A phase 1/2 multiple-indication biomarker, safety, and efficacy study in advanced or metastatic Gastrointestinal cancers exploring treatment comBinations with peLarEorep and aTezolizumab (GOBLET)

You likely can't join if

• C1-C4: 1. Undergone systemic chemotherapy, radiotherapy, or surgery, <4 weeks before study treatment 2. Received previous treatment with immune checkpoint inhibitors 3. Uncontrolled hypertension (systolic blood pressure ≥150 mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with hypotensive agents 4. Acute coronary syndrome (including myocardial infarction and unstable angina), and/or a history of coronary angioplasty or stent placement performed within 6 months of enrollment 5. A large amount of pleural effusion or ascites requiring more than weekly drainage 6. A history of (non-infectious) pneumonitis that required steroids or currently active pneumonitis 7. A ≥grade 3 active infection according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. 8. Symptomatic brain metastasis. (Patients with asymptomatic and stable brain metastasis are eligible for study enrollment.) 9. Interstitial lung disease with symptoms or signs of activity 10. In C1, C2, and C3 only: Positive test results for either anti-human immunodeficiency virus (HIV)-1 antibodies, anti-HIV-2 antibodies, antihuman T cell leukemia virus type 1 (HTLV-1) antibodies, hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (HCV) antibodies.* Testing is not required unless deemed necessary by the investigator * Patients who test positive for anti-HBc antibodies or have detectable HBV-DNA will also be excluded In C4 only: Positive test results for either anti-HIV-1 or HIV-2 antibodies if the CD4+ T cell is <300 cells/μl.* Testing for HIV status is required * To be eligible, HIV+ patients must have an undetectable viral load and be receiving highly active antiretroviral therapy (HAART). Patients must be on established HAART therapy for at least 4 weeks prior to study entry 11. Autoimmune disease that has required systemic treatment in the past 2 years with disease modifying agents, corticosteroids, or immunosuppressive drugs. [Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment] 12. A history or findings of ≥grade 3 congestive heart failure according to the New York Heart Association functional classification. 13. A seizure disorder that requires pharmacotherapy 14. Proteinuria ≥grade 3 (using spot testing; if grade 3, repeat with midstream urine; if still grade 3, then urine collection for 24 hours to confirm grade) as per NCI CTCAE 15. A medical contraindication to undergoing biopsies 16. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation 17. A non-healing wound, non-healing ulcer, or non-healing bone fracture within 4 weeks prior to the start of study drug. 18. Women who are pregnant or breastfeeding 19. A diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing >10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug 20. Any vaccine during screening and the first cycle of treatment 21. Legal incapacity or limited legal capacity
• C5: 1. Previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic PDAC. Palliative radiotherapy for pain control of metastatic bone lesions is allowed 2. Received previous treatment with immune checkpoint inhibitors 3. History of allergy or known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation, and/or contraindication to any of the study treatments (as outlined in local prescribing information) 4. Known low or absent dihydropyrimidine dehydrogenase (DPD) activity 5. Uncontrolled or severe cardiac disease (history of unstable angina, myocardial infarction, coronary stenting, or bypass surgery within the prior 6 months), symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation) 6. Women currently pregnant or breastfeeding 7. Active, uncontrolled infections 8. Symptomatic brain metastasis 9. Known leptomeningeal disease. 10. History of interstitial lung disease 11. Known active HIV, Hepatitis B (HBV) or Hepatitis C (HCV) infection 12. Active, known, or suspected autoimmune disease 13. Receiving immunosuppressive or myelosuppressive medications that would increase the risk of serious neutropenic complications 14. Seizure disorder that requires pharmacotherapy 15. A non-healing wound, non-healing ulcer, or non-healing bone fracture within 4 weeks prior to the start of study drug 16. Any vaccine within 28 days prior to first study treatment or during the first cycle of treatment 17. History of another primary cancer within the last 3 years