Background: Relapse and death rates for early stage NSCLC remain high despite optimal surgery and adjuvant chemotherapy. We hypothesize that the addition of adjuvant immunotherapy with durvalumab (monoclonal antibody directed against PD-L1) will improve survival.
Methods: This placebo-controlled, randomised, phase 3 trial will recruit 1360 participants, from 15 countries, with completely resected stage IB-IIIA NSCLC, stratified by stage, pre-treatment PDL-1 expression, use of adjuvant chemotherapy, and recruiting centre. Major endpoints include disease free survival in PD-L1 positive participants (primary), and in all participants; overall and lung-cancer-specific survival in PD-L1 positive participants, and all participants; adverse events; quality of life; preferences for adjuvant immunotherapy; and incremental cost effectiveness. Tertiary correlative objectives include assessment of biomarkers as potential prognostic and predictive factors. The study treatment is durvalumab (or placebo) given every 4 weeks continued for 1 year in the absence of disease progression or prohibitive toxicity. The study provides 80% power to detect a hazard ratio (HR) for disease free survival of 0.645 in the PD-L1 positive subgroup (n~530), and a corresponding HR of 0.725 in all participants, with a 1-sided type 1 error rate of 2.5%. Total accrual as of 3 Aug 2018 was 834, with 74 patients enrolled from 26 participating sites in ANZ.
BR31 is an investigator-initiated, cooperative-group trial led by the Canadian Cancer Trials Group (CCTG) in collaboration with ALTG, NHMRC Clinical Trials Centre, IFCT, CEEOG, NCI-Naples, NVALT, KCSG, SLCG, and WJOG; with support from AstraZeneca. Australian New Zealand Clinical Trials Registry: ACTRN 12615000323527.