215TiP A phase II study of durvalumab (MEDI 4736) maintenance in frail limited disease small cell lung cancer patients after thoracic chemo-radiotherapy (CRT): DURVALUNG trial

Small cell Lung Cancer (SCLC) is a rare tumour subtype, and approximately one third of the SCLC patients (pts) present limited disease (LD-SCLC) with a 5-year survival rate between 20% and 25%. The standard of care (SOC) is platinum-based chemotherapy combined with etoposide and thoracic radiotherapy (CRT). While immunotherapy is currently limited to advanced SCLC setting, NSCLC setting suggest that the combination of immunotherapy and radiotherapy may produce a synergistic effect. The relevance of a multimodal strategy including immunotherapy after CRT is therefore currently under investigation, but frail LD-SCLC pts are often excluded from clinical trials. Thus, DURVALUNG study aims to evaluate the efficacy of durvalumab maintenance specifically in frail LD-SCLC pts who have not progressed following concomitant or sequential CRT. DURVALUNG is an academically-lead, open-label, multicentre, randomized phase II trial in previously untreated frail LD-SCLC pts. Pts will be screened during the CRT and only those achieving a disease control (SD or PR/CR) after the CRT and presenting frail condition (ECOG PS 2, ECOG PS 0-1 and older than 70 or did not receive a concomitant CRT due to comorbidities) will be randomized 1:1 to receive durvalumab every 4 weeks for 24 months or surveillance as per SOC. Prophylactic Cranial Irradiation will be allowed according to local SOC within 45 days after the end of CRT. 110 pts will be randomized in the study. A safety interim analysis will be performed after the first 15 pts included into the experimental arm for the Data Safety Monitoring Board. The main objective is to evaluate the progression-free survival (PFS), per investigator, of LD-SCLC pts on durvalumab arm compared to surveillance. The primary endpoint analysis will be a Cox regression analysis with 90% confidence interval (1-sided). Secondary objectives are BIRC PFS, overall survival, quality of life, and toxicity. Ancillary studies will be conducted to determine biomarkers of clinical benefit from the durvalumab maintenance, the impact of sarcopenia on outcomes, and the correlation between radiotherapy plan and survival outcomes and toxicities. EudraCT: 2021-005920-39 NCT05617963. Unicancer. AstraZeneca.