NIVORAD - A randomised phase 2 trial of nivolumab and stereotactic ablative body radiotherapy in advanced non-small cell lung cancer, progressing after first or second line chemotherapy.

Exclusion Criteria16

• Active, known or suspected autoimmune disease. Patients are not excluded if they have vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to an autoimmune condition requiring only hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Any condition requiring systemic treatment with either regular corticosteroids (>10mg daily prednisone or equivalent dose of an alternative corticosteroid) or other immunosuppressive medications within 14 days of study drug administration. Intranasal, inhaled or topical steroids are permitted in the absence of active autoimmune disease.
• Patients with leptomeningeal or uncontrolled brain metastases are excluded. Controlled brain metastases are those which have been treated and are radiologically and/or clinically stable, and the patient is asymptomatic and does not require corticosteroids.
• Actionable mutation for which an approved, targeted therapeutic is available, e.g. known mutation of epidermal growth factor receptor (EGFR) or translocation of anaplastic lymphoma kinase.
• Chemotherapy in the last 4 weeks.
• Radiotherapy in the last 2 weeks.
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
• Current treatment with other investigational drugs or anti-cancer therapy.
• Life expectancy of less than 3 months.
• History of another malignancy within 3 years prior to randomisation. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 3 years after definitive primary treatment.
• Receipt of live attenuated vaccination within 30 days prior to registration.
• Positive test for hepatitis B virus surface antigen (HBVsAg) or antibodies to hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
• History of other significant infection, including HIV. HIV testing not mandatory unless clinically indicated.
• Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
• Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception to avoid pregnancy for 23 weeks after the last dose of nivolumab. Women of childbearing potential must have a negative pregnancy test done within 24 hours prior to randomisation. Men must have been surgically sterilised or use a (double if required) barrier method of contraception if they are sexually active with a woman of child bearing potential for a period of 31 weeks after the last dose of nivolumab.
• Recipients of a transplanted solid organ (kidney, liver, heart, lung) or of allogeneic bone marrow.