9. Adequate hepatic function: bilirubin ≤ 1.5 x ULN, AST/ALT ≤ 1.5 x ULN, AP ≤ 2.5 x ULN.
10. Adequate renal function: calculated creatinine clearance ≥ 60 mL/min, according to the formula of Cockcroft-Gault.
11. Women with child-bearing potential who are using effective contraception, are not pregnant or lactating and agree not to become pregnant during participation in the trial and during 90 days after the last treatment. A negative serum pregnancy test performed within 7 days before registration into the trial is required for all women with child-bearing potential. Men agree not to father a child during participation in the trial and during 90 days after the last treatment.
12. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up.
You may not be if
1. Presence of any distant metastasis or N2 or N3 disease.
2. Patients with a history of other malignancies, except non-active malignancy that does not require treatment, nor anticipated to require treatment for the duration of the study, and in the opinion of the investigator would not pose a risk of increased toxicity, or difficulty to follow the protocol and assess endpoints of the study.
3. Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab.
4. Absolute contraindications for the use of corticosteroids as premedication.
5. Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to registration.
6. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses (i.e., which must not exceed 10 mg/day of prednisone or an equivalent corticosteroid).
7. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure NYHA III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 3 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
8. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Bazett's Correction.
9. Body weight less than 30 kg.
10. Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: - Vitiligo or resolved childhood asthma/atopy - Hypothyroidism stable on hormone replacement or Sjorgen's syndrome
11. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
12. Known evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.
13. History of primary immunodeficiency.
14. History of allogeneic organ transplant.
15. Receipt of live attenuated vaccination within 30 days prior to the first dose of durvalumab (COVID-19 vaccine is permitted).
16. Any concomitant drugs contraindicated for use with durvalumab: this includes systemic corticosteroids, methotrexate, azathioprine, and tumor necrosis factor (TNF)-α blockers. Any concomitant drugs contraindicated for use with the other trial drugs according to the locally approved product information.
17. Any other serious underlying medical (e.g., uncontrolled diabetes mellitus, active uncontrolled infection, active gastric ulcer, uncontrolled seizures, severe hearing impairment), psychiatric, psychological, familial or geographical condition that, in the judgment of the investigator, may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.
