Safety And Efficacy Study Of Avelumab Plus Chemotherapy With Or Without Other Anti-Cancer Immunotherapy Agents In Patients With Advanced Malignancies

Exclusion Criteria

• •1. Prior immunotherapy with any antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
• •2. Patients with known symptomatic central nervous system metastases requiring steroids.
• •3. Diagnosis of other malignancy within 2 years prior to enrollment except adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the bladder, breast, or cervix, or low grade (Gleason ≤6) prostate cancer
• •4. Use of immunosuppressive medication at the time of enrollment
• •5. Active or prior autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent.
• •6. Prior organ transplantation including allogenic stem cell transplantation
• •7. Active infection requiring systemic therapy
• •8. Known history of HIV or AIDS
• •9. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening
• •10. Administration of live vaccine within 4 weeks prior to study entry
• •11. Known prior severe hypersensitivity to the investigational products or any component in their formulations,
• •12. Known prior severe hypersensitivity to platinum-related compounds for all cohorts, to pemetrexed for patients enrolled in Cohort A1 and Cohort A3, and to gemcitabine for patients enrolled in Cohort A2 and Cohort A4
• •13. Persisting toxicity related to prior therapy (NCI CTCAE v4.03 Grade \> 1)
• •14. Known history of colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis.
• •15. Ongoing cardiac dysrhythmias of NCI CTCAE v4.03 Grade 2 or prolongation of the QTcF interval to \>480 msec.
• •16. Clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure, or serious cardiac arrhythmia requiring medication.
• •17. Major surgery ≤28 days or major radiation therapy ≤14 days prior to enrollment.
• •18. Participation in other studies involving investigational drug(s) within 28 days prior to study entry.
• •19. Concurrent treatment with a prohibited medication.
• •20. Other acute or chronic medical or psychiatric condition
• •21. Pregnant female patients; breastfeeding female patients; fertile male patients and female patients of childbearing potential who are unwilling or unable to use at least 1 highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 90 days after the last dose of chemotherapy (for male and female patients) or at least 30 days after the last dose of avelumab (for female patients), whichever is longer.