This is a randomized phase 2 trial aiming to assess the early efficacy of two experimental treatment sequences. Three arms are planned; (i) standard chemotherapy followed at progression by single agent immunotherapy with durvalumab (CT), (ii) experimental single agent immunotherapy with durvalumab followed at progression by chemotherapy, (iii) experimental combination immunotherapy with durvalumab+tremelimumab followed at progression by chemotherapy. The the two experimental strategies will be compared with the standard strategy in terms of 12-month overall survival, time considered informative for the type of treatment and disease
Name: Chemotherapy
Description: Any approved first line chemotherapy regimen at Investigators' choiceType: DrugChemo first Immuno Monotherapy first Immuno Combination Therapy first
Name: Durvalumab
Description: Durvalumab 1500 mg iv Q4w until progressive or unacceptable toxicity or patient's refusalType: DrugChemo first Immuno Monotherapy first Immuno Combination Therapy first
Name: Tremelimumab
Description: Tremelimumab 75 mg iv Q4w for 4 administrations (4 months)Type: DrugImmuno Combination Therapy first
Description: 12-month overall survival is defined as the Kaplan-Meier (K-M) survival probability at 12 months after randomization (Chen 2015).
Measure: 12-month overall survival Time: 12 monthsAllocation: Randomized
Parallel Assignment
There is one SNP
Exclusion Criteria: Cancer related 1. Activating epidermal growth factor receptor mutation (exon19 deletion or exon 21 L858R mutation or other activating/sensitizing mutations). --- L858R ---