Study on Cabozantinib and Durvalumab, With or Without Tremelimumab, for Patients with Gastroesophageal and Other Gastrointestinal Cancers

Inclusion Criteria

• Be 18 years or older.
• Have a good overall health status, with an ECOG performance score of 0 or 1, meaning fully active or restricted in physically strenuous activity but ambulatory.
• Have a confirmed diagnosis of one of the following cancers:
  • Gastric or gastroesophageal junction adenocarcinoma
  • Esophageal adenocarcinoma
  • Colorectal adenocarcinoma (CRC)
  • Hepatocellular carcinoma (HCC)
• Have advanced (stage 4) or locally advanced (stage III) cancer that cannot be removed by surgery.
• Have measurable cancer according to standard criteria.
• Agree to undergo a biopsy procedure before starting the study and possibly during the study.
• For gastric, gastroesophageal, or esophageal cancer, have shown progression or intolerance to at least one previous standard treatment.
• For CRC, have shown progression or intolerance to at least two previous standard treatments, and if applicable, have failed treatment with specific antibodies.
• For HCC, be either treatment-naive or have shown progression or intolerance to at least one previous standard treatment.
• Have known results for specific tumor markers, or agree to have them tested.
• Have recovered from any side effects of previous treatments to a mild level or baseline.
• Weigh more than 66 pounds (30 kg).
• Have adequate organ and bone marrow function.
• For women, show evidence of post-menopausal status or have a negative pregnancy test if pre-menopausal.
• Agree to use effective contraception during the study and for 180 days after the last treatment.

Exclusion Criteria

• Have previously been treated with certain immune checkpoint inhibitors, except for specific cases in HCC and gastric/esophageal cancer.
• Have previously been treated with cabozantinib or similar drugs.
• Have had certain abdominal issues, like fistulas or perforations, within 6 months before starting the study.
• Have active or untreated ulcers, bowel diseases, or other specific gastrointestinal conditions.
• Be unable to swallow tablets.
• Have uncontrollable fluid buildup in the abdomen or around the lungs.
• Have certain lung conditions or significant bleeding issues.
• Have unresolved side effects from previous cancer treatments.
• Have had extensive radiation therapy recently.
• Have had major surgery recently.
• Be using immunosuppressive medications recently, with some exceptions.
• Have a history of organ transplantation.
• Have active or past autoimmune or inflammatory disorders.
• Have active infections, including tuberculosis, hepatitis B or C, or HIV, with some exceptions for HCC patients.
• Have received a live vaccine recently.
• Have uncontrolled high blood pressure.
• Have had recent serious cardiovascular events.
• Have untreated brain metastases or certain other serious conditions.
• Have a history of another primary cancer, with some exceptions for certain treated cancers.
• Be using certain blood thinners, with some exceptions for low-dose or specific types of anticoagulants.
• Have known allergies to any of the study drugs.