A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib)

Exclusion Criteria

• •Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy, or increasing doses of corticosteroids within the prior 2 weeks.
• •History of severe hypersensitivity reactions to other monoclonal antibodies.
• •Out of range laboratory values for measures of hepatic and renal function, electrolytes and blood counts
• •Impaired cardiac function or clinically significant cardiac disease.
• •Patients with active, known or suspected autoimmune disease.
• •Human Immunodeficiency Virus infection at screening.
• •Escalation part: Active Hepatitis B (HBV) or Hepatitis C (HCV) virus infection at screening.
• •Expansion part: Patients with active HBV or HCV are excluded, excepting those patients undergoing treatment for HBV or HCV.
• •Malignant disease, other than that being treated in this study.
• •Recent systemic anti-cancer therapy
• •Active infection requiring systemic antibiotic therapy.
• •Patients requiring chronic treatment with systemic steroid therapy, other than replacement dose steroids in the setting of adrenal insufficiency or treatment with low, stable dose of steroid (\<10mg/ day prednisone or equivalent) for stable CNS metastatic disease.
• •Patients receiving systemic treatment with any immunosuppressive medication, excepting the above
• •Use of any live vaccines against infectious diseases (e.g. influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment.
• •Participation in an interventional, investigational study within 2 weeks of the first dose of study treatment.
• •Presence of ≥ CTCAE grade 2 toxicity (except alopecia and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer therapy.
• •Recent use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, M-CSF)
• •Patients with tuberculosis (TB). Note: Patient with latent TB may be eligible based on the investigator's benefit-risk assessment.
• •Patients who have been infected with HBV or HCV including those with inactive disease.
• •Patients with TB. Note: Patient with latent TB may be eligible based on the investigator's benefit-risk assessment.
• •Patients with history of and/or active inflammatory bowel disease.
• •Active skin or soft tissue infection including cellulitis, erysipelas, impetigo, furuncle,carbuncle, abscess, or fasciitis.
• •Active candida infection, including mucocutaneous infection or history of invasive candidiasis.
• •Patients with history of retinal vein oclusion.
• •Patients with history of interstitial lung disease or pneumonitis.
• •Patients with cardiomyopathy and/or LVEF \< LLN.
• •Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral combination partners.
• •Hemoglobin (Hgb) \< 9 g/dL without growth factor or transfusion support
• •Women of child-bearing potential using hormonal contraception, unless an additional contraception method is also used according to the Mekinist® label.
• •NSCLC patients with EGFR mutant tumors.
• •Strong inhibitors and strong inducers of CYP3A4 should not be used concomitantly.
• •Patients with history of interstitial lung disease.
• •Patients who have been infected with HBV or HCV including those with inactive disease.
• •Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral combination partners
• •Patients cannot have received radiotherapy to lung fields within 6 months of study treatment start.