The COAST trial, a randomized phase 2 study, evaluated whether adding novel immunotherapies to durvalumab could improve outcomes for patients with unresectable stage III non–small cell lung cancer (NSCLC) who had completed chemoradiotherapy without progression. Patients received durvalumab alone, durvalumab plus oleclumab (anti-CD73), or durvalumab plus monalizumab (anti-NKG2A).
Updated results showed enhanced activity with both combinations. Objective response rates increased from ~18% with durvalumab alone to ~30% with oleclumab and 35–40% with monalizumab. Progression-free survival (PFS) was notably improved, with 12-month PFS exceeding 60% for durvalumab plus oleclumab versus 34% for durvalumab alone. Overall survival trended higher in the combination arms, though the study was not powered for definitive OS conclusions. Safety profiles were consistent with immune checkpoint therapy; adverse events were more frequent with combinations but generally manageable.
These findings suggest that co-targeting CD73 or NKG2A may deepen immune activation post-chemoradiation. While durvalumab alone remains the standard of care, COAST supports further evaluation in larger trials such as PACIFIC-9 to confirm potential durable survival benefits.