ADRIATIC: A phase III trial of durvalumab ± tremelimumab after concurrent chemoradiation for patients with limited stage small cell lung cancer

Abstract

Background: Limited stage small-cell lung cancer (LS-SCLC), which represents ~30% of newly diagnosed SCLC, remains an area of high unmet medical need. Standard of care, which has not changed for several decades, consists of curative intent platinum-based chemotherapy concurrent with radiotherapy (cCRT) followed by prophylactic brain irradiation (PCI) and observation. Despite good response to cCRT, outcomes remain poor, with median progression-free survival (PFS) ~15 months and overall survival (OS) ~25 months. Durvalumab (D) is a selective, high-affinity, human IgG1 monoclonal antibody (mAb) that blocks programmed cell death ligand-1 binding to programmed cell death-1 and CD80. Tremelimumab (T) is a selective human IgG2 mAb against CTLA-4. D demonstrated a PFS and OS advantage over placebo in locally advanced NSCLC following cCRT. D and D + T demonstrated a tolerable safety profile and antitumour activity in pretreated extensive stage SCLC. The ADRIATIC trial (NCT03703297) will assess if treatment with D ± T is beneficial vs placebo in patients (pts) with LS-SCLC who have not progressed following cCRT.Table67TiPArmDoseInitial regimen (first 4 cycles)Continuation regimen (up to 24 months)D + placebo TD = 1500 mg (intravenous [i.v.])D + placebo T q4wD q4w alone after the final dose of D + placebo TD + T combinationD = 1500 mg (i.v.)T = 75 mg (i.v.)D + T q4wD q4w alone after the final dose of D + TPlacebo D + placebo Ti.v. salinePlacebo D + placebo T q4wPlacebo D q4w Open table in a new tab Trial design: ADRIATIC is a Phase 3, randomised, double-blind, multicentre, placebo-controlled international trial. Pts (N~600) will be randomised 1:1:1 to receive D + placebo T, D + T, or dual placebo, stratified by Stage (I/II vs III) and receipt of PCI at the investigator’s discretion (yes vs no). Eligible pts must have confirmed inoperable Stage I–III LS-SCLC; WHO/ECOG PS 0/1; and completed 4 cycles of cCRT with a response of stable disease or better within 1–42 days prior to randomisation. Pts will receive the assigned treatment until clinical, RECIST v1.1-defined progressive disease, intolerable toxicity or for a maximum of 24 months, whichever comes first. Primary objectives are PFS and OS for D ± T vs placebo. Key secondary endpoints include health-related quality of life, and safety and tolerability. Recruitment is ongoing. Clinical trial identification: NCT03703297. Editorial acknowledgement: Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Craig Turner, MSc, of Cirrus Communications, an Ashfield company (Macclesfield, UK), and was funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca PLC. Funding: AstraZeneca. Disclosure: S. Senan: Departmental research grant: AstraZeneca, Varian Medical Systems, ViewRay Inc.; Advisory boards: AstraZeneca, MSD, Eli Lilly, Celgene. N. Shire: Employment, stock: AstraZeneca, outside the submitted work. G. Mak W. Yao, H. Jiang: Employment, stock: AstraZeneca, outside the conduct of the study.