Perlmutter Cancer Center

Claudin 18.2 protein, or CLDN18.2 is a protein found on cells in the digestive system. It is also found on some tumors. Researchers are looking at ways to attack CLDN18.2 to help control tumors. ASP2138 is thought to bind to 2 targets at the same time: CLDN18.2 and a protein called CD3 found on immune cells, called T-cells. ASP2138 works by binding to both the tumor cell and CD3 which "tells" the immune system to attack the tumor. ASP2138 is a potential new treatment for people with stomach cancer, gastroesophageal junction cancer, (cancer where the tube that carries food (esophagus) joins the stomach) or pancreatic cancer. Before ASP2138 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. This information will help to find a suitable dose and to check for potential medical problems from the treatment. Adults 18 years or older with stomach cancer, gastroesophageal junction cancer, or pancreatic cancer can take part. Their cancer is locally advanced unresectable or metastatic. 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. The main aims of the study are to check the safety of ASP2138, how well it is tolerated, and to find a suitable dose of ASP2138 to be used later in this study. This is an open-label study. This means that people in this study and clinic staff will know that people will receive ASP2138. The study will have 2 phases. In phase 1, different small groups of people will receive lower to higher doses of ASP2138. Any medical problems will be recorded at each dose. This is done to find suitable doses of ASP2138 to use later in the study. The first group will receive the lowest dose of ASP2138. A medical expert panel will check the results from this group and decide if the next group can receive a higher dose of ASP2138. The panel will do this for each group until all groups have received ASP2138, or until suitable doses have been selected for later in the study. Doctors will also check how each type of cancer is responding to ASP2138. In phase 1b, other different small groups will receive suitable doses of ASP2138 found from phase 1. This phase will check how each type of cancer responds to ASP2138. The response to ASP2138 is measured using scans and blood tests. Doctors will continue to check all medical problems throughout the study. ASP2138 will be given through a vein in the arm. This is called an infusion. People will receive weekly infusions of ASP2138 in a 14-day (2-week) treatment cycle. People will continue to receive treatment until: their cancer gets worse; they have medical problems they can't tolerate; they ask to stop treatment; the doctors decide that continuing treatment is no longer in that person's best interest; the study is ended by the sponsor. Doctors will check if people had any medical problems from ASP2138. Other checks will include medical examinations, checking the nervous system, blood and urine tests and vital signs. Nervous system checks include checking peoples state of mind, reflexes, balance, movement and muscle strength. Vital signs include medical examinations, body temperature, breathing rate, and blood oxygen levels. Electrocardiograms (ECG) will be done to check the heart rhythm during the study. People will receive ASP2138 in a hospital. They will have blood tests and doctors will check for medical problems. People will also visit the clinic on certain days during their treatment, with extra visits during the first 3 cycles of treatment. People will visit the clinic after treatment has finished. The doctors will check for more medical problems. Other checks will include medical examinations, blood and urine tests, and vital signs. People will also have an ECG. After this, people will visit the clinic for a check-up several times. 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.