Clinical Research Directory

A Phase 2 Study of Zanidatamab in Patients With HER2-expressing Tumors

The purpose of this study is to evaluate the efficacy and safety of zanidatamab for the treatment of participants with previously treated solid tumors that have Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry (IHC) 3+ overexpression.

An Open Label Phase 2 Study to Evaluate the Safety and Efficacy of Lenvatinib With Pembrolizumab or Lenvatinib, Pembrolizumab and FLOT in the Neoadjuvant / Adjuvant Treatment for Patients With Gastric Cancer

This study is an open label phase 2 study to evaluate the safety and efficacy of Lenvatinib with Pembrolizumab or Lenvatinib, Pembrolizumab and FLOT in the neoadjuvant / adjuvant treatment for Patients with Gastric Cancer.

Safety, PK and Efficacy of AI-061 in Advanced Solid Tumors

AI-061 is a co-formulation drug product (DP) consisting of 1:1 ratio mix of AI-025, an anti-PD-1 antibody, and ONC-392, an anti-CTLA-4 antibody. This is a dose escalation study to identify the maximum toxicity dose (MTD) or the recommended phase 2 dose (RP2D).

Dose Determining Study of EXS74539 (REC-4539) in Participants With Select Solid Tumors

The primary purpose of this study is to determine the safety, tolerability, and maximum tolerated dose (MTD) of EXS74539 (REC-4539) in participants with select solid tumors.

Dynamic Circulating Tumor DNA Monitoring to Guide Systemic Therapy in Gastric Cancer

This study aims to evaluate the clinical value of circulating tumor DNA (ctDNA) as a minimally invasive biomarker for monitoring treatment response and guiding systemic therapy in patients with gastric or gastroesophageal junction adenocarcinoma. Gastric cancer is often diagnosed at an advanced stage and shows substantial biological heterogeneity. Current treatment decisions mainly rely on imaging and clinical assessment, which may not reflect early molecular changes or minimal residual disease. Circulating tumor DNA, released from tumor cells into the bloodstream, can provide real-time information on tumor burden and treatment response through simple blood sampling. This is a prospective, open-label, phase II exploratory study conducted at a single center. Patients will be enrolled into three clinical cohorts according to their treatment stage: (1) neoadjuvant or conversion therapy cohort, (2) adjuvant therapy cohort after curative surgery, and (3) advanced or metastatic disease cohort receiving systemic therapy. Blood samples for ctDNA analysis will be collected before treatment and at predefined time points during treatment. The study will assess whether changes in ctDNA levels, including ctDNA clearance or reduction, are associated with treatment response, recurrence risk, and survival outcomes. In selected validation phases, treatment strategies may be adjusted based on ctDNA results, while all treatments remain within standard guideline-recommended regimens. The results of this study may help determine whether ctDNA can be used as a practical tool to improve treatment monitoring and support more personalized management of gastric cancer.

Combination of Immune Checkpoint in Locally Advanced or Metastatic MSI/dMMR Esogastric Adenocarcinomas

CIME is a multicenter, randomised, comparative, open-label phase III study aiming to compare the survival of patients suffering from MSI-H/dMMR locally advanced or metastatic oeasogastric adenocarcinoma treated by a bi-immunotherapy (experimental arm) versus standard current treatment (FOLFOX/XELOX + nivolumab : standard arm).

A Study Comparing BL-M05D1 With the Investigator's Choice of Treatment Regimen in Patients With Claudin (CLDN)18.2-Positive Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma (GC/GEJC) Who Have Received Prior First-Line Treatment

This trial is a registrational Phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-M05D1 in patients with Claudin (CLDN) 18.2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJC) who have received prior first-line treatment.

Surgery in Gastrointestinal Stromal Tumors (GISTs) for Treatment, Tumor Modeling, and Genomic Analysis

Objective: To follow people with GISTs and collect tumor tissue so that it can be studied in the lab. Eligibility: People age 6 and older who have a GIST. Design: Participants will be screened with a review of their medical records and samples. Participants will enroll in 1 other NIH study, and may be asked to enroll in 2 other optional NIH studies. Participants will have a medical history and physical exam. Data about how they function in their daily activities will be obtained. Participants may speak with a genetic counselor. They may have genetic testing. Participants will give blood samples. They may have a cheek swab. For this, small brush will be rubbed against the inside of the cheek. Participants may have a computed tomography (CT) scan of the chest, abdomen, and pelvis. Or they may have a CT scan of the chest and magnetic resonance imaging (MRI) of the abdomen and pelvis. Participants will be monitored every 6-12 months at the NIH Clinical Center, for up to 10 years before having surgery. If they need surgery, it will be performed at the NIH. Then, they will be monitored every 6-12 months, for up to 5 years after surgery. If a participant has surgery, tumor tissue samples and research specimen will be taken. If a participant does not need surgery, their participation will end after 10 years. If they have surgery, the 5-year monitoring period will restart after each surgery.

Magnetic Sentinel Lymph Node Mapping in Upper Gastro-Intestinal Cancer: A Feasibility Clinical Investigation

This is a multi-centre, partially blinded, side-by-side comparator study to assess the safety and tolerability, feasibility, and potential added diagnostic and clinical value of using the FerroTrace® and FerroMag Sentinel Lymph Node Mapping (SLNM) System for mapping sentinel lymph nodes (SLNs) in subjects with gastric, gastric-oesophageal junction, and oesophageal cancers, consisting of a safety lead-in phase and an expansion phase.

18F-FAPI PET/CT and MRI in Gastric Cancer

The purpose of this study was to evaluate the diagnostic efficacy and prognostic value of 18F-FAPI PET/CT combined with multiparameter MRI in gastric cancer.

Beta-Blockers on the Efficacy of Neoadjuvant Immunotherapy for Gastric Cancer

Study Population:Patients with locally advanced gastric cancer complicated by hypertension, who are scheduled to undergo laparoscopic gastric cancer resection after receiving preoperative immunotherapy. Primary Objective: To investigate the impact of combined beta-blocker use on the efficacy of immunotherapy in patients with locally advanced gastric cancer. Secondary Objective: To investigate the impact of combined beta-blocker use on the incidence of immune-related adverse events. Study Groups:This study does not include a parallel control group; it enrolls only a single study group. Study Design:This is a single-arm, exploratory clinical study. Study Duration:2026 - 2029 Sample Size: Single-arm, exploratory trial, planned enrollment of 33 cases. Inclusion Criteria: * Voluntarily sign the informed consent form; * Aged 18-75 years; * ECOG performance status 0-1; * Either sex; * Patients with a standardized histopathological diagnosis of gastric adenocarcinoma from the primary gastric lesion via endoscopic biopsy, according to the 15th edition of the Japanese Classification of Gastric Carcinoma (2017); * Patients judged by the treating physician to require preoperative immune checkpoint inhibitor therapy, followed by potentially curative gastrectomy; * Meet the diagnostic criteria for hypertension according to the 2023 Chinese Guidelines for the Management of Hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, or a previous diagnosis of uncontrolled hypertension), with an indication for beta-blocker use; * Deemed by a specialist to have no contraindications for beta-blocker use and can use beta-blockers for antihypertensive therapy. Exclusion Criteria * HER2-positive or microsatellite instability-high (MSI-H)/dMMR gastric cancer confirmed by immunohistochemistry; * Active autoimmune disease requiring continuous immunosuppressive therapy or history of transplantation; * Currently receiving systemic immunosuppressive medication: If a patient is currently using corticosteroids, the corticosteroid dose must be ≤ equivalent of prednisone 10 mg daily; * History of (non-infectious) pneumonitis/interstitial lung disease requiring treatment; * Concurrent infection with human immunodeficiency virus (HIV); * Pregnant or breastfeeding women; * History of psychiatric disorders; * Concurrent other malignancies or severe organ dysfunction; * Presence of contraindications for beta-blocker use (e.g., severe bradycardia, uncontrolled depression, unstable angina, uncontrolled heart failure (Class III or IV), hypotension (systolic blood pressure \<100 mmHg), severe asthma or chronic obstructive pulmonary disease (COPD), symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma, etc.); * Refractory hypertension; * Judged by the investigator as not meeting the inclusion criteria for this study. Effectiveness Analysis Primary Endpoint: Proportion of patients with Tumor Regression Grade (TRG) \< 3 (AJCC criteria). Secondary Endpoints: 3-year overall survival (OS), 3-year progression-free survival (PFS); correlation with immunotherapy-related biomarkers (e.g., PD-L1 expression, cortisol, adrenocorticotropic hormone, tumor tissue ADRB1 expression, tumor tissue RNA sequencing, tumor immune microenvironment); treatment compliance (immunotherapy completion rate, surgery delay rate). Safety Analysis:Incidence and severity of adverse events. Statistical Analysis:This is an exploratory, single-arm, uncontrolled study. The pathological response rate is the primary evaluation indicator, with a planned enrollment of 33 cases. The sample size was calculated based on the single-sample rate estimation method. Referring to similar exploratory immunotherapy combination studies and considering clinical practice, the anticipated pathological response rate is 80%. Using a two-sided α=0.05 (95% confidence level) and the Clopper-Pearson exact method, the two-sided 95% confidence interval for 33 samples is \[0.625, 0.918\], with an interval width of 0.294, which meets the core objective of preliminarily verifying the efficacy trend of the "standard immunotherapy + beta-blocker" regimen. A 10% dropout rate is also accounted for, balancing recruitment feasibility with basic statistical estimation precision. Descriptive statistical analysis will be used to calculate point estimates and 95% confidence intervals for primary and secondary endpoints. Survival analysis will use the Kaplan-Meier method to plot 3-year OS and PFS curves. Follow-up:Follow-up will be conducted at 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, and 36 months post-surgery.

A Study of Zolbetuximab (IMAB362) in Adults With Gastric Cancer

Zolbetuximab is being studied as a treatment for people with cancer in and around the stomach or cancer where the food pipe (esophagus) joins the stomach (gastroesophageal junction cancer). Most people with this type of cancer have a protein called Claudin 18.2 in their tumor. Zolbetuximab is thought to work by attaching to Claudin 18.2 in their tumor. This switches on the body's immune system to attack the tumor. There is an unmet medical need to treat people with advanced cancer in and around the stomach or gastroesophageal junction cancer. This study will provide more information on zolbetuximab given by itself and in combination with other treatments in adults with advanced stomach or gastroesophageal junction cancer. The study is currently ongoing globally. People in this study will either be treated with zolbetuximab by itself, with zolbetuximab and chemotherapy, with zolbetuximab and a medicine called pembrolizumab, or zolbetuximab with chemotherapy and a medicine called nivolumab. This study is ongoing, but enrollment in any of the treatment options has been completed. In addition, at this stage of the study, treatment in some of these treatment options has completed. The main aim of this study is to check how well zolbetuximab controls tumors when given by itself. Adults with cancer in and around the stomach or gastroesophageal junction cancer can take part. Their cancer is locally advanced unresectable or metastatic and has the CLDN18.2 marker in a tumor sample. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. They may have been previously treated with standard therapies. People cannot take part if they need to take medicines to suppress their immune system, have blockages or bleeding in their gut, have specific uncontrollable cancers such as symptomatic or untreated cancers in the nervous system, have a specific heart condition or infections. There are different treatments in the study. People who take part will receive just 1 of the treatments. Treatment will be given in cycles. The treatment is given through a vein; this is called an infusion. Some people with advanced disease will have 1 infusion in 3 week (21-day) cycles. Some people will have several infusions in 6 week (42-day) cycles. Some people with cancer in and around the stomach or gastroesophageal junction who have surgery for their cancer will have a few infusions in 2-week (14-day) cycles. This will happen before and after they have surgery for their cancer. People may receive chemotherapy for up to 6 months. Some people enrolled to received zolbetuximab and pembrolizumab, may have received pembrolizumab for up to 2 years. People will visit the clinic on certain days during their treatment; there may be extra visits during the first cycle of treatment. The study doctors will check if people had any medical problems from zolbetuximab and the other study treatments. Also, people in the study will have a health check including blood tests. On some visits they will also have scans to check for any changes in their cancer. Tumor samples will be taken at certain visits with the option of giving a tumor sample after treatment has finished. People will visit the clinic after they stop treatment. They will be asked about any medical problems and will have a health check including blood tests. After the clinic visits end some people will have a telephone health check every 3 months. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their treatment or not.

Dynamic ctDNA-Guided Adjuvant Therapy in cStage III and IVA Gastric or Gastroesophageal Junction Adenocarcinoma

This is a single-center, prospective, exploratory study evaluating the use of dynamic circulating tumor DNA (ctDNA) monitoring in the postoperative adjuvant treatment setting for patients with stage III or stage IVA gastric or gastroesophageal junction adenocarcinoma. After curative-intent surgery, patients remain at risk of disease recurrence. Postoperative treatment decisions are currently based on clinicopathological factors, which may not fully reflect minimal residual disease. ctDNA is a blood-based biomarker that can detect tumor-derived DNA fragments and may provide additional information on recurrence risk. In this study, ctDNA will be assessed at predefined perioperative and postoperative time points using peripheral blood samples. The primary objective is to evaluate 1-year disease-free survival. Secondary objectives include survival outcomes, safety, and longitudinal changes in ctDNA status. The findings of this exploratory study may inform future research on ctDNA-guided postoperative management in gastric cancer.

Study of Anti-CEACAM5 ADC M9140 in Participants With Advanced Solid Tumors (PROCEADE PanTumor)

The PROCEADE PanTumor study aims to investigate M9140 in multiple tumor types which express carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and it is therefore designed as a matrix study. This study aims to assess the antitumor activity, tolerability, safety, and pharmacokinetics (PK) of M9140 as monotherapy or in combination treatments in adult participants with locally advanced/metastatic CEACAM5 expressing tumors. There will be 3 substudies under this Master Protocol that may be conducted in parallel. * PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open-Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants with Advanced Gastric Cancer (Substudy GC); * PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open-Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants with Advanced Non-Small Cell Lung Cancer (Substudy NSCLC); * PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants With Advanced Pancreatic Cancer (Substudy PDAC).

A Phase 1, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours

This is a first-in-human, Phase 1, non-randomized, multicenter, open-label clinical study designed to investigate the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics (PK) of \[225Ac\]-FPI-2068, \[111In\]-FPI-2107, and FPI-2053 in metastatic and/or recurrent solid tumors (HNSCC, NSCLC, mCRC, PDAC, GC, RCC).

Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers

The primary purpose of this study is to assess the safety and tolerability of AB598 in participants with advanced malignancies.

Proximal Gastrectomy Anterior Anastomosis With Pyloroplasty Versus Esophagogastric Anastomosis for Gastric Cancer

This research is designed to compare proximal gastrectomy anterior anastomosis with pyloroplasty with esophagogastric anastomosis for gastric cancer. Gastroesophageal reflux disease, postoperative quality of life, short term outcomes, and long term outcomes will be compared.

Stapler Reinforcement Patches Compared to Standard Staplers in Gastrojejunostomy

This is a multi-center, prospective, randomized controlled study aimed at compareing the impact of stapler reinforcement patches versus standard staplers on postoperative complications in gastrojejunostomy.

Total Neoadjuvant Therapy With Short Course Radiation Therapy in Gastric Cancer

Standard treatment for patients with early stage gastric cancer consists of perioperative chemotherapy and surgical resection. If radiation therapy is administered in the adjuvant setting, the radiated area is often large and associated with significant toxicity. In this study, the investigators propose the addition of short course radiation therapy (SCRT) to chemotherapy in the neoadjuvant setting. The investigators hypothesize that this regimen of Total Neoadjuvant Therapy (TNT) will result in a higher rate of complete response (both pathologic and clinical), with less toxicity.

BAL0891 in Patients With Advanced Solid Tumors or Relapsed or Refractory Acute Myeloid Leukemia

This study is a multiple cohort, multicenter, open-label Phase 1 study with dose-escalation substudies investigating intravenous (IV) BAL0891 as monotherapy, and in combination with tislelizumab or paclitaxel, to determine the safety and tolerability of increasing doses of BAL0891 in patients with advanced solid tumors or relapsed or refractory acute myeloid leukemia. An adaptive model-based design will be used to guide the dose escalation. Subject assignment to Substudy 1, 2, 3 and 4 will be finalized following approval from the investigator and sponsor. The dose-expansion stage will be conducted with the RP2D to further evaluate the preliminary anti-tumor activity, safety, and tolerability in metastatic TNBC and GC.

A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies

This is a two-part, open-label, multicenter, dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and anti- tumor activity of ETX-19477, a novel reversible small molecule inhibitor of PARG.

18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) PET Imaging for Cancer Detection

Background: Fibroblast-activation protein (FAP) is an enzyme that appears in high numbers in cancer-associated fibroblasts of certain cancer types. \[18F\]FAPI-74 is a new PET (positron emission tomography) tracer, a substance that is injected into a person s body before an imaging scan. Researchers believe that \[18F\]FAPI-74 PET imaging may be able to visualize cancer more effectively than the approved tracers. If so, the new tracer would make it easier to find FAP-positive tumors in the body. Objective: To see if \[18F\]FAPI-74 PET scan is as good or better than other imaging methods for detecting certain cancers. Eligibility: People aged 18 years or older with one of these cancer types: pancreatic ductal adenocarcinoma (PDAC), cholangiocarcinoma, hepatocellular carcinoma (HCC), gastric cancer, bladder cancer, ovarian cancer, pheochromocytoma/paraganglioma (PPGL), small cell lung cancer (SCLC) or extrapulmonary neuroendocrine cancer (EP-NEC), mesothelioma or sarcoma. Participants must be scheduled or intended to receive treatment for cancer. Design: Participants will have 2 baseline scans: an \[18F\]FAPI-74, and the approved tracer \[18F\]-FDG. The \[18F\]FAPI-74 will be infused through a needle inserted into a vein. About 1 hour later, the participant will undergo imaging. Within 1 week, participants will undergo the same scanning procedures with the approved tracer. If the baseline scan with \[18F\]FAPI-74 shows the tumor(s), scans with this tracer will be repeated when their regular treatment regimen calls for scans again. If the scan with the regular FDG also show tumors, this scan will be repeated within the same week as the repeated \[18F\]FAPI-74 scan. If \[18F\]-FAPi PET scan shows no tumor(s), scans will not be repeated. If the participant's cancer progresses within 2 years, scans may be repeated. Follow-up calls will continue for 2 years.

Study of the Epidemiological, Clinical, Diagnostic, and Therapeutic Characteristics of Gastric Cancers in Algeria

The goal of this observational study is to describe the demographic, epidemiological, clinical, and outcome characteristics of patients with gastric cancer. It also aims to analyze the diagnostic approaches and management strategies used in the care of these patients in Algeria.

[18F]FPyQCP PET Imaging of Fibroblast Activation Protein in Selected Oncology Indications

This is a multi-center, open-label, single-arm, Phase 1/2 study designed to evaluate the safety, radiation dosimetry, and preliminary diagnostic performance of \[18F\]FPyQCP in detecting colorectal cancer (CRC), gastric cancer (GC), pancreatic ductal adenocarcinoma (PDAC), invasive lobular breast cancer (ILC), and epithelial ovarian cancer (EOC).