[HTML][HTML] Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell …
BP Levy, G Giaccone, B Besse, E Felip… - European journal of …, 2019 - Elsevier
European journal of cancer, 2019•Elsevier
Introduction Preclinical and early clinical studies suggest that combining epigenetic agents
with checkpoint inhibitors can potentially improve outcomes in patients with previously
treated advanced non-small cell lung cancer (NSCLC). This phase 2 trial examined second-
line pembrolizumab+ CC-486 (oral azacitidine) in patients with advanced NSCLC. Methods
Patients with one prior line of platinum-containing therapy were randomised in a ratio of 1: 1
to CC-486 or placebo, on days 1–14, in combination with pembrolizumab on day 1 of a 21 …
with checkpoint inhibitors can potentially improve outcomes in patients with previously
treated advanced non-small cell lung cancer (NSCLC). This phase 2 trial examined second-
line pembrolizumab+ CC-486 (oral azacitidine) in patients with advanced NSCLC. Methods
Patients with one prior line of platinum-containing therapy were randomised in a ratio of 1: 1
to CC-486 or placebo, on days 1–14, in combination with pembrolizumab on day 1 of a 21 …
Introduction
Preclinical and early clinical studies suggest that combining epigenetic agents with checkpoint inhibitors can potentially improve outcomes in patients with previously treated advanced non-small cell lung cancer (NSCLC). This phase 2 trial examined second-line pembrolizumab + CC-486 (oral azacitidine) in patients with advanced NSCLC.
Methods
Patients with one prior line of platinum-containing therapy were randomised in a ratio of 1:1 to CC-486 or placebo, on days 1–14, in combination with pembrolizumab on day 1 of a 21-day cycle. The primary end-point was progression-free survival (PFS). Key secondary end-points included overall survival (OS), overall response rate (ORR) and safety.
Results
Among 100 patients randomised (pembrolizumab + CC-486: 51; pembrolizumab + placebo: 49), most were male (57.0%), were white (87.0%) and had Eastern Cooperative Oncology Group performance status 1 (68.0%). No significant difference in PFS was observed between the pembrolizumab + CC-486 and pembrolizumab + placebo arms (median, 2.9 and 4.0 months, respectively; hazard ratio [HR], 1.374; 90% confidence interval [CI], 0.926–2.038; P = 0.1789). Median OS was 11.9 months versus not estimable (HR, 1.375; 90% CI, 0.830–2.276; P = 0.2968); ORR was 20% versus 14%. Median treatment duration was shorter (15.0 versus 24.1 weeks), and the number of cycles was lower (5.0 versus 7.0) with pembrolizumab + CC-486 versus pembrolizumab + placebo. No new safety signals for CC-486 or pembrolizumab were detected. Treatment-emergent adverse events were more common in the pembrolizumab + CC-486 arm, particularly gastrointestinal, potentially impacting treatment feasibility.
Conclusions
No improvement in PFS was observed with pembrolizumab + CC-486 versus pembrolizumab + placebo. Decreased treatment exposure due to adverse events may have impacted efficacy with pembrolizumab + CC-486.
Elsevier