A Phase III Prospective Double Blind Placebo Controlled Randomized Study of Adjuvant MEDI4736 In Completely Resected Non-Small Cell Lung Cancer
A Phase III Prospective Double Blind Placebo Controlled Randomized Study of Adjuvant MEDI4736 In Completely Resected Non-Small Cell Lung Cancer
The purpose of this study is to find out whether it is better to receive a new drug, MEDI4736, or better to receive no further treatment after surgery (and possibly chemotherapy) for lung cancer.
Inclusion Criteria:
Histologically confirmed diagnosis of primary non-small cell carcinoma of the lung. according to WHO Classification of Tumours (WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. WHO/IARC Classification of Tumours, 4th Edition, Volume 7). Patients with large-cell neuroendocrine carcinomas are not eligible.
Patients must be classified post-operatively as Stage IB (ā„ 4cm in the longest diameter), II or IIIA on the basis of pathologic criteria. Note: Although T3N2M0 tumours have been reclassified to stage IIIB in the 8th edition of the IASLC staging system, these patients remain eligible (as stage IIIA under the 7th edition criteria).
Note: Patients with synchronous primary tumours will not be eligible due to the potential uncertainty regarding their appropriate PD-L1 status.
Prior Systemic Therapy:
Radiation:
ā¢ Patients with N2 disease only who receive adjuvant post-operative radiation therapy are eligible provided they meet the protocol specified timing criteria for surgery, adjuvant chemotherapy and randomization. Pre-operative radiation therapy is not permissible.
Total bilirubin* ā¤ institutional upper limit of normal Alkaline phosphatase ā¤ 2.5 x institutional upper limit of normal AST(SGOT) and ALT(SGPT) ā¤ 2.5 x institutional upper limit of normal Creatinine Clearance ā„ 40 ml/min
* excluding Gilbert's syndrome
Creatinine clearance to be measured directly by 24 hour urine sampling or as calculated by Cockcroft Formula:
Females: GFR = 1.04 x (140-age) x weight in kg serum creatinine in Ī¼mol/L Males: GFR = 1.23 x (140-age) x weight in kg serum creatinine in Ī¼mol/L
Exclusion Criteria:
Patients with a history of other malignancies, except:
A combination of small cell and non-small cell lung cancer, pulmonary carcinoid tumour or large-cell neuroendocrine carcinoma (LCNEC).
History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjƶgren's syndrome, Guillain-BarrƩ syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. NOTE: patients with Grave's disease and/or psoriasis not requiring systemic therapy within the last two years from randomization and patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement are not excluded.
History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization* or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy.
Live attenuated vaccination administered within 30 days prior to randomization.
History of hypersensitivity to MEDI4736 or any excipient.
Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if controlled, must have a LVEF > 50% within 12 weeks prior to randomization.
Concurrent treatment with other investigational drugs or anti-cancer therapy.
Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol. This includes but is not limited to:
Pregnant or lactating women. Women of childbearing potential must have a urine pregnancy test proven negative within 14 days prior to randomization. Men and women of child-bearing potential must agree to use adequate contraception.
Cachoeiro de Itapemirim, EspĆrito Santo 29308020, Brazil
Porto Alegre, Rio Grande do Sul 90110270, Brazil
Nishinomiya-shi, HyÅgo 663-8501, Japan
New Taipei City;, Taiwan 220, Taiwan
Vinnitsia, 21029, Ukraine