German Clinical Trials Register

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1. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study prior to inclusion and during the study. 2. Medical or psychological conditions that would jeopardize an adequate and orderly completion of the trial. 3. Prior immunotherapy or use of other investigational agents, including prior treatment with an anti- Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T-lymphocyte associated antigen4 (anti-CTLA-4) antibody, therapeutic cancer vaccines. 4. Any other concurrent antineoplastic treatment including chemotherapy, biologic or hormonal therapy or irradiation - Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to study entry. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable. 5. Any unresolved toxicity NCI CTCAE (V5.0) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria - Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the medical monitor. - Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the medical monitor. 6. Major surgical procedures, open biopsy or significant traumatic injury within 4 weeks prior to treatment start (minor procedures within 1 week) 7. Prior radiation therapy within 14 days prior to study entry. 8. History of allogenic organ transplantation. 9. History of autologous/allogenic bone marrow transplant. 10. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion: a) Patients with vitiligo or alopecia b) Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement c) Any chronic skin condition that does not require systemic therapy d) Patients without active disease in the last 5 years may be included but only after consultation with the study physician e) Patients with celiac disease controlled by diet alone 11. Uncontrolled intercurrent illness, including but not limited to, symptomatic congestive heart failure (New York Heart Association Class III or IV), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, compromise the ability of the patient to give written informed consent or could compromise protocol objectives in the opinion of the Investigator and/or Sponsor. 12. Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrolment. History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") within 3 months of enrolment. 13. Have Fridericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or history of congenital long QT syndrome. Any ECG abnormality that in the opinion of the Investigator would preclude safe participation in the study; patients with pacemakers where QTc is not a reliable measure will require an evaluation by a cardiologist to exclude co-existing cardiac conditions which would prohibit safe participation in the study. 14. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or ascites. 15. History of another primary malignancy except for a) Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IMP and of low potential risk for recurrence b) Adequately treated non-melanoma skin cancer (basal cell, squamous cell carcinoma) or lentigo maligna without evidence of disease c) Adequately treated carcinoma in situ of the cervix or breast without evidence of disease 16. History of leptomeningeal carcinomatosis 17. History of active primary immunodeficiency 18. Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy. 19. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen [HBsAg) result], hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 20. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion: a) Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) b) Systemic corticosteroids at physiologic doses not to exceed <10 mg/day of prednisone or its equivalent c) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 21. Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IMP and up to 30 days after the last dose of IMP. 22. Female patients who are pregnant or breastfeeding. 23. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 24. Distant metastases by CT or MRI of abdomen, pelvis, and thorax, bone scan or MRI (if bone metastases are suspected due to clinical signs). Infiltration of any adjacent organs or structures by CT or MRI, indicating an unresectable situation. 25. Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have a CT/ MRI of the brain prior to study entry. 26. Any co-existing medical condition that in the investigator’s judgement will substantially increase the risk associated with the patient’s participation in the study. 27. Preexisting hearing impairment