Phase 1-2 trial of canakinumab with chemoradiation and durvalumab consolidation in unresectable stage III NSCLC

Canakinumab is an anti-IL1β monoclonal antibody. The phase 1-2 CHORUS trial at Memorial Sloan Kettering Cancer Center (New York, NY) evaluated canakinumab with concurrent chemoradiotherapy and continued with durvalumab (anti-PD-L1) consolidation for unresectable stage III non-small cell lung cancer (NSCLC). The primary endpoint was progression-free survival (PFS) rate at 24 months from radiotherapy initiation; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Thirty-seven patients received canakinumab, and 32 patients comprised the prespecified efficacy population. At a median follow-up of 25 months, the 24-month PFS rated was 67% (95% CI 52-88), meeting the primary endpoint. Twelve- and 24 OS rate were 93% and 73%, respectively, and the confirmed ORR was 81%. Canakinumab-related grade 3 or 4 events included neutropenia (n=5), febrile neutropenia (n=1), lung infection (n=1), fatigue (n=1) and hypertension (n=1); no canakinumab-related deaths occurred. Pneumonitis of any attribution occurred in 9 of 37 patients (24%; grade 2 in 7; grade 3 in 2). Peripheral immune cell profiling showed attenuated expansion of myeloid-derived suppressor cells and CTLA-4-expressing CD8+ T-cell subsets among responders. Circulating tumor DNA cleared by week 5 in 20 of 30 evaluable patients (67%). The authors conclude that these findings support randomized evaluation of interleukin-1β blockade in this setting.