Phase 2 TIMED trial tests PD‑1/PD‑L1 checkpoint blockade timing (morning vs afternoon).

UNC Lineberger Comprehensive Cancer Center is running this Phase 2, open-label, randomized, parallel-assignment study to test whether time of day changes outcomes from standard immune checkpoint inhibitors in solid tumors. Patients receive standard-of-care PD‑1 and/or PD‑L1 inhibitors (mechanism: blocking PD‑1/PD‑L1 signaling to restore antitumor T‑cell activity) but are randomized to start infusions either before 12:00 PM or after 3:00 PM for the first 4 cycles in metastatic NSCLC, and for 2 neoadjuvant cycles in resectable, locally advanced HNSCC. The NSCLC cohort uses a 2:1 randomization (more patients assigned to one time window), while the HNSCC cohort uses 1:1. The key angle is “chronotherapy” for immuno-oncology—changing scheduling without changing the drug—building on growing clinical literature suggesting earlier-day ICI dosing may correlate with better survival, now tested prospectively. Today’s care is PD‑1/PD‑L1–based regimens (often with chemotherapy) for metastatic NSCLC, and surgery plus radiation/chemoradiation with increasing neoadjuvant/adjuvant PD‑1 use in select resectable HNSCC; this study asks if timing alone can measurably shift PFS/OS (NSCLC) or major pathologic response (HNSCC).