Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

To join this study, you need to be 18 years old or older and weigh more than 5.5 stone (35 kg). You must have stomach or GEJ cancer that hasn't been treated yet for its advanced stage, meaning it's either spread or can't be removed by surgery. Your cancer also needs to be 'measurable', which means doctors can clearly see and track its size.

You'll also need to be generally fit, with your daily activities not severely limited by your illness (doctors call this having an ECOG PS of zero or one), and expected to live at least another 12 weeks. Importantly, your body's organs, like your liver and kidneys, and your blood all need to be working well. Doctors will also check your cancer for something called Claudin18.2, either from old tissue samples or a new biopsy, as this study specifically looks at cancers with this feature.

There are also reasons why you might not be able to join. For example, if your cancer has a different feature called HER2-positive, or if you have certain problems like untreated brain tumours, uncontrolled fluid in your tummy, active infections like HIV or hepatitis, or certain autoimmune conditions. You also can't have had specific types of previous cancer treatments, especially those that target the same Claudin18.2 feature or certain immune-boosting drugs.

If you join this study, you will be part of one of four smaller groups, each testing a different combination of medicines. You will receive either Rilvegostomig, Volrustomig, AZD0901, or 5-Fluorouracil, Capecitabine, possibly combined with other drugs like FOLFOX or XELOX. These medicines will be given according to a set schedule, which your study team will explain fully.

Throughout the study, you will have regular visits to the clinic. These visits will involve various assessments, such as blood tests (to check how your body is handling the medicine and to look for specific markers), scans (to see how your cancer is responding), and physical examinations. You will also be asked about any side effects you might be experiencing. The exact number of visits and the full duration of your participation will depend on how you respond to the treatment and which group you are in, but the study will involve ongoing treatment and monitoring for a significant period. You will have regular checks, and your health will be carefully watched. The study team will provide all the information about how long you'll be involved and what each visit entails.