Gastroesophageal Adenocarcinoma

The ZANGEA trial is a open-label, single arm, multicenter phase II trial assessing the efficacy of zanidatamab in combination with pembrolizumab and chemotherapy in patients with metastatic gastroesophageal adenocarcinoma (GEA). The patients need to be previously untreated in the palliative setting and tested positive for HER2 and PD-L1.

This is a randomized, open label, single-center, phase 2, randomized controlled trial of sequential cytoreductive intervention versus standard of care therapy for patients with intervenable oligometastatic (stage IV) cancer of the upper gastrointestinal (GI) tract and undetectable ctDNA at the time of randomization after a three-month induction chemotherapy period.

This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity of a personalized cancer vaccine strategy in patients with solid tumors and molecular residual disease. The hypothesis of the trial is that synthetic long peptide personalized cancer vaccines will be safe and capable of generating measurable neoantigen-specific T-cell responses enabling ctDNA clearance. The personalized cancer vaccines are composed of synthetic long peptides corresponding to prioritized cancer neoantigens and will be co-administered with poly-ICLC.

GEMINI-PeriOp GC study will assess the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of novel agents or novel combinations as perioperative treatment in participants with locally advanced resectable gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma who have not received previous treatment for the disease.

This study is being done to answer the following question: Can the chance of gastroesophageal cancer growing or spreading be lowered by adding a drug called zanidatamab to the usual combination of drugs? We are doing this study because we want to find out if this approach is better or worse than the usual approach for this type of cancer. The usual approach is defined as care most people get for gastroesophageal cancer

This study is evaluating the safety, side effects, how the body processes HH160, and its early anticancer activity when given alone or with other cancer treatments in participants with advanced solid tumors. The study will also identify the recommended dose for future studies. The trial includes two phases and is expected to last about 4 years, with treatment and follow-up lasting approximately 6-12 months each.

Esophageal and gastroesophageal junction cancers are serious diseases with limited cure rates, even when patients receive chemotherapy and surgery. New ways to improve treatment are urgently needed. This study will test whether adding a commonly used cholesterol-lowering medication, simvastatin, to standard cancer treatment can improve outcomes. Simvastatin is widely used, safe, and inexpensive. Research suggests that it may also slow cancer growth by blocking pathways that cancer cells rely on for survival. In this trial, patients will receive standard chemotherapy (with or without immunotherapy) before surgery. Half of the patients will also take simvastatin daily for up to two years. Researchers will compare how well tumors respond to treatment and whether patients remain cancer-free longer. If successful, this approach could offer a simple and accessible way to improve survival for patients with these cancers without adding significant side effects or cost.

This is a Phase 1, multicenter, open-label study of DISP-10, a combination therapy consisting of DV-10 (adenovirus) and idecabtagene vicleucel (ide-cel, BCMA-directed chimeric antigen receptor \[CAR\] T), in adult participants with advanced gastrointestinal (GI) cancers. The study will consist of 2 parts: dose-escalation (Part 1) and dose-expansion (Part 2). Part 1 of the study will evaluate the safety and tolerability of increasing dose levels of DISP-10 to establish the recommended dose for expansion (RDE); Part 2 will evaluate the safety and efficacy of DISP-10 in participants treated at the RDE.

This is a phase 1/2, multicenter, open-label umbrella platform study that will evaluate the safety and tolerability of investigational agents with pembrolizumab and fluoropyrimidine chemotherapy for the first-line (1L) treatment of participants with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma. This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for investigational agents in combination with chemotherapy and immunotherapy. There is no formal hypothesis in this study.

This is a phase 1/2 multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of sacituzumab tirumotecan (MK-2870) plus paclitaxel versus ramucirumab plus paclitaxel, and HER3-DXD plus ramucirumab versus ramucirumab plus paclitaxel for the treatment of participants with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, or esophageal adenocarcinoma who have failed 1 prior line of therapy. This is an estimation study, and no formal hypothesis testing will be performed.

This study is looking at how safe BHB810 is in adults with gastric and gastroesophageal adenocarcinoma (GEJ). The purpose of this study is also to look at: how well the study drug works, how the study drug moves into, through, and out of the body, and how your body reacts to the study drug. Participants will get an IV infusion of BHB810 every 2 weeks while on study treatment.

This study will test a new personalized treatment approach for patients with stomach or esophageal cancer. It will take place in two stages and aims to find the best combination of chemotherapy, immunotherapy, and targeted drugs based on each patient's tumor biomarkers. Upon enrollment onto the study, patients will consent to tumor biomarker testing and may receive one cycle of standard chemotherapy while awaiting results. Those with a matching biomarker will join the corresponding treatment group that combines chemotherapy, an immune checkpoint inhibitor, and/or a targeted therapy. In Stage I of the study, treatment lasts about four months before surgery, followed by an additional eight months of therapy for a total of one year. The most effective treatments from Stage I will be studied further in Stage II of the study to see whether some patients can safely avoid surgery. Those patients enrolled during Stage II will receive four months of the same combination treatment (chemotherapy, an immune checkpoint inhibitor, and/or a targeted therapy) but may be eligible to skip surgery if their cancer completely disappears after pre-surgery therapy. All patients will then receive an additional eight months of therapy and those who skipped surgery will be closely monitored with scans and endoscopies.

This is a phase 1b prospective, single arm, open-label trial determining the efficacy and feasibility of using a response-guided approach to help guide neoadjuvant chemotherapy in subjects with Stage IB, II or Stage III adenocarcinoma of the stomach or gastroesophageal junction (GEA).

This is a randomized, non-comparative, open-label, two-arm phase II clinical trial designed to evaluate the efficacy and safety of neoadjuvant therapy with adebrelimab plus induction chemotherapy versus adebrelimab plus SHR-8086 in patients with dMMR/MSI-H gastric or gastroesophageal junction adenocarcinoma.

A first-in-human study using BDC-4182 as a single agent in gastric and gastroesophageal cancers

TQB2102 for injection is a novel antibody-coupled drug (ADC) that enhances binding to tumor cell surface HER2 proteins by simultaneously targeting the two non-overlapping epitopes of the HER2 protein, Endothelial Cell Dysfunction 2 (ECD2) and Endothelial Cell Dysfunction 4 (ECD4), increasing HER2 internalization, and then down-regulating the tumor cell surface HER2 proteins more effectively, and doubly blocking the HER2 signaling, to achieve the effects of trastuzumab and Pertuzumab alone and in combination. This is a Phase II study to evaluate the efficacy and safety of TQB2102 for injection in combination with Benmelstobart Injection /Penpulimab Injection ± chemotherapy in patients with unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma

Gastric cancer is one of the most common and deadly cancers globally, characterized by a poor prognosis. Approximately 70% of patients are diagnosed at an advanced stage, and the 5-year survival rate is only around 10%. While advancements in targeted therapies and immunotherapy have improved treatment efficacy and extended survival, advanced gastric and gastroesophageal junction adenocarcinomas remain incurable. Subgroup analyses indicate that patients with limited metastases, such as liver oligometastasis or retroperitoneal lymph node metastasis, may benefit more from conversion therapy. However, current guidelines do not recommend specific treatment protocols for gastric cancer with limited metastasis. Immunotherapy has shown moderate efficacy in selected patients with advanced gastric adenocarcinoma. Additionally, low-dose radiotherapy (LDRT) may synergistically enhance antitumor responses when combined with immunotherapy. This Phase II trial aims to evaluate the safety and efficacy of combining Adebrelimab, chemotherapy, and LDRT before surgery in treating adult patients with gastric or gastroesophageal junction adenocarcinoma.

The addition of immunotherapy to chemotherapy improves outcomes in patients with HER2-negative gastroesophageal adenocarcinoma (GEA), and investigators aim to explore its role in the perioperative setting. Moreover, optimizing the timing schedule of these two therapies is critical when balancing efficacy and safety. This Chinese, multicenter, open-label phase 1b/2 trial will evaluate the efficacy and toxicity of perioperative folinic acid, fluoro-uracil, oxali-platin (FOLFOX), and toripalimab (JS001, a novel PD-1 inhibitor) in combination at various schedules in the neoadjuvant setting in patients with HER2-negative resectable GEA: three cycles each in Arm A: FOLFOX (D1, q2w) followed by toripalimab (D3, 3 mg/kg, q2w); Arm B: concurrent FOLFOX (D1, q2w) combined with toripalimab (D1, 3 mg/kg, q2w); Arm C: toripalimab (D1, 3 mg/kg, q2w) followed by FOLFOX (D3, q2w); Arm D: FOLFOX (D1, q2w) alone. The primary end-point is the dose-limiting toxicity in Phase 1b and the pathological complete response rate in Phase 2; secondary end-points include major pathologic response, disease-free survival, and event-free survival.A fixed sample size of 126 patients is used in this study, with a safety run-in period (n = 6) and cohort expansion period (n = 24), a dropout rate of 5% within 12 months of follow-up. Each arm receives three cycles of FOLFOX (D1, q2w) followed by 15 cycles of toripalimab (D1, 240 mg, q3w) in the neoadjuvant setting. Pre-treatment biopsies, post-resection specimens, serial liquid biopsy, and gut microbiota samples on treatment will be collected to explore the biomarkers' predictive value on diverse schedule efficacy and safety.