, tolerability, efficacy, pharmacokinetics (PK), and immunogenicity of AZD0901 as monotherapy and in combination with anti-cancer agents in participants with locally advanced unresectable or metastatic solid tumours expressing CLDN18.2.

This is a Phase 1/2 open-label, multi-center, multi-national study with an initial dose escalation part to determine the recommended Phase II dose (RP2D) of MCLA-158 single agent in patients with mCRC. The dose escalation part has been completed and the RP2D will be further evaluated in an expansion part of the study. Cohorts of selected solid tumor indications for which there is evidence of EGFR dependency and potential sensitivity to EGFR inhibition will be evaluated including head and neck cancer and metastatic colorectal cancer (mCRC). The study will further assess the safety, tolerability, PK, PD, immunogenicity, and anti-tumor activity of MCLA-158 in monotherapy or in combination with other therapies.

The objective of this study is to evaluate the safety, tolerability, and efficacy of BL-M07D1 in patients with HER2 expressing advanced tumors.

Perioperative chemotherapy (CHT) or CHT/RT combined with surgery is the standard therapeutic approach for the treatment of locally advanced cancer of the esophagus, gastroesophageal junction (GEJ), and stomach. Comprehensive cancer treatment is associated with high perioperative morbidity and mortality. Serious postoperative complications occur in up to 20-80% of patients undergoing esophagectomy. The impact of nutritional status and overall physical condition on surgical outcomes and overall treatment has been demonstrated many times. The concept of pre-rehabilitation/pre-optimization, which involves establishing an individualized nutritional plan, monitoring and managing physical activity, and providing comprehensive supportive oncological and psychological care as early as during neoadjuvant CHT or CHT/RT, is a prerequisite for improving perioperative and 30-day postoperative morbidity and mortality.

The purpose of this study is to find out whether adding cadonilimab to the usual chemotherapy approach is an effective and safe treatment for participants with locally advanced/resectable gastric cancer or gastroesophageal junction (GEJ) cancer

The purpose of this registry study is to create a database-a collection of information-for better understanding standard treatments for esophageal and Gastroesophageal Junction Cancer/GEJ cancer. Researchers will use the information from this database to learn more about the effectiveness of different treatment options.

This study will evaluate the recommended dose for further clinical development, safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and pharmacodynamics of IKS014, a HER2 targeting antibody-drug conjugate, in patients with advanced solid tumors.

The purpose of this study is to use Claudin 18.2 (CLDN18.2)-targeted positron emission tomography (PET) imaging technology to evaluate its detection efficacy and diagnostic threshold for CLDN18.2-positive pancreatic cancer and gastric/gastroesophageal junction cancer, analyze the quantitative value of PET parameters in CLDN18.2 expression and their correlation with prognosis, and provide a basis for the precise selection of CLDN18.2-targeted therapy.

This is a phase I trial of CA-4948 in combination with FOLFOX/PD-1 inhibitor with or without trastuzumab for unresectable gastric, GEJ, and esophageal cancer. During the Dose Escalation portion of the study, different dose levels of CA-4948 in combination with FOLFOX/nivolumab will be evaluated by BOIN algorithm. Dose Expansion will include Cohorts A and B. Expansion Cohort A will enroll up to 12 patients with HER2 negative gastric, GEJ, and esophageal cancer at the expansion dose of CA-4948 determined during Dose Escalation and will use the same treatment regimen of FOLFOX/nivolumab. Expansion Cohort B will investigate CA-4948 at the dose determined during Dose Escalation in combination with FOLFOX/pembrolizumab and trastuzumab in up to 12 patients with HER2 positive disease; however, the initial 6 patients will be considered safety lead-in to confirm the safety and tolerability of this combination; if determined to be safe, an additional 6 patients will be enrolled for a total of 12 in Cohort B.

This multicenter prospective randomized clinical trial aims to compare the safety and oncological effectiveness of proximal gastrectomy and total gastrectomy in patients with locally advanced Siewert type II-III gastroesophageal junction cancer. Eligible patients will be randomly assigned to undergo either proximal gastrectomy or total gastrectomy using open, laparoscopic, or robotic surgical approaches according to clinical suitability. The primary outcome of the study is 3-year disease-free survival. Secondary outcomes include postoperative mortality, postoperative complications, and the number of metastatic lymph nodes retrieved. Patients will be followed for up to five years after surgery to evaluate long-term oncological outcomes.

This is a double-blind, randomized, multiregion, comparative phase Ⅲ clinical study designed to evaluate the efficacy and safety of HLX22 in combination with trastuzumab and chemotherapy as first-line treatment in patients with HER2-positive locally advanced/metastatic adenocarcinoma of the gastric and/or gastroesophageal junction (G/GEJ).Eligible subjects will be randomized to the two groups based on a 1:1 ratio. Enrolled subjects shall be treated with the study drug until the loss of clinical benefit, death, intolerable toxicity, withdrawal of informed consent, or other reasons specified by the protocol (whichever occurs first).

This is a multi-cohort, multi-center Phase II clinical study exploring the efficacy of treatment with either Adebrelimab plus SHR-A1811/SHR-A1904 and chemotherapy, or Adebrelimab plus SHR-8068 in patients with gastric or gastroesophageal junction (GEJ) cancer. The study also evaluates the safety and tolerability of these combination regimens.

A phase 1a/1b, multicenter, open-label, dose escalation/expansion, multiple-dose study to evaluate the safety and activity of DR-0202 in patients with locally advanced or metastatic, relapsed or refractory carcinomas

The goal of this Phase II clinical trial is to evaluate the efficacy and safety of Iparomlimab and Tuvonralimab (QL1706) combined with SOX chemotherapy (S-1 plus Oxaliplatin) in patients with previously untreated advanced or metastatic gastric cancer or gastroesophageal junction cancer. The main questions it aims to answer are: 1、What is the objective response rate (ORR) of the combination of QL1706 and SOX chemotherapy? 2、What are the safety and tolerability of this combination therapy? Participants will： 1. Receive Iparomlimab and Tuvonralimab (QL1706) via intravenous infusion every 3 weeks. 2. Receive SOX chemotherapy (Oxaliplatin via intravenous infusion on Day 1 and S-1 orally twice daily for 14 days) every 3 weeks for up to 6 cycles. 3. Continue maintenance therapy with QL1706 combined with S-1 after 6 cycles until disease progression or unacceptable toxicity. 4. Undergo tumor imaging assessments (CT or MRI) every 6 weeks for the first 24 weeks, and then every 9 weeks thereafter to monitor the disease.

Gastric/GEJ adenocarcinomas are aggressive tumors with a high probability of death. Current treatment guidelines include two-drug cytotoxic chemotherapy with a fluoropyrimidine (mFOLFOX6: capecitabine or fluorouracil) and a platinum-based agent (CapOx: oxaliplatin or cisplatin). In addition, the FDA has approved nivolumab, a PD-1 checkpoint inhibitor, in combination with chemotherapy as first line treatment for advanced or metastatic gastric/GEJ cancer. TST001 is a recombinant humanized monoclonal antibody against Claudin 18.2 (a tumor marker found in gastric/GEJ cancer. In this study, the combination therapy of chemotherapy or chemotherapy and pembrolizumab with and without TST001 could provide additional benefits to the management of these tumors.

This clinical trial is evaluating a new, function-preserving surgical technique for patients with early-stage cancer in the upper part of the stomach. The current standard treatment is a Laparoscopic Total Gastrectomy (LTG), which involves the complete removal of the stomach. This study compares the standard LTG with an innovative procedure called Laparoscopic Proximal Gastrectomy combined with a novel anti-reflux reconstruction (LPG-tbROSF). This new technique removes only the cancerous upper portion of the stomach, aiming to preserve digestive functions and reduce post-surgery complications like acid reflux. The main goal is to see if patients who receive the new, stomach-preserving surgery experience less body weight loss one year after the procedure compared to those who undergo the standard total gastrectomy. The research will also compare the two surgeries in terms of post-operative quality of life, nutritional status, acid reflux symptoms, safety, and long-term cancer outcomes. The study is a multi-center, prospective, randomized controlled trial that plans to enroll 120 patients with localized cancer in the upper stomach.

At present, surgery is still the main treatment for gastroesophageal junction cancer. At the same time, multimodal comprehensive treatment such as chemotherapy and molecular targeted therapy can effectively alleviate pathological progression, facilitate R0 resection and improve the overall survival of patients.Pembrolizumab, as a PD-1 inhibitor, has been shown to have antitumor activity and a manageable safety profile in gastroesophageal junction cancer.Pembrolizumab combined with chemotherapy has become a research hotspot. However, to date, there is no clinical study related to gastroesophageal junction cancer. In this study, Pembrolizumab combined with FLOT was used as the first-line treatment for gastroesophageal junction cancer, aiming to explore the experience chemotherapy mode for gastroesophageal junction cancer.

The goal of this clinical trial is to evaluate the efficacy and safety of radiotherapy combined with chemotherapy and anti-PD-1 immunotherapy followed by surgery for the primary and metastatic lesions in patients with limited metastatic gastric or gastroesophageal junction adenocarcinoma. The main questions it aims to answer are: 1) If the multimodal treatment which includes anti-PD-1 immunotherapy and local therapies will improve the survival of this group of patients. 2) If the multimodal treatment which includes anti-PD-1 immunotherapy and local therapies can be performed safely in this group of patients. Participants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.

This is an open label, randomized, phase Ⅱ, multi-cohort study to treat subjects with ctDNA Positive Gastric and Esophagogastric Junction Adenocarcinoma. The patients will be randomized into two arms consist of Penpulimab + Anlotinib (3 weeks/cycle) + XELOX and XELOX at a ratio of 1:1. This study is conducted to assess safety and anti-tumor activity of the monoclonal antibody Penpulimab in combination with Anlotinib and standard chemotherapy as adjuvant treatment for ctDNA-positive Gastric, or Gastroesophageal Junction Carcinoma.

The purpose of this study is to evaluate the efficacy of Tislelizumab in the neoadjuvant (prior to surgery) or adjuvant (after surgery) treatment of previously untreated adults with gastric and gastroesophageal junction (GEJ) adenocarcinoma. The primary study hypotheses are that: Neoadjuvant and adjuvant Tislelizumab plus chemoradiotherapy, followed by adjuvant Tislelizumab and chemotherapy is superior to neoadjuvant chemoradiotherapy or chemotherapy, followed by adjuvant chemotherapy in terms of rate of Pathological Complete Response (pathCR) at the time of surgery.

To observe and determine the safety, tolerability, cellular pharmacokinetics and efficacy of TCRx T cells in patients with advanced or recurrent gastric/gastroesophageal junction cancer after failure of first chemotherapy.

Purpose of this study is to define the maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D) of paclitaxel and tepotinib combination therapy in patients with advanced tumors and to evaluate the efficacy of paclitaxel and tepotinib combination treatment as second-line therapy in patients with advanced gastric and gastroesophageal junction carcinomas (AGC/GEJCs) with MET amplification or MET exon 14 alterations. This study is devided into Phase 1b and Phase 2 study.