Multicenter randomized phase 3 trial of impact of time-of-day of immunochemotherapy in treatment-naïve stage IIIC-IV NSCLC

Retrospective studies suggest that early time-of-day (ToD) infusions of immunochemotherapy may improve efficacy. The multicenter phase 3 LungTime-C01 trial in China included 210 patients with treatment naïve stage IIIC-IV non-small cell lung cancer (NSCLC) lacking driver mutations. Patients were randomized 1:1 to either an early or a late ToD group, defined by the administration of the first four cycles of an anti-PD-1 agent before or after 15:00 h. The primary endpoint was progression-free survival (PFS). After a median follow-up of 28.7 months, the median PFS was 11.3 months (95% CI 9.2-13.4) in the early ToD group and 5.7 months (5.2-6.2) in the late ToD group (HR 0.40; p<0.001). The median overall survival was 28.0 months (95% CI NE-NE) in the early ToD group and 16.8 months (13.7-19.9) in the late ToD group (HR 0.42; p<0.001). There were no significant differences between the groups in immune-related adverse events. Early ToD immunochemotherapy was associated with enhanced antitumor CD8⁺ T cell characteristics compared with late ToD treatment. The authors conclude that this study indicates that early ToD immunochemotherapy substantially improves PFS and OS of patients with treatment-naïve stage IIIC-IV NSCLC.