Oesophageal cancer metastatic Trials in Disease

Study of HLX22, Trastuzumab, and Chemotherapy for Patients with Advanced or Metastatic Stomach and Gastroesophageal Cancer

This trial is investigating a new treatment combination for patients with locally advanced or metastatic cancer of the gastroesophageal junction and stomach. The study focuses on patients whose cancer has spread to nearby areas or to other parts of the body and cannot be removed by surgery.

Main inclusion criteria: To participate, you must be at least 18 years old and have a confirmed diagnosis of previously untreated, locally advanced or metastatic gastroesophageal junction or gastric cancer that is HER2-positive. HER2-positive means your tumor has higher levels of a specific protein called HER2, which can be targeted by certain treatments. You must have measurable disease that can be assessed by imaging scans, and it should not be only in the bones. Your organs must be functioning adequately, and you need an ECOG performance status of 0-1, meaning you are able to carry out most daily activities with little or no difficulty. You must be expected to live for at least 6 months. Women of childbearing potential must have a negative pregnancy test, and both men and women must agree to use effective birth control during the study and for at least nine months after the final treatment dose. You must also test negative for HIV, Hepatitis B, and Hepatitis C, or meet specific conditions if you test positive.

Main exclusion criteria: You cannot participate if you have other types of cancer unrelated to the study, if you have received certain prior cancer treatments, or if you have serious heart conditions or other severe health problems. Pregnant or breastfeeding women are not eligible. Patients who are unable to follow study procedures or attend required visits, those with known allergies to the study medications, or those participating in another clinical trial at the same time may also be excluded.

Focus and goal: The trial aims to evaluate whether a new combination treatment involving HLX22, trastuzumab, and chemotherapy (XELOX) works better than the standard treatment of trastuzumab and chemotherapy with or without pembrolizumab as a first-line therapy. The study is designed as a double-blind trial, meaning neither you nor the researchers will know which treatment you are receiving to ensure unbiased results. Key outcomes include measuring how long patients live without their cancer getting worse (progression-free survival) and overall survival. The study will also monitor the safety of the treatments and any side effects that occur.

Investigational drugs: HLX22 is a monoclonal antibody that targets the HER2 protein on cancer cells, helping the immune system recognize and attack them. Trastuzumab is another monoclonal antibody that also targets HER2, blocking signals that tell cancer cells to grow and divide. Pembrolizumab is an immune checkpoint inhibitor that helps the immune system fight cancer by blocking proteins that prevent it from working properly. XELOX is a chemotherapy combination consisting of capecitabine (taken by mouth) and oxaliplatin (given through a vein), which work together to kill fast-growing cancer cells by damaging their DNA and stopping their growth.

Study of Trastuzumab Deruxtecan and Drug Combination for Patients with Advanced or Metastatic HER2-Positive Gastric or Gastroesophageal Junction Cancer

This trial is exploring new treatment options for patients with HER2-positive cancer affecting the stomach or the area where the stomach meets the esophagus. The study is testing whether combining Trastuzumab Deruxtecan (also known as Enhertu) with chemotherapy, with or without the immunotherapy drug Pembrolizumab, is more effective than the current standard treatment.

Main inclusion criteria: You must be at least 18 years old and have HER2-positive gastric or gastroesophageal junction cancer that is advanced or has spread to other parts of the body and cannot be removed by surgery. You should not have received prior treatment for your advanced cancer. Your cancer must have at least one tumor that can be measured on a CT or MRI scan. A tumor sample must be tested to confirm HER2-positive status and PD-L1 expression, which is a protein that affects immune system response. You must have adequate organ and bone marrow function, a left ventricular ejection fraction (a measure of how well your heart pumps blood) of at least 50%, and an ECOG performance status of 0 or 1, meaning you are fully active or have some symptoms but do not require bed rest during the day. If you can have children, you must agree to use highly effective birth control during the trial and for a specified time afterward. You must be willing to attend scheduled visits, follow the trial plan, and participate in questionnaires about your health and well-being.

Main exclusion criteria: You cannot participate if you have other types of cancer unrelated to this study, if you have had another cancer treatment within a certain period before the study, or if you have serious heart problems or uncontrolled high blood pressure. Active infections requiring treatment, pregnancy, breastfeeding, allergies to the study medications, a history of severe allergic reactions, or a history of drug or alcohol abuse will exclude you from participation. Patients unable to follow study procedures are also not eligible.

Focus and goal: The trial aims to determine whether the new treatment combination of Trastuzumab Deruxtecan with chemotherapy, with or without Pembrolizumab, is more effective than the standard treatment of chemotherapy and Trastuzumab, with or without Pembrolizumab. Participants will receive treatment through intravenous injection over a period of up to 60 weeks. The study will monitor cancer progression through regular imaging tests such as MRI or CT scans and assess any side effects. The goal is to provide valuable information on whether this new combination could lead to improved outcomes for patients with this type of cancer.

Investigational drugs: Trastuzumab Deruxtecan (Enhertu) is an antibody-drug conjugate that combines a targeted therapy with chemotherapy. It targets the HER2 protein on cancer cells and delivers a chemotherapy agent directly to these cells to help destroy them. Pembrolizumab is an immunotherapy medication that works by helping your immune system recognize and attack cancer cells. Trastuzumab is a monoclonal antibody that attaches to the HER2 protein on cancer cells, helping to slow down or stop their growth. These medications are administered through intravenous infusion directly into the bloodstream.

Summary

Both ongoing clinical trials focus specifically on HER2-positive cancer affecting the gastroesophageal junction and stomach, highlighting the importance of HER2 status in treatment selection. The trials are widely distributed across Europe, with the second trial available in 12 countries compared to 7 countries for the first trial, offering broader geographic access to patients.

A notable commonality is that both studies are investigating combinations of HER2-targeted therapies with chemotherapy, and both include options for adding the immunotherapy drug Pembrolizumab. The first trial tests HLX22, a newer monoclonal antibody, while the second evaluates Trastuzumab Deruxtecan (Enhertu), an antibody-drug conjugate. Both trials require patients to have previously untreated advanced disease and adequate organ function, with similar performance status requirements.

These trials represent important research efforts to improve first-line treatment options for patients with HER2-positive metastatic disease affecting the gastroesophageal junction, with a focus on combining different mechanisms of action to enhance treatment effectiveness.