Levy BP, et al. - In this phase 2 trial including patients with advanced non-small cell lung cancer (NSCLC) with one prior line of platinum-containing therapy, researchers assessed the efficacy of second-line pembrolizumab + CC-486 (oral azacitidine). The participants received CC-486 or placebo, using randomization in a ratio of 1:1, on days 1–14, in combination with pembrolizumab on day 1 of a 21-day cycle. The study population comprised 100 patients randomised (pembrolizumab + CC-486: 51; pembrolizumab + placebo: 49). Most of these were male (57.0%), were white (87.0%) and had Eastern Cooperative Oncology Group performance status 1 (68.0%). The pembrolizumab + CC-486 and pembrolizumab + placebo arms were not significantly different in terms of progression-free survival (PFS) (median, 2.9 and 4.0 months, respectively). A shorter median treatment duration (15.0 vs 24.1 weeks), and lower number of cycles (5.0 vs 7.0) was reported with pembrolizumab + CC-486 vs pembrolizumab + placebo. Overall, pembrolizumab + CC-486 vs pembrolizumab + placebo offered no improvement in PFS. In the pembrolizumab + CC-486 arm, treatment-emergent adverse events were more commonly reported, specifically gastrointestinal, potentially impacting treatment feasibility. Efficacy with pembrolizumab + CC-486 could have been influenced by decreased treatment exposure due to adverse events.