A randomized phase III trial of concurrent chemoradiotherapy followed by durvalumab consolidation, with or without induction chemo-immunotherapy, in patients with unresectable locally advanced non-small cell lung cancer: JCOG2510 (PRIME-CRT)

Background Definitive concurrent chemoradiotherapy (cCRT) followed by durvalumab consolidation is the current standard of care for unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). However, survival outcomes in this setting remain unsatisfactory. Although the PACIFIC trial improved outcomes, further intensification of systemic therapy may be required to improve long-term survival. Preclinical and perioperative clinical evidence suggests that introducing immunotherapy in the presence of an intact primary tumor may enhance antitumor immune responses. Recently, early-phase studies have reported the feasibility and potential efficacy of induction chemo-immunotherapy followed by cCRT; however, its clinical benefit has not been confirmed in a phase III trial. Patients and Methods This multicenter, randomized, phase III trial is designed to determine whether the addition of induction chemo-immunotherapy to the current standard strategy of cCRT followed by durvalumab consolidation improves survival outcomes in patients with unresectable LA-NSCLC. Previously untreated patients with unresectable LA-NSCLC without activating EGFR mutations are randomized 1:1 to receive either cCRT followed by durvalumab consolidation or induction chemo-immunotherapy followed by cCRT and durvalumab consolidation. Randomization is adjusted for age, clinical stage, programmed death-ligand 1 expression, and institution. The primary endpoints are progression-free and overall survival. Secondary endpoints include objective response rate, proportion of patients proceeding to cCRT after induction therapy, and adverse events. A total of 212 patients will be enrolled from 60 institutions over five years. Conclusion The results of this trial should clarify whether the addition of induction chemo-immunotherapy can enhance curative potential and lead to improved overall survival in patients with unresectable LA-NSCLC.